DEPT OF PSYCHIATRY



Researcher : Chan CY
List of Research Outputs

Chan C.Y., Lee A.M., Lam S.K., Leung K.Y., Chung K.F., Koh Y.W. and Tang C.S.K., Psychological abuse experiences are independently associated with disordered eating symptoms among pregnant women, Paper presented at the Hong Kong Psychological Society Annual Conference 2010 "Development challenges across Life Stages", Hong Kong, June 12, 2010.
Koh Y.W., Lee A.M., Leung K.Y., Chan C.Y., Tang C.S.K. and Chung K.F., Identifying Psychosocial Risk Factors for Mental Health and Psychosomatic Problems Among Expectant Fathers During Transition to Fatherhood, Paper presented at the American Psychological Science Annual Convention, Boston, May 27-30, 2010.


Researcher : Chan KKS
List of Research Outputs

Chan K.K.S., Hui C.L.M., Chiu C.P.Y., Lam M.L.M., Chan K.W., Lin J., Xu J., Tang Y.M., Wong G.H.Y., Longenecker J.M. and Chen E.Y.H., A 3-year prospective study of spontaneous eye-blink rate in first-episode schizophrenia: Relationships with neurocognitive functions and relapse, 2nd Schizophrenia International Research Society Conference (April 10-14, 2010), Florence, Italy. 2010.
Chan K.K.S., Wong G.H.Y., Hui C.L.M., Tang Y.M., Chan K.W., Lam M.L.M., Chiu C.P.Y. and Chen E.Y.H., Game Theoretical Approach to Theory of Mind Deficits in Schizophrenic Patients with Delusion(s) of Reference, Schizophrenia Research. 2010, 117 (2-3): 286.
Chan K.W., Chiu C.P.Y., Lam M.L.M., Hui C.L.M., Wong G.H.Y., Tang Y.M., Chan K.K.S. and Chen E.Y.H., Relationship of neurocognitive function and impairment of insight in first episode schizophrenia, Schizophrenia Research. 2010, 117 (2-3): 209.
Cheung V., Chiu C.P.Y., Law C.W., Cheung C., Hui C.L.M., Chan K.K.S., Sham P.C., Deng Y., Tai K.S., Khong P.L., McAlonan G.M., Chua S.E. and Chen E.Y.H., Positive symptoms and white matter microstructure in never-medicated first episode schizophrenia, Psychological Medicine. 2010, 40: 1-12.
Tang Y.M., Chiu C.P.Y., Hui C.L.M., Chan K.K.S., Lam M.L.M., Chan K.W., Wong G.H.Y. and Chen E.Y.H., Clinical and cognitive correlates of perceived extent of recovery in Chinese patients with psychosis, Schizophrenia Research. 2010, 117 (2-3): 516.


Researcher : Chan KW
Project Title:fMRI investigation of self-relevance in schizophrenia patients
Investigator(s):Chan KW, Chen EYH, Chiu CPY, Lam MLM, Hui CLM, Wong GHY
Department:Psychiatry
Source(s) of Funding:Seed Funding Programme for Basic Research
Start Date:12/2009
Abstract:
Project objective: 1. To identify the role of cortical midline structure of the brain in the self-relevance task in patients with schizophrenia. 2. To investigate the differential role of cortical midline structure of the brain at resting state and with self-relevance task. Key issues and problems being addressed: Study of the sense of self has long been one of the focuses in philosophy and psychology. Since very early days of schizophrenia descriptions, the anomalies of the sense of self have been considered as the fundamental or core feature (Parnas & Sass, 2001; Sass & Parnas, 2003) Base on phenomenological perspective, Parnas (2003) identified three levels of selfhood. First, there is the pre-reflective level, which refers to a first-person giveness of experience - the implicit awareness that this is ‘my’ experience. This is sometimes referred to as the ‘basic’ self or as ‘ipseity’ (Sass & Parnas, 2003; Zahavi, 2005). Both second and third levels are more complex reflective self. The second level refers to an explicit awareness of the self as an invariant and persisting subject of experience of action and it presupposes the more basic first level. The final level is the social or narrative self, which refers to individual characteristics. From the neurobiological perspective, the selfhood can be identified into two levels. The first ‘proto-self’ refers pre-reflective core self and can be considered as equivalent to the first phenomenological level. The second one is the ‘autobiographical self’, which refers to a higher cognitive processing and the concept is aligned with the reflective levels defined by the phenomenologists (Northoff, et al., 2006). It is suggested that the disorder of self occurs at the first or most basic, pre-reflective level of self-awareness in the schizophrenia-spectrum disorders (Parnas & Handest, 2003; Sass & Parnas, 2003). Our normal human experiences rely on a sense of being absorbed in a word of objects and this provides us with a sense of ‘inhabiting’ our self in a pre-reflective or automatic fashion. This refers to as ‘presence’. This sense of ‘presence’ or basic self-awareness act as the background upon which explicit or objectifying conscious activity takes place. The lost of this sense, which tends to involve hyper-reflexive awareness of aspects of thought and bodily perception that would normally be as the background and implicit, this then evolve into delusions. In this evolution, the ‘as if’ component of the anomalous experiences at the early stage of psychosis is lost, and these experiences ‘crystallise’ into delusions. Hyper-reflexivity is therefore a form of exaggerated self-consciousness and heightened awareness of aspects of one’s experience. With the technique of neuroimaging, neuroscientists have been looking into various brain regions in association with the self-related tasks and the concept of ‘self’, with a hope to further our knowledge of the neurobiological basis of schizophrenia-spectrum disorder or psychosis. In a recent meta-analysis of the imaging studies in healthy subjects, Northoff et al (2006) concluded that the cortical midline structures (CMS) are activated during tasks about self-relevance of stimuli, irrespective of the stimulus domain or sensory modality. The CMS includes medial orbital prefrontal cortex, the ventromedial prefrontal cortex, the anterior cingular cortex, the dorsomedial prefromtal cortex, the medial parietal cortex, the posterior cingulate cortex and retrosplenial cortex. The authors have further identified three regional clusters within CMS, which can be characterized as ventral, dorsal and posterior, associated with different domains of self. However, many of the fMRI paradigms studied in this meta-analysis required consciously directed appraisals about the self-relatedness of stimuli. Therefore they are possibly more corresponding to the narrative and reflective self than the pre-reflective core self. On the other hand, it was argued that these self-relevance tasks require process of an experience of self and such sense of experience can be referred to pre-reflective self. Thus it can be argued that the CMS regions play a pre-reflective role in self-referential processing during task though the evidence is indirect. Another indirect evidence is that the studies of resting state brain condition have found increase metabolic activation of the same midline cortical regions during the resting-state, while having relatively reduced activity during performance of cognitively demanding, non self-referential tasks (Gusnard, Akbudak, Shulman, & Raichle, 2001; Raichle, et al., 2001). This implies a shift of self-focus to outward focus and hence a function of CMS in self-relevancy process. Several functional imaging studies of patients with schizophrenia have reported evidence of altered CMS function during both the resting state and performance of cognitive tasks (Garrity, et al., 2007; Harrison, Yücel, Pujol, & Pantelis, 2007; Zhou, et al., 2007). The functional imaging studies of patients with schizophrenia using tasks involving self-monitoring and source memory have all implicated the important role of CMS and their disruption in psychosis. However, few studies have looked into the specific role of various CMS regions comparing resting state and self-referential process directly. There is even more limited study in patient groups. The evidence in differentiating the role of different regions of CMS and particularly the associated region for the pre-reflective self, which was believed to possibly reflect the fundamental features of schizophrenia, particularly positive symptoms such as delusions is also lacking. In a functional imaging study of schizophrenic patients with delusion, Blackwood et al (2004) reported hyperactivity of posterior cingulate region of deluded subjects while they are processing ambiguously self-relevant conditions compare to control. In fact Damasio (2003) suggested the cigulate gyrus as the key region in a neural network sustaining the core self or pre-reflective self. It is therefore possible that processing the ambiguous self-relevant condition can reveal more clearly the disturbance of the core self of the deluded patients. In order to examine this hypothesis and further our understanding about the differential role of CMS during the resting state and self-relevancy process, the current functional imaging study will use a modified version of the task developed in the study reported by Blackwood et al (2004), and compare the differential activation of CMS regions during the task and the resting state of both patient and control groups.


Project Title:2nd Biennial Schizophrenia International Research Society Conference Relationship of neurocognitive function and impairment of insight in first episode schizophrenia
Investigator(s):Chan KW
Department:Psychiatry
Source(s) of Funding:URC/CRCG - Conference Grants for Teaching Staff
Start Date:04/2010
Completion Date:04/2010
Abstract:
N/A


Project Title:A 10-year outcome study of an early intervention program for psychosis in Hong Kong (EASY) compare with standard care service
Investigator(s):Chan KW, Chen EYH, Lam MLM, Chiu CPY
Department:Psychiatry
Source(s) of Funding:Commissioned Research on Mental Health Policy and Services
Start Date:06/2010
Abstract:
To evaluate the 10-year clinical and functional outcome of patients with first episode of schizophrenia spectrum disorder who were in the early intervention (EI) service and compare that with a controlled cohort who received standard care (SC) service.


List of Research Outputs

Anderson J., Chan K.W., Walsh C. and London M., Methadone prescribing in the general hospital, Clinical Governance: An International Journal. 2010, 15 (1): 12-18.
Chan K.K.S., Hui C.L.M., Chiu C.P.Y., Lam M.L.M., Chan K.W., Lin J., Xu J., Tang Y.M., Wong G.H.Y., Longenecker J.M. and Chen E.Y.H., A 3-year prospective study of spontaneous eye-blink rate in first-episode schizophrenia: Relationships with neurocognitive functions and relapse, 2nd Schizophrenia International Research Society Conference (April 10-14, 2010), Florence, Italy. 2010.
Chan K.K.S., Wong G.H.Y., Hui C.L.M., Tang Y.M., Chan K.W., Lam M.L.M., Chiu C.P.Y. and Chen E.Y.H., Game Theoretical Approach to Theory of Mind Deficits in Schizophrenic Patients with Delusion(s) of Reference, Schizophrenia Research. 2010, 117 (2-3): 286.
Chan K.W., Beyond Medication: Therapeutic Engagement and the Recovery from Psychosis, Psychological Medicine. 2010, 40 (8): 1408.
Chan K.W., Dudas R., Tzur M., Adapa R., Bhatia A., Absalom A.R., Corlett P.R., Bullmore E.T., Fletcher P.C. and Honey G.D., Comparison of pharmacological psychosis - Ketamine and delta-9-tetrahydrocannabinol, CIPN World Congress Hong Kong, June 6-10, 2010.
Chan K.W., Chiu C.P.Y., Lam M.L.M., Hui C.L.M., Wong G.H.Y., Tang Y.M., Chan K.K.S. and Chen E.Y.H., Relationship of neurocognitive function and impairment of insight in first episode schizophrenia, Schizophrenia Research. 2010, 117 (2-3): 209.
Chan K.W., 思覺失調的(關鍵時期), 醫學教室, Apple Daily (2010-6-23). 2010.
Tang Y.M., Chiu C.P.Y., Hui C.L.M., Chan K.K.S., Lam M.L.M., Chan K.W., Wong G.H.Y. and Chen E.Y.H., Clinical and cognitive correlates of perceived extent of recovery in Chinese patients with psychosis, Schizophrenia Research. 2010, 117 (2-3): 516.
Tang Y.M., Wong G.H.Y., Hui C.L.M., Lam M.L.M., Chiu C.P.Y., Chan K.W., Chung D.W.S., Tso S., Chan K.P.M., Yip K.C., Hung S.F. and Chen E.Y.H., Early intervention for psychosis in Hong Kong - the EASY programme, Early Intervention in Psychiatry. 2010, 4 (3): 214-219.
Wong G.H.Y., Tao H.J., He Z., Liu H.H., Chiu C.P.Y., Chan K.W., Lam M.L.M., Hui C.L.M., Tang Y.M., Wang Y.H., Xue Z.M., Liu Z.N. and Chen E.Y.H., Delusions of reference, excessive top-down processing, and default mode network in first-episode schizophrenia, Schizophrenia Research. 2010, 117 (2-3): 491.


Researcher : Chan MSH
List of Research Outputs

Chan M.S.H., Wong N.M., Kong A.Y.F., Lam T.P., Wun Y.T. and Tam W.W.S., A new reference PEFR nomogram for Hong Kong Chinese. (Letter), The Hong Kong Practitioner. 2009, 31: 106-107.
Chan M.S.H., Wong N.M., Kong A.Y.F., Wun Y.T., Lam T.P. and Tam W.W.S., The PEFR and normogram in Hong Kong Chinese, 2010 Four Parties Conference on Family Medicine, Beijing. 2010.
Wun Y.T., Chan M.S.H., Wong N.M., Kong A.Y.F., Tam W.W.S. and Lam T.P., A Study of Peak Expiratory Flow Rate In Hong Kong School Children, The Hong Kong College of Family Physicians Annual Scientific Meeting 2010.


Researcher : Chan RCK
List of Research Outputs

Hu Z.Y., Chan R.C.K. and McAlonan G.M., Maturation of social attribution skills in typically developing children: An investigation using the Social Attribution Task and a modified version for young children., Behavioral and Brain Functions. 2010, in press.
So H.C., Fong P.Y., Chen R.Y.L., Hui T.C.K., Ng M.Y.M., Cherny S.S., Mak W.W., Cheung E.F.C., Chan R.C.K., Chen E.Y.H., Li T. and Sham P.C., Identification of Neuroglycan C and Interacting Partners as Potential Susceptibility Genes for Schizophrenia in a Southern Chinese Population, American Journal of Medical Genetics Part B (Neuropsychiatric Genetics). 2010, 153B (1): 103-113.


Researcher : Chen EYH
Project Title:10th Biennial Winter Workshop on Schizophrenia N400 and P600 Event-Related Potential Responses to Neutral and Affect-laden Semantic Stimulus in Schizophrenic Patients 2) Predictors of Short-term Functional Outcome Following First Episode Psychosis 3) spontaneous Blink Rate in First-episode Schi Predictors of Short-term Functional Outcome Following First Episode Psychosis Spontaneous Blink Rate in First-episode Schizophrenic Patients: a Prospective Follow-up Study and Temporal Evolution of Extra-pyramidal Side-effects to Conventional Anti-psychotic Medications in First-episode Psychosis
Investigator(s):Chen EYH
Department:Psychiatry
Source(s) of Funding:URC/CRCG - Conference Grants for Teaching Staff
Start Date:02/2000
Abstract:
N/A


Project Title:2nd European Conference on Schizophrenia Research Assessing the efficacy of relapse prevention in single episode psychosis patients with stable maintenance treatment for at least one year: A double-blind randomized placebo controlled trial
Investigator(s):Chen EYH
Department:Psychiatry
Source(s) of Funding:URC/CRCG - Conference Grants for Teaching Staff
Start Date:09/2009
Abstract:
N/A


List of Research Outputs

Bowden C.L., Mosolov S., Hranov L., Chen E.Y.H., Habil H., Kongsakon R., Manfredi R. and Lin H.N., Efficacy of valproate versus lithium in mania or mixed mania: a randomized, open 12-week trial, International Clinical Psychopharmacology Journal. 2010, 25 (2): 60-67.
Chan K.K.S., Hui C.L.M., Chiu C.P.Y., Lam M.L.M., Chan K.W., Lin J., Xu J., Tang Y.M., Wong G.H.Y., Longenecker J.M. and Chen E.Y.H., A 3-year prospective study of spontaneous eye-blink rate in first-episode schizophrenia: Relationships with neurocognitive functions and relapse, 2nd Schizophrenia International Research Society Conference (April 10-14, 2010), Florence, Italy. 2010.
Chan K.K.S., Wong G.H.Y., Hui C.L.M., Tang Y.M., Chan K.W., Lam M.L.M., Chiu C.P.Y. and Chen E.Y.H., Game Theoretical Approach to Theory of Mind Deficits in Schizophrenic Patients with Delusion(s) of Reference, Schizophrenia Research. 2010, 117 (2-3): 286.
Chan K.W., Chiu C.P.Y., Lam M.L.M., Hui C.L.M., Wong G.H.Y., Tang Y.M., Chan K.K.S. and Chen E.Y.H., Relationship of neurocognitive function and impairment of insight in first episode schizophrenia, Schizophrenia Research. 2010, 117 (2-3): 209.
Chang W.C., Tang Y.M., Chiu C.P.Y., Hui C.L.M., Lam M.L.M., Wong G.H.Y., Law C.W., Tso S., Chan K., Hung S.F., Chung D.W.S. and Chen E.Y.H., Gender differences in patients presented with first-episode psychosis in Hong Kong, Schizophrenia Research. 2010, 117 (2-3): 281-2.
Chen E.Y.H., Associate Editor, Early Intervention in Psychiatry. 2010.
Chen E.Y.H., Editorial Board (2003-present), Schizophrenia Research. 2010.
Chen E.Y.H., Editorial Board (2005-present), Chinese Medicial Journal. 2010.
Chen E.Y.H., Editorial Board (2006-present), Early Intervention in Psychiatry. 2010.
Chen E.Y.H., Editorial Board (2009), Clinical Psychopharmacology and Neuroscience. 2010.
Chen E.Y.H., Editorial Board Member, Clinical Psychopharmacology and Neuroscience (2009). 2009.
Chen E.Y.H., Executive Committee Member, International Association of Neuropsychiatry. 2010.
Chen E.Y.H., International Advisory Council, Schizophrenia International Research Society. 2010.
Chen E.Y.H., Hui C.L.M., Lam M.L.M., Chiu C.P.Y., Law C.W., Chung D.W.S., Tso S., Pang E.P.F., Chan K.T., Wong Y.C., Mo F.Y.M., Chan K.P.M., Yao T.J., Hung S.F. and Honer W.G., Maintenance treatment with quetiapine versus discontinuation after one year of treatment in patients with remitted first episode psychosis: randomised controlled trial, British Medical Journal. 2010, 341: c4024.
Chen E.Y.H., Member, Publications Committee of the SIRS (Schizophrenia International Research Society) (2010-2012). 2010.
Chen E.Y.H., Hui C.L.M., Dunn E.L.W., Miao M.Y.K., Yeung W.S., Wong C.K., Chan W.F. and Tang W.N., Normalization of semantic categorization deficit in first-episode schizophrenia patients following symptomatic recovery: a three-year prospective longitudinal study, Schizophrenia Research. 2010, 117 (2-3): 292-293.
Chen E.Y.H., President, Asian Network for Early Psychosis. 2010.
Chen E.Y.H., Publication Committee, Schizophrenia International Research Society. 2010.
Chen E.Y.H., Vice President (Asia Pacific), by election, International Early Psychosis Association (membership >2000). 2010.
Cheung V., Chiu C.P.Y., Law C.W., Cheung C., Hui C.L.M., Chan K.K.S., Sham P.C., Deng Y., Tai K.S., Khong P.L., McAlonan G.M., Chua S.E. and Chen E.Y.H., Positive symptoms and white matter microstructure in never-medicated first episode schizophrenia, Psychological Medicine. 2010, 40: 1-12.
Deng Y., McAlonan G.M., Cheung C., Chiu C.P.Y., Law C.W., Cheung V., Sham P.C., Chen E.Y.H. and Chua S.E., A naturalistic study of grey matter volume increase after early treatment in anti-psychotic naïve, newly diagnosed schizophrenia, Psychopharmacology. 2009, 206: 437-446.
Honer W.G., Procyshyn R.M., Chen E.Y.H., MacEwan G.W. and Barr A.M., A translational research approach to poor treatment response in patients with schizophrenia: clozapine-antipsychotic polypharmacy, Journal of Psychiatry Neuroscience. 2009, 34 (6): 433-442.
Hui C.L.M., Chen E.Y.H., Dunn E.L.W., Miao M.Y.K., Yeung W.S., Wong C.K., Chan W.F. and Tang W.N., The association between semantic categorization deficit and symptoms in first-episode schizophrenia, Schizophrenia Research. 2010, 117 (2-3): 409-410.
Lam M.L.M., Pearson V., Ng R.M.K., Chiu C.P.Y., Law C.W. and Chen E.Y.H., What does recovery from psychosis mena? Perceptions of young first-episode patients, International Journal of Social Psychiatry. 2010, 2-9.
Liu H.H., Kaneko Y., Ouyang X., Li L., Hao Y.H., Chen E.Y.H., Jiang T., Zhou Y. and Liu Z.N., Schizophrenic Patients and Their Unaffected Siblings Share Increased Resting-State Connectivity in the Task-Negative Network but Not Its Anticorrelated Task-Positive Network, Schizophrenia Bulletin. 2010, 1-10.
Ng R.M.K., Pearson V., Chen E.Y.H. and Law C.W., What does recovery from schizophrenia mean? Perceptions of medical students and trainee psychiatrists, International Journal of Social Psychiatry. 2010, 1-16.
Ran M.S., Chan C.L.W., Chen E.Y.H., Mao W.J., Hu S.H., Tang C.P., Lin F.R. and Conwell Y., Differences in mortality and suicidal behaviour between treated and never-treated people with schizophrenia in rural China, The British Journal of psychiatry. 2009, 195 (2): 126-131.
So H.C., Chen R.Y.L., Chen E.Y.H., Cheung E.F.C., Cherny S.S. and Li T., Genome-wide association study of schizophrenia in a Chinese population, Poster presented at the 59th Annual Meeting of the American Society of Human Genetics, Honolulu, Hawaii, USA, October 22, 2009.
So H.C., Fong P.Y., Chen R.Y.L., Hui T.C.K., Ng M.Y.M., Cherny S.S., Mak W.W., Cheung E.F.C., Chan R.C.K., Chen E.Y.H., Li T. and Sham P.C., Identification of Neuroglycan C and Interacting Partners as Potential Susceptibility Genes for Schizophrenia in a Southern Chinese Population, American Journal of Medical Genetics Part B (Neuropsychiatric Genetics). 2010, 153B (1): 103-113.
Tang Y.M., Chiu C.P.Y., Hui C.L.M., Chan K.K.S., Lam M.L.M., Chan K.W., Wong G.H.Y. and Chen E.Y.H., Clinical and cognitive correlates of perceived extent of recovery in Chinese patients with psychosis, Schizophrenia Research. 2010, 117 (2-3): 516.
Tang Y.M., Wong G.H.Y., Hui C.L.M., Lam M.L.M., Chiu C.P.Y., Chan K.W., Chung D.W.S., Tso S., Chan K.P.M., Yip K.C., Hung S.F. and Chen E.Y.H., Early intervention for psychosis in Hong Kong - the EASY programme, Early Intervention in Psychiatry. 2010, 4 (3): 214-219.
Tang Y.M., Lam M.L.M., Wong H.Y., Hui C.L.M., Chiu C.P.Y., Law C.W., Chung D.W.S., Tso S., Yip K.C., Chen E.Y.H. and Hung S.F., Time to a stop or a change in prescription of initial antipsychotic medication in first-episode schizophrenic patients: A naturalistic study, 2nd Schizophrenia International Research Society Conference (April 10-14, 2010), Florence, Italy. 2010.
Wong G.H.Y., Tao H.J., He Z., Liu H.H., Chiu C.P.Y., Chan K.W., Lam M.L.M., Hui C.L.M., Tang Y.M., Wang Y.H., Xue Z.M., Liu Z.N. and Chen E.Y.H., Delusions of reference, excessive top-down processing, and default mode network in first-episode schizophrenia, Schizophrenia Research. 2010, 117 (2-3): 491.


Researcher : Chen RYL
List of Research Outputs

So H.C., Chen R.Y.L., Chen E.Y.H., Cheung E.F.C., Cherny S.S. and Li T., Genome-wide association study of schizophrenia in a Chinese population, Poster presented at the 59th Annual Meeting of the American Society of Human Genetics, Honolulu, Hawaii, USA, October 22, 2009.
So H.C., Fong P.Y., Chen R.Y.L., Hui T.C.K., Ng M.Y.M., Cherny S.S., Mak W.W., Cheung E.F.C., Chan R.C.K., Chen E.Y.H., Li T. and Sham P.C., Identification of Neuroglycan C and Interacting Partners as Potential Susceptibility Genes for Schizophrenia in a Southern Chinese Population, American Journal of Medical Genetics Part B (Neuropsychiatric Genetics). 2010, 153B (1): 103-113.


Researcher : Cherny SS
Project Title:Variance components models for mapping QTLs
Investigator(s):Cherny SS, Sham PC
Department:Psychiatry
Source(s) of Funding:National Institutes of Health, US Department of Health and Human Services - General Award
Start Date:09/2006
Abstract:
To develop novel statistical methods and software for linkage and association mapping of complex traits.


Project Title:Genome-wide association mapping of epilepsy using DNA pooling
Investigator(s):Cherny SS, Sham PC
Department:Psychiatry
Source(s) of Funding:Seed Funding Programme for Basic Research
Start Date:04/2008
Completion Date:03/2010
Abstract:
In recent years, the contribution of genetic mutations or variants to the pathogenesis of epilepsy has been increasingly recognized. A number of rare familial epilepsy syndromes caused by single gene mutations have been identified, mostly (but not exclusively) including those of the ion channels involved in neuronal excitation (Gurnett & Hedera, Arch Neurol, 64:324-8, 2007; Steinlein, Nat Rev Neurosci, 5: 400-8, 2004). Examples include generalised epilepsy with febrile seizures associated with mutations of voltage-gated sodium channel subunit genes (SCN1A, SCN2A, SCN1B) and a GABAA receptor subunit gene (GABRG2), benign nocturnal familial convulsions with mutations of potassium channel genes KCNQ2 or KCNQ3, autosomal dominant nocturnal frontal lobe epilepsy with mutations in a neuronal nicotinic acetylcholine receptor (CHRNA4 or CHRNB2), and familial lateral temporal lobe epilepsy with LGI1 (leucine-rich glioma inactivated gene 1). Although the list of putative gene mutations is expanding, they represent only a very small fraction of all epilepsies. For the majority of patients, their epilepsies are thought to be complex disorders with multiple susceptibility genes interacting with various environmental factors. There have been recent attempts to identify the genetic susceptibility for these common epilepsy syndromes using association studies of candidate genes. The candidate genes were selected largely based on the current understanding of the pathobiology that underlies epileptogenicity or seizure propagation, as well as on their role in the monogenic epilepsy syndromes. Thus they have mostly included the voltage gated ion channels, GABA receptor subunits, but also genes involved in inflammatory response (e.g., interleukin 1ß). Overall, their results have been disappointing. In a comprehensive review of over 50 such studies, it was concluded that ``no consistent or convincing susceptibility genes have emerged'' (Tan et al, Epilepsia, 45:1429-42, 2004). Possible reasons for this include methodological and statistical shortcomings (e.g., small sample size, inappropriate selection of controls, population stratification). Unfortunately, the situation has not significantly improved since this review was published. However, failure to identify susceptibility genes using a candidate gene approach might also be because our understanding of the pathogenesis of seizure generation and propagation, and how drugs modulate these processes, remains rudimentary. For instance, the dogmatic view of an exclusive neuronal involvement in seizure genesis has been challenged by the recent discovery that astrocytes may also play a key role in seizure activity and several antiepileptic drugs might act, at least in part, by suppressing astrocytic intracellular Ca2+ signaling (Tian et al, Nat Med, 11:973-81, 2005). This argues for the adoption of a genome-wide association approach without a priori assumptions, which has the potential to discover previously unsuspected markers and to shed much needed insights into the epileptogenic process (Hirschhorn & Daly, Nat Rev Genet, 6:95-108, 2005). The success of this approach has been demonstrated in the discovery of genes or loci implicated in pathogenesis of common diseases in other disciplines (e.g., breast cancer, diabetes) that were never suspected previously to be involved in the disease of interest (Wellcome Trust Case Control Consortium, Nature, 447:661-78, 2007). In addition, the recent advances in detecting copy number variations (CNVs) of genetic material lying both within and outside of genes has led to further findings that CNVs can be involved with disease occurrence and drug response (Redon et al, Nature, 444:444-54, 2006; Stranger et al, Science, 315:848-53, 2007). Using array-based comparative genomic hybridization (array-CGH), Kim et al (Brain Dev, 2007) studied DNA samples from 60 patients with idiopathic generalized epilepsy, partial epilepsy and febrile seizures. They identified chromosomal aberrations of both gains and losses, which might be genomic regions with epilepsy-related genes. Previous association studies have tended to focus on idiopathic epilepsy syndromes which largely develop in children and are generally responsive to treatment. Little attention, however, has been paid to the symptomatic epilepsies, despite the fact that the same CNS insult may result in chronic epilepsy in one individual but not in another, suggesting genetic influence. Unlike idiopathic epilepsy syndromes, symptomatic epilepsies can develop in all ages, and are more often (up to 40%) resistant to drug treatment. Therefore, revealing etiology and thus possible new modes of treatment is even more important for symptomatic than for idiopathic epilepsy. Previous association studies have also tended to investigate candidate single nucleotide polymorphisms (SNPs) individually or in haplotype structures. These SNPs were often selected based on the current understanding of the pathobiology that underlies epileptogenicity or seizure propagation, which remains rudimentary. The associations, if any, found in these studies have been weak and have not been replicated in independent cohorts. Identifying disease susceptibility genetic polymorphisms by a genome-wide association (GWA) approach without a priori assumptions has the potential to discover previously unsuspected markers and to shed much needed insights into the epileptogenic process. Further work would be needed to relate any disease susceptibility single nucleotide polymorphisms identified to specific molecular functional pathways to facilitate translation into clinical practice. In this project, we propose to identify the disease susceptibility genetic markers in patients with the three different classes of epilepsy, using a two-stage genome-wide association (GWA) approach involving DNA pooling in the first phase, which reduces costs dramatically. The funding requested in the present proposal is for genotyping of pooled DNA samples for the first-phase of this two-stage study, with stage two funding to be requested from RGC in October 2008. We propose to genotype 30 pools of DNA on the Affymetrix Genome-Wide Human Mapping Array 6.0, with 50 epilepsy cases or controls in each pool, thereby resulting in genetic analysis of 1500 individuals. Our specific objectives are: (1) to identify marker loci which predict increased susceptibility to idiopathic and symptomatic epilepsy by (2) forming 30 pools of 50 samples each of DNA obtained from 500 idiopathic and 500 symptomatic epileptics, along with 500 unaffected controls. (3) Drug drug responsive and drug resistant patients will be grouped into separate pools, allowing exploration of genetic markers that predict response to different classes of antiepileptic drugs. (4) We will conduct a GWA scan using these pooled samples to identify single SNPs and/or CNVs associated with increased risk of epilepsy syndromes, using the Affymetrix Genome-Wide Human SNP Array 6.0, which contains over 900,000 SNP markers and over 900,000 CNV markers.


Project Title:Genome-wide association mapping of susceptibility loci for symptomatic epilepsy
Investigator(s):Cherny SS, Sham PC
Department:Psychiatry
Source(s) of Funding:General Research Fund (GRF)
Start Date:01/2009
Abstract:
(1) To identify marker loci which predict increased susceptibility to epilepsy by conducting a genome-wide association (GWA) scan to identify single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) associated with increased risk of symptomatic epilepsy syndromes in a cohort of 360 symptomatic Chinese patients compared with 360 normal population controls (to be available as a shared resource for Hong Kong GWA studies), using the Illumina Human610Quad platform; (2) To explore genetic markers that predict response to different classes of antiepileptic drugs, using data already obtained on drug responsiveness; (3) Findings of the study will form the basis for "in silico" and functional analysis of the candidate regions identified, to both identify the genes causing epilepsy and understand their function.


Project Title:59th Annual Meeting of the American Society of Human Genetics Fine mapping of Hirschsprung disease loci in 9q31
Investigator(s):Cherny SS
Department:Psychiatry
Source(s) of Funding:URC/CRCG - Conference Grants for Teaching Staff
Start Date:10/2009
Completion Date:10/2009
Abstract:
N/A


Project Title:Genotype by risk factor interactions in cognitive decline: The Guangzhou Biobank Cohort Study
Investigator(s):Cherny SS, Jiang CQ, Lam TH, Law ACK, Sham PC
Department:Psychiatry
Source(s) of Funding:General Research Fund (GRF)
Start Date:01/2010
Abstract:
1) To explore behavioral, demographic, environmental, medical, psychological, and clinical risk factors for cognitive decline in the Guangzhou Biobank Cohort Study; 2) To examine the impact of known genetic risk variants for Alzheimer's disease on cognitive decline in the GBCS by; 3) Indentifying the individuals whose 10-word recall has declined the most over a 4-year period along with those individuals whose 10-word recall is diagnostic of dementia (a total of 720 people), in addition to 720 individuals with no sign of cognitive decline; 4) Genotyping the 28 genetic variants most likely associated with Alzheimer's disease according to the AlzGene database; 5) Examining interactions between the genetic risk variants and clinical, behavioral, environmental, and other risk factors for cognitive decline; 6) Examining epistatic interactions among pairs or sets of risk genes.


Project Title:Exon sequencing of Semaphorin, a novel Hirschsprung's Disease susceptibility locus
Investigator(s):Cherny SS, Tam PKH, Garcia-Barcelo MM, Sham PC
Department:Psychiatry
Source(s) of Funding:Seed Funding Programme for Basic Research
Start Date:03/2010
Abstract:
The primary pathology of Hirschsprung's Disease (HSCR) is the absence of enteric ganglion cells in variable lengths of the hindgut resulting in functional obstruction. HSCR is attributed to a failure of migration of neural crest cells (enteric ganglion precursors) along the developing gut. RET is a key regulator of the development of the enteric nervous system (ENS) and the major HSCR-causing gene. Deleterious DNA alterations (“mutations”) in RET coding sequence (CDS) account for ≈50% of the familial and 15%-20% of the sporadic cases. Other HSCR genes identified encode protein members of interrelated signalling pathways involved in the ENS development: RET, EDNRB and SOX10 (Angrist et al, 1996; Hoffstra et al, 1999; Pingualt et al, 1998; Puffenberger et al, 1994). Mutations in genes other than RET explain ≈7% of the cases. In addition to RET mutations, RET single nucleotide polymorphisms (SNPs; “common variants”; in >1% of the population) and haplotypes are strongly associated with HSCR, with the largest contribution to risk made by an intron 1 functional SNP (rs2435357; Amiel et al, 2008) which has low penetrance, a sex-dependent effect and explains only a small fraction of the HSCR cases. It is thought that SNPs could act as modifiers of the mutations in the major HSCR genes and/or act themselves as low susceptibility loci. KEY ISSUES: (i) DNA alterations in RET (either rare or common) or other HSCR genes cannot account for the totality of the HSCR patients; and (ii) mutations in HSCR genes have reduced penetrance and phenotypic variability (i.e., length of the aganglionosis). This implies that (i) other genes are to be found; (ii) the effect of a mutation is modulated by other loci (modifiers) and (iii) that more than one gene is required for the disease manifestation. HSCR has become a model for the study of other complex disorders. The genetic complexity of HSCR can be understood in light of the molecular events that take place during the ENS development. The success of the colonization of the gut by the enteric ganglion precursors (Gariepy, 2001) depends on the synchronization and balance of the signalling networks implicated. DNA alterations in the genes encoding the implicated molecules may interfere with the colonization process, and consequently represent a primary etiology for HSCR. HSCR may therefore result from mutations in a major gene encoding a crucial molecule (whose penetrance may be modulated by other alleles) and/or from accumulation of less severe mutations in several genes. The HSCR phenotype may be a consequence of the interplay and/or accumulation of both common and rare functional and deleterious DNA variants in genes involved in ENS development, and despite the importance of RET, additional HSCR susceptibility genes exist. NEUREGULIN-1 (NRG1): NRG1 plays an important role in ENS development and maintenance and we found it to be an additional major HSCR susceptibility gene through our genome-wide association study (GWAS) on Chinese individuals (Garcia-Barcelo et al, 2009). We showed that aside from the RET SNPs, the strongest associations were found for two SNPs located in intron 1 of NRG1 on 8p12, with rs16879552 and rs7835688 yielding odds ratios of 1.68 [CI95%:(1.40,2.00), p=1.80x10-8] and 1.98 [CI95%:(1.59,2.47), p=1.12x10-9], respectively, for the heterozygous risk genotypes under an additive model. There was also a significant interaction between RET and NRG1 (p=0.0095), increasing the odds ratio 2.3-fold to 19.53 for the RET rs2435357 risk genotype (TT) in the presence of the NRG1 rs7835688 heterozygote. These NRG1 HSCR-associated SNPs are not predicted to functionally affect the gene. Thus, the most probable explanation is that the HSCR-associated NRG1 SNPs loci are in linkage disequilibrium (LD) with a functional variant. LD in the vicinity of the HSCR-associated NRG1 SNPs spans ~350Kb. Thus, we hypothesized that a common causative/functional variant must lie within this region. Several lines of evidence indicate that in addition to common variants/SNPs, rare variants may contribute substantially to the multifactorial inheritance of complex diseases. Moreover, the genes in which disease-associated common variants are found are to be considered as candidates for the search of deleterious rare variants in the coding regions (Bodmer & Bonilla, 2008). Therefore, rare NRG1 variants contributing to HSCR likely exist. Results from recent sequencing which we have undertaking indicated the presence of novel rare variants in a sample of 300 HSCR cases that we did not find in controls. Further work is underway, increasing the sample size and characterizing the variants detected. In parallel to our GWAS, our collaborators in the International Hirschsprung's Disease Consortium, of which we are members, performed a GWAS on 220 HSCR cases and parents of European descent and found their best association with SNPs in SEMA3D (Arnold et al, 2009). We, in turn, have been able to replicate in silico their association, obtaining p<.0001 in our GWAS for our most-associated SNP in this Semaphorin gene. Significantly, Semaphorin is also involved in enteric cell migration. This prompts us to apply the same successful approach we have taken with RET and NRG1 and to sequence all coding regions in SEMA3D to find novel rare variants predisposing to HSCR. RELEVANCE: The identification of Semaphorin common and rare functional variants implicated in HSCR will not only be relevant to the scientific community but also to all health professionals by facilitating risk assessment and genetic counseling. Our findings will open new fields of investigation into those mechanisms by which a discrete number of loci interact with each other to cause disease. This will provide grounds for the comprehension of other multifactorial disorders. HSCR has become a model for the study of other complex disorders. Elucidating HSCR is especially relevant in China where HSCR has one of the highest incidences (Torfs, 1998). Objective: to identify Semaphorin rare variants by re-sequencing 16 SEMA3D exons in 100 HSCR patients.


List of Research Outputs

Cherny S.S., Associate Editor (from 1997 to present), Behavior Genetics. 2010.
Cherny S.S., Associate Editor, Behavior Genetics. Springer, 2009.
Cherny S.S., Editorial Board, Genetics Research International. 2010.
Cherny S.S., Tang S.M., Sribudiani Y., Miao X., So M.T., Sham P.C., Tam P.K.H., Garcia-Barcelo M.M. and Hofstra R.M., Fine mapping of Hirschsprung's disease loci in 9q31 (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009.
Cherny S.S., Member, Advisory Board, Journal of Child Psychology & Psychiatry. 2009.
Cherny S.S., Member, Editoral Board, Genetics Research International. 2010.
Cherny S.S., Member, Editorial Advisory Board, Open Genetics Reviews. Bentham Science, 2009.
Cherny S.S., Member, Editorial Advisory Board, The Open Genomics Journal. Bentham Science, 2009.
Cheung B.M.Y., Ong K.L., Tso A.W.K., Cherny S.S., Sham P.C., Lam T.H. and Lam K.S.L., Gamma-glutamyl transaminase level predicts the development of hypertension., Presented at the Hong Kong College of Cardiology 18th Annual Scientific Congress, May 14-16, Hong Kong, 2010. 18: 33.
Cheung B.M.Y., Ong K.L., Tso A.W.K., Lam K.S.L., Cherny S.S. and Sham P.C., Using glycosylated hemoglobin to define the metabolic syndrome in United States adults., Presented at the Hong Kong College of Cardiology 18th Annual Scientific Congress, May 14-16, Hong Kong, 2010. 18: 33.
Cornes B.K., Tang S.M., Leon Y.Y., Hui K.J.W.S., So M.T., Miao X., Cherny S.S., Sham P.C., Tam P.K.H. and Garcia-Barcelo M.M., Haplotype analysis reveals a possible founder effect of RET mutation R114H for Hirschsprung's disease in the Chinese population, PLoS One. 2010, 5 (6): e10918.
Garcia-Barcelo M.M., Yeung M.Y., Miao X.P., Tang S.M., Chen G., So M.T., Ngan E.S.W., Lui V.C.H., Chen Y., Liu X., Hui K.J.W.S., Li L., Guo W.H., Sun X.B., Tou J.F., Chan K.W., Wu X.Z., Song Y., Chan D., Cheung K.M.C., Chung P.H.Y., Wong K.K.Y., Sham P.C., Cherny S.S. and Tam P.K.H., Genome-wide association study identifies a susceptibility locus for biliary atresia on 10q24.2, Human Molecular Genetics. 2010, 19 (14): 2917-2925.
Garcia-Barcelo M.M., Tang W.Y., Miao X., Tang S.M., So M.T., Leon Y.Y., Sham P.C., Cherny S.S. and Tam P.K.H., Identification of rare variants in the NRG1 gene of Hirschsprung's patients (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009.
Kung A.W.C., Xiao S., Cherny S.S., Li H.Y., Gao Y., Tso G., Lau K., Luk K.D.K., Liu J.M., Cui B., Zhang M.J., Zhang Z.L., He J.W., Yue H., Xia W.B., Luo L.M., He S.L., Kiel D.P., Karasik D., Hsu Y.H., Cupples L.A., Demissie S., Styrkarsdottir U., Halldorsson B.V., Sigurdsson G., Thorsteinsdottir U., Stefansson K., Richards B., Zhai G., Soranzo N., Valdes A., Spector T.D. and Sham P.C., Association of JAG1 with Bone Mineral Density and Osteoporotic Fractures: A Genome-wide Association Study and Follow-up Replication Studies, American Journal of Human Genetics. 2010, 86 (2): 229-239.
Kwan S.H., Cherny S.S., Kung A.W.C. and Sham P.C., Novel Sib Pair Selection Strategy Increases Power in Quantitative Association Analysis, Behavior Genetics. 2010, 39 (5): 571-579.
Ong K.L., Tso A.W.K., Cherny S.S., Sham P.C., Lam K.S.L., Jiang C.Q., Thomas G.N., Lam T.H. and Cheung B.M.Y., A genetic variant in the gene encoding fibrinogen beta chain predicted development of hypertension in Chinese men, Thrombosis and Haemostasis. 2010, 103 (4): 728-735.
Ong K.L., Tso A.W.K., Cherny S.S., Sham P.C., Lam K.S.L., Jiang C.Q., Thomas G.N., Lam T.H. and Cheung B.M.Y., A genetic variant in the gene encoding fibrinogen beta chain predicted incident hypertension in Chinese men, Annual Scientific Meeting and Annual General Meeting of Hong Kong Society of Endocrinology, Metabolism and Reproduction, Nov 2009, Hong Kong. 2009.
Ong K.L., Tso A.W.K., Cherny S.S., Sham P.C., Lam K.S.L., Jiang C.Q., Thomas G.N., Lam T.H. and Cheung B.M.Y., Adiponectin gene polymorphisms, plasma adiponectin level and persistent hypertension in Hong Kong Chinese, British Pharmacological Society Winter Meeting, Dec 2009, London, UK. 2009.
Ong K.L., Tso A.W.K., Cherny S.S., Sham P.C., Lam K.S.L., Jiang C.Q., Thomas G.N., Lam T.H. and Cheung B.M.Y., Association of a genetic polymorphism in the gene encoding fibrinogen beta chain with hypertension in Hong Kong Chinese., 15th Medical Research Conference, HKU. Hong Kong Medical Journal.. 2010, 16: 51.
Ong K.L., Tso A.W.K., Cherny S.S., Sham P.C., Lam K.S.L., Jiang C.Q., Thomas G.N., Lam T.H. and Cheung B.M.Y., Association of a genetic polymorphism in the gene encoding fibrinogen β chain with hypertension in Hong Kong Chinese, 14th Research Postgraduate Symposium, Faculty of Medicine, HKU, Dec 2009, Hong Kong. 2009.
Ong K.L., Tso A.W.K., Leung Y.H., Xu A., Cherny S.S., Sham P.C., Lam K.S.L. and Cheung B.M.Y., C-reactive protein as a predictor of hypertension in the Hong Kong cardiovascular risk prevalence study (CRISPS) cohort, Presented at the International Congress of Cardiology, Hong Kong, February 26-28, 2010.
Ong K.L., Tso A.W.K., Leung Y.H., Cherny S.S., Sham P.C., Cheung B.M.Y. and Lam K.S.L., Relationship of genetic variants gene encoding adrenomedullin with hypertension and dysglycaemia in Hong Kong Chinese, Annual Scientific Meeting of Hong Kong Society of Endocrinology. 2009.
Ong K.L., Tso A.W.K., Leung Y.H., Cherny S.S., Sham P.C., Cheung B.M.Y. and Lam K.S.L., Relationship of genetic variants in gene encoding adrenomedullin with hypertension and dysglycaemia in Hong Kong Chinese., 15th Medical Research Conference, HKU. Hong Kong Medical Journal.. 2010, 16: 50.
Ong K.L., Tso A.W.K., Leung Y.K., Cherny S.S., Sham P.C., Cheung B.M.Y. and Lam K.S.L., Relationship of genetic variants in gene encoding adrenomedullin with hypertension and dysglycaemia in Hong Kong Chinese, 13th Annual Scientific Meeting of the Institute of Cardiovascular Science and Medicine, Co-morbidity Hypertension / Diabetes: which one do we treat, Dec 2009, Hong Kong. 2009.
Ong K.L., Tso A.W.K., Cherny S.S., Sham P.C., Lam T.H., Lam K.S.L. and Cheung B.M.Y., Relationship of liver enzymes with hypertension in Hong Kong Chinese., 5th International Symposium on Healthy Aging. 2010.
Ong K.L., Tso A.W.K., Leung Y.H., Cherny S.S., Sham P.C., Cheung B.M.Y. and Lam K.S.L., Relationship of plasma interleukin-6 and its genetic variants with hypertension in Hong Kong Chinese., 15th Medical Research Conference, HKU. Hong Kong Medical Journal.. 2010, 16: 50.
Ong K.L., Tso A.W.K., Lam K.S.L., Cherny S.S., Sham P.C. and Cheung B.M.Y., Using glycosylated haemoglobin to define the metabolic syndrome in United States adults, Diabetes Care. 2010.
Ong K.L., Tso A.W.K., Lam K.S.L., Cherny S.S., Sham P.C. and Cheung B.M.Y., Using glycosylated hemoglobin to define the metabolic syndrome in United States adults., 5th International Symposium on Healthy Aging. 2010.
So H.C., Cherny S.S. and Sham P.C., Evaluating Variance in Liability Explained by Individual Genetic Variants and Relationship to Individualized Risk Prediction, Paper presented at the 18th Annual Meeting of the International Genetic Epidemiology Society, Honolulu, Hawaii, USA, October 10-20, 2009.
So H.C., Chen R.Y.L., Chen E.Y.H., Cheung E.F.C., Cherny S.S. and Li T., Genome-wide association study of schizophrenia in a Chinese population, Poster presented at the 59th Annual Meeting of the American Society of Human Genetics, Honolulu, Hawaii, USA, October 22, 2009.
So H.C., Fong P.Y., Chen R.Y.L., Hui T.C.K., Ng M.Y.M., Cherny S.S., Mak W.W., Cheung E.F.C., Chan R.C.K., Chen E.Y.H., Li T. and Sham P.C., Identification of Neuroglycan C and Interacting Partners as Potential Susceptibility Genes for Schizophrenia in a Southern Chinese Population, American Journal of Medical Genetics Part B (Neuropsychiatric Genetics). 2010, 153B (1): 103-113.
Tang S.M., Sribudiani Y., Miao X., de Vries A.R., Burzynski G., So M.T., Leon Y.Y., Yip B.H.K., Osinga J., Hui K.J.W.S., Verheij J.B.G.M., Cherny S.S., Tam P.K.H., Sham P.C., Hofstra R.M.W. and Garcia-Barcelo M.M., Fine mapping of the 9q31 Hirschsprung's disease locus, Human Genetics. 2010, 127(6): 675-683.
Tang S.M., Garcia-Barcelo M.M., Cherny S.S., Sham P.C. and Tam P.K.H., Genome-wide profile of copy number variants for Hirschsprung's disease (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009.
Yip B.H.K., Ngan E.S.W., Garcia-Barcelo M.M., Cherny S.S., Tang S.M., Sham P.C. and Tam P.K.H., Quantifying epistasis between two sets of signaling pathway genes by canonical correlation analysis: with application on Hirschsprung's disease (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009.


Researcher : Cheung C
Project Title:A single cohort prospective MRI study of symptoms and brain structure maturation in autism
Investigator(s):Cheung C, McAlonan GM, Chua SE, Sham PC
Department:Psychiatry
Source(s) of Funding:Small Project Funding
Start Date:12/2008
Abstract:
OBJECTIVES : 1) To use magnetic resonance imaging (MRI) technique to investigate how brain matures from childhood to early adulthood in a group of 25 people with autism and their matched controls. The proposed study is a follow up of children who were scanned for the first time during 2003 - 2005, between the ages of 6 to 17 years old. 2) To characterize the change in autistic symptom profile and cognitive abilities of patients across different life stages, and to associate these changes with the developmental patterns of brain anatomical structures. BACKGROUND : The challenges of autism Autism is a pervasive developmental disorder that affects the whole life of the patient. It is characterized by three domains: 1) difficulties in reciprocal social interaction; 2) impaired language & communication; and 3) repetitive behavior & stereotyped interest (Kanner, 1943). It is a global issue for human society and healthcare. The incidence of autism is thought to be rising. It is estimated that 16.1 out of 10 000 children under the age of fifteen has a diagnosis of autism spectrum disorder in Hong Kong (Wong & Hui, 2008). However, what changes in brain structure and function form the basis of autism remains unclear and consequently treatment options are limited and do not directly target core autistic symptoms(Oswald & Sonenklar, 2007). Brain imaging and autism Magnetic resonance imaging (MRI) is a safe and non-invasive procedure used widely around the world for the diagnosis and treatment of a range of illnesses and disorders. One of the challenges of imaging in autism is that this disorder encompasses a wide spectrum, and many groups studying autism adopt different methodologies (Amaral, Schumann, & Nordahl, 2008). Consequently there is lack of agreement in the literature. Further complicating the story is the differential time point that each study captures along the course of brain development. For example, we previously identified grey matter deficit in orbital-frontal, prefrontal, striatal and parietal regions in autism (mean age=12yrs) thought to be involved in information processing, social cognition and language (McAlonan et al., 2005). Over a broader age range (age 8-44), reduced orbital-frontal grey matter was also observed in children and adolescences. However, an excess in orbital-frontal grey matter was reported in adults with autism when compared to controls (Hardan et al., 2006). Interestingly, in a group of very young children with autism (age 2), grey matter excess in the frontal region is reported (Hazlett et al., 2005). Thus the developmental trajectory in autism based on evidence from cross-sectional studies appears to follow an atypical course. Similar inconsistency exists in diffusion tensor imaging (DTI) studies of white matter microstructure. Very young children with autism are postulated to have an accelerated white matter maturation compared to controls, (age 1.8-3.3)(Ben Bashat et al., 2007). However, we and others have found that older children with autism have more regions with DTI ‘deficit’ as measured by fractional anisotropy (aged 6-16; Cheung et al, under revision(Barnea-Goraly et al., 2004). Given this variation in results across different age groups, what is needed is a longitudinal study in a single cohort of patients. Symptoms of autism change over time Accompanying these brain changes, the symptom profile of autism also changes across different life stages. Although diagnosis is relatively stable after the age of 2 to 3 year-old (Charman et al., 2005; Lord et al., 2006), symptoms generally improve continuously from childhood to adolescence (McGovern & Sigman, 2005; Mesibov, Schopler, Schaffer, & Michal, 1989), and into early adulthood(Piven, Harper, Palmer, & Arndt, 1996). Impairments in the social and the communication domains improve more in childhood and adolescence, while the repetitive behaviors lessen in adulthood (Piven et al., 1996; Seltzer et al., 2003). However, how brain changes relate to these symptom improvements is not fully understood, with few if any publications covering longitudinal follow-up studies of brain maturation in autism. PURPOSE : We purpose a follow up study of a group of subjects previously recruited 3 to 5 years ago, aged 6-17 at first scan. The aim is to understand the developmental course of autism, in terms of brain structure (volume and white matter microstructure) when children migrate through adolescence and early adulthood. HYPOTHESIS : It is hypothesized that outcome measures of symptom severity (i.e. prognosis) will be closely linked to brain changes during this time period.


List of Research Outputs

Cheung C., Drug abuse and the developing brain, Lai Chack Middle School. 麗澤中學, 2009.
Cheung C., Drug abuse and the developing brain, School of Continuing and Professional Education, The Hong Kong Institute of Education. 2010.
Cheung C., Yee Y.F., Fung G.C.M., Yu K.K.K., Yao N., You Y., McAlonan G.M. and Chua S.E., MRI brain scan study of minor physical anomalies to aid the early diagnosis of autism, International College of Neuropsychopharmacology 2010, Hong Kong (June 6-10, 2010). 2010.
Cheung C., Special Contributions Award, Centre of Education, The Mental Health Association of Hong Kong. 2010.
Cheung C., Understanding Autism, Cornwall Special School. 2010.
Cheung V., Chiu C.P.Y., Law C.W., Cheung C., Hui C.L.M., Chan K.K.S., Sham P.C., Deng Y., Tai K.S., Khong P.L., McAlonan G.M., Chua S.E. and Chen E.Y.H., Positive symptoms and white matter microstructure in never-medicated first episode schizophrenia, Psychological Medicine. 2010, 40: 1-12.
Deng Y., McAlonan G.M., Cheung C., Chiu C.P.Y., Law C.W., Cheung V., Sham P.C., Chen E.Y.H. and Chua S.E., A naturalistic study of grey matter volume increase after early treatment in anti-psychotic naïve, newly diagnosed schizophrenia, Psychopharmacology. 2009, 206: 437-446.
Fung G.C.M., Fung Y.Y., Cheung C., You Y., McAlonan G.M. and Chua S.E., MRI measurement of intracranial MPAs (minor physical anomalies) in autism, International Meeting of Autism Research 2010, Philadephia, USA. (May 20-22, 2010). 2010.
Leung M.K., Cheung C., Yu K.K.K., Yip B.H.K., Sham P.C., Li Q., Chua S.E. and McAlonan G.M., Gray Matter in First-Episode Schizophrenia Before and After Antipsychotic Drug Treatment. Anatomical Likelihood Estimation Meta-analyses With Sample Size Weighting, Schizophrenia Bulletin . 2009, 16.
Li Q., Cheung C., Wei R., Wong P., McAlonan G.M. and Wu E., Oral presentation: Prenatal immune challenge as a risk factor for white matter microstructural anomalies relevant to schizophrenia, The 15th Biennial Winter Workshop in Psychoses 2009, Barcelona, Espana (November 15-18, 2009). 2010.
Li Q., Cheung C., Hui E.S., Feldon J., Meyer U., Chung S.K., Chua S.E., Sham P.C., Wu E.X. and McAlonan G.M., Prenatal Immune Challenge Is an Environmental Risk Factor for Brain and Behavior Change Relevant to Schizophrenia: Evidence from MRI in a Mouse model, PLOSone. 2009, e6354.
Li Q., Cheung C., Cheung V., Zhang X., Wei R., Wong P., You Y.Q., Hui E., Chua S.E., McAlonan G.M. and Wu E.X., The timing of prenatal immune challenge determines the extent of postnatal white matter microstructural anomalies in a mouse model of schizophrenia, The International Journal of Neuropsychopharmacol. 2010.
Li Q., Cheung C., Wei R., Cheung V., Hui E.S., You Y., Wong P., Chua S.E., McAlonan G.M. and Wu E.X., Voxel-based analysis of postnatal white matter microstructure in mice exposed to immune challenge in early or late pregnancy, Neurolmage. 2010, 52(1): 1-8.
McAlonan G.M., Li Q., Cheung C., Wei R., Chua S.E., Sham P.C. and Wu E.X., Evidence that prenatal infection is a risk factor for brain and behaviour changes relevant to schizophrenia and autism, 41st European Brain and Behaviour Society Meeting (EBBS), Rhodes 2009. (September 13-18, 2009). 2010.
McAlonan G.M., Li Q., Cheung C., Wei R., Cheung V., Hui E.S.K., Wong P., Chua S.E. and Wu E.X., Oral presentation: The Timing of Prenatal Immune Challenge Determines the Extent of White Matter Microstructural Anomalies Relevant to Autism, International Meeting for Autism Research (IMFAR) Chicago 2010. (May 19-25, 2010). 2010.
McAlonan G.M., Li Q. and Cheung C., The timing and specificity of prenatal immune risk factors for autism modeled in the mouse (review), Neurosignals. 2010, (in press).
McAlonan G.M., Cheung C., Li Q., Cheung V., Hui E.S.K., Wei R., Wong P., Chua S.E. and Wu E.X., The timing of prenatal immune challenge determines the extent of white matter microstructural anomalies relevant to schizophrenia, The 2nd Biennial Schizophrenia International Research Society Conference (SIRS), Florence, Italy, 2010. (April 9-16, 2010). 2010.


Researcher : Cheung V
Project Title:Longitudinal follow-up of patients with first-episode psychosis: a DTI study
Investigator(s):Cheung V, McAlonan GM, Chua SE, Sham PC
Department:Psychiatry
Source(s) of Funding:Small Project Funding
Start Date:02/2009
Completion Date:08/2009
Abstract:
OBJECTIVES : To investigate the change in white matter microstructure in schizophrenia in the years following a first episode of psychosis. This is a three to four year follow-up DTI-MRI study of first-episode patients with psychosis, scanned when drug-naive at their first presentation in 2004 – 2006 and 3 weeks after drug treatment. The aim is to establish what markers at time = 0 and time = 3 weeks can predict brain structural change and outcome at time = 3-4 years. BACKGROUND : Schizophrenia is a serious heritable mental disorder, affecting 1% people worldwide. It usually presents in young adults with psychosis i.e. hallucinations or delusions. Anti-psychotic drugs classically block dopamine receptors in the basal ganglia (striatum) in the brain and take effect after 3 weeks (Johnstone et al 1978). We have previously shown that grey matter volume (Chua et al., 2007) and white matter microstructure (Cheung et al 2007) is abnormal at first presentation prior to drug treatment. Three weeks after drug treatment white matter indices continue to deviate from controls (Cheung et al in preparation). Brain structural abnormalities appear to be progressive. For example, global grey matter loss is evident at 1-year follow-up (Cahn et al., 2002) and 2-year follow-up (Farrow et al., 2005). However, it is unknown how white matter microstructure is affected by continued drug treatment and illness chronicity. It is also not known whether white matter microstructure prior to treatment or immediately following treatment, can predict progression of the disease. Diffusion tensor imaging is a fairly new medical research tool that quantifies the diffusion extent and direction of water molecules inside living tissues such as nerves (Basser, Pajevic et al., 2000). In human brain, water molecules tend to diffuse along the direction of the axonal fibres wrapped by myelin sheath. Therefore, the direction of water diffusion inside the brain can reveal the orientation and structure of white matter comprised of millions of axonal fibers grouped together in myelinated sheaths (Basser, 1995). Quantification of water diffusion across brain tissues by fractional anisotropy (FA) is a conventional measure of directional diffusion with values ranging from 0, completely isotropic to 1, unidirectional (Basser, 1995). Along white matter tracts, horizontal diffusion is restricted and water molecules tend to diffuse in the direction of the tract, hence FA values are higher than in grey matter or CSF. The reduction in FA found in patients with schizophrenia compared to controls, reflects white matter tract abnormalities, such as dislocation, disruption or disorganization (Konrad & Winterer, 2007). Thus, FA is a useful proxy measure of ‘connectivity’ between different brain regions (Davis et al., 2003). The evidence from DTI studies of schizophrenia to date is consistent with dysconnectivity of the brain in schizophrenia particularly in fronto-striatal-temporal circuits. Reduced FA within prefrontal and temporal lobes (Ardekani et al 2003, Rametti et al 2007, Szeszko et al 2005 , and in the white matter tracts that connect these regions: uncinate fasciculus, cingulum bundle (Sun et al., 2003; Hubl et al., 2004, Kubicki et al., 2003, 2005, Zetzsche et al., 2007), arcuate fasciculus (Hubl et al., 2004, Kubicki et al., 2005), inferior longitudinal fasciulus (Ashtori et al., 2007) are most commonly found when comparing patients with healthy controls (for a review see Kanaan et al., 2005; Kubicki et al., 2007). FA in the largest white matter inter-hemispheric tract, the corpus callosum, has also been found to be lower in schizophrenia (Foong et al., 2000, Foong et al., 2002, Ardekani et al., 2003, Hubl et al., 2004, Kalus et al., 2005) as have values in the striatum (Hubl et al 2004, Kubicki et al 2005, Szeszko et al 2005), and hippocampal / parahippocampal region (Ardekani et al 2003, Kalus et al 2004 and 2005). Chronicity and neuroleptic treatment are known to affect interpretation of brain structural differences. Thus, in recent years, the research focus in brain imaging has turned to newly-ill and neuroleptic-naïve patients. In the first comprehensive voxel-based DTI study of never-medicated patients with first episode of schizophrenia, we reported significantly decreased FA values of the patient relative to healthy controls, in the right posterior limb of internal capsule, left middle temporal gyrus, right substantia nigra, left cerebral peduncle, and splenium of corpus callosum (Cheung et al., 2007). PURPOSE : We propose to follow-up white matter pathology using DTI brain scanning in a cohort of first-episode patients with schizophrenia, who were first scanned prior to antipsychotic medication and 3 weeks after. This re-scan will occur 3 to 4 years post-treatment


List of Research Outputs

Cheung C., Chua S.E., Cheung V., Khong P.L., Tai K.S., Wong T.K.W., Ho T.P. and McAlonan G.M., White matter fractional anisotrophy differences and correlates of diagnostic symptoms in autism, Journal of Child Psychology and Psychiatry. 2009, 50: 1102-1112.
Cheung V., Chiu C.P.Y., Law C.W., Cheung C., Hui C.L.M., Chan K.K.S., Sham P.C., Deng Y., Tai K.S., Khong P.L., McAlonan G.M., Chua S.E. and Chen E.Y.H., Positive symptoms and white matter microstructure in never-medicated first episode schizophrenia, Psychological Medicine. 2010, 40: 1-12.
Deng Y., McAlonan G.M., Cheung C., Chiu C.P.Y., Law C.W., Cheung V., Sham P.C., Chen E.Y.H. and Chua S.E., A naturalistic study of grey matter volume increase after early treatment in anti-psychotic naïve, newly diagnosed schizophrenia, Psychopharmacology. 2009, 206: 437-446.
Li Q., Cheung C., Cheung V., Zhang X., Wei R., Wong P., You Y.Q., Hui E., Chua S.E., McAlonan G.M. and Wu E.X., The timing of prenatal immune challenge determines the extent of postnatal white matter microstructural anomalies in a mouse model of schizophrenia, The International Journal of Neuropsychopharmacol. 2010.
Li Q., Cheung C., Wei R., Cheung V., Hui E.S., You Y., Wong P., Chua S.E., McAlonan G.M. and Wu E.X., Voxel-based analysis of postnatal white matter microstructure in mice exposed to immune challenge in early or late pregnancy, Neurolmage. 2010, 52(1): 1-8.
McAlonan G.M., Li Q., Cheung C., Wei R., Cheung V., Hui E.S.K., Wong P., Chua S.E. and Wu E.X., Oral presentation: The Timing of Prenatal Immune Challenge Determines the Extent of White Matter Microstructural Anomalies Relevant to Autism, International Meeting for Autism Research (IMFAR) Chicago 2010. (May 19-25, 2010). 2010.
McAlonan G.M., Cheung C., Li Q., Cheung V., Hui E.S.K., Wei R., Wong P., Chua S.E. and Wu E.X., The timing of prenatal immune challenge determines the extent of white matter microstructural anomalies relevant to schizophrenia, The 2nd Biennial Schizophrenia International Research Society Conference (SIRS), Florence, Italy, 2010. (April 9-16, 2010). 2010.


Researcher : Chiu CPY
Project Title:Paternal age effect on the outcome of first episode psychosis
Investigator(s):Chiu CPY, Chen EYH, Lam MLM, Chan KW, Hui CLM
Department:Psychiatry
Source(s) of Funding:Seed Funding Programme for Basic Research
Start Date:06/2009
Abstract:
The aetiology of schizophrenia is a product of multiple contributing factors, and amongst these aetiological factors many have been found to have a potential effect on the outcome of schizophrenia. Studying prognostic implications of aetiological factors not only informs clinical management, but also suggests ways to begin to consider potential subgroups of the disorder based on aetiological factors. Obstetric complications (OCs), familial schizophrenia, age of onset, duration of untreated psychosis (DUP), social class and birth rank have been extensively studied and found to be of prognostic implication in some reports. Advanced paternal age has been reported both as a risk factor in disease development and as a predisposing factor for certain sub-types of general medical illnesses (Montgomery, Lambe, Olsson, & Ekbom, 2004; Vestergaard, Mork, Madsen, & Olsen, 2005; Fletcher & Foley, 1993). In schizophrenia, early studies observed that patients with schizophrenia have an older mean paternal age when compared to other psychiatric diagnoses or the normal population. Since then, advanced paternal age has been identified as a risk factor for schizophrenia in several birth cohorts (Brown et al., 2002; Malaspina, 2001) and army cohorts. The effect was echoed by findings from several case control studies and demonstrated to be dose-related in an Israeli birth cohort (Malaspina et al., 2001). In addition, advanced paternal age is particularly associated with sporadic rather than familial schizophrenia (Malaspina, 2001; Sipos et al., 2004). Whether or not the paternal age effect extends to the clinical outcome of schizophrenia was previously explored in a sample of young people suffering from early psychosis from the Early Assessment Service for Young People (EASY). 191 subjects who were suffering from a first episode of psychosis and fulfilling the ICD-10 diagnosis of schizophrenia at the end of first year were recruited. A paternal age effect in terms of psychotic relapses within the first year was found for subjects whose fathers were 40 years or older at the time of their births, when compared to those whose fathers were 29 or below (χ2 = 9.5, df = 1, p = 0.003), or 30 – 39 years(χ2 = 9.4, df = 1, p = 0.003). This effect was not due to other potential factors such as maternal age, age of onset or paternal occupation. How advanced paternal age may take effect in older adults (26-55 years) with first episode psychosis was not previously investigated. In this study, we would like to extend our observation to first-episode schizophrenia patients in the older age range. Our hypothesis is that patients in this older age range (26-55 years) with older fathers have a poorer outcome in terms of the number of relapses, and level of occupational functioning. We also speculated any identified effect of paternal age to be unrelated to other potential aetiological factor such as obstetric complications, birth rank, family history; and that the main hypothesis would still stand even when potential confounding factors were taken into consideration.


List of Research Outputs

Chan K.K.S., Hui C.L.M., Chiu C.P.Y., Lam M.L.M., Chan K.W., Lin J., Xu J., Tang Y.M., Wong G.H.Y., Longenecker J.M. and Chen E.Y.H., A 3-year prospective study of spontaneous eye-blink rate in first-episode schizophrenia: Relationships with neurocognitive functions and relapse, 2nd Schizophrenia International Research Society Conference (April 10-14, 2010), Florence, Italy. 2010.
Chan K.K.S., Wong G.H.Y., Hui C.L.M., Tang Y.M., Chan K.W., Lam M.L.M., Chiu C.P.Y. and Chen E.Y.H., Game Theoretical Approach to Theory of Mind Deficits in Schizophrenic Patients with Delusion(s) of Reference, Schizophrenia Research. 2010, 117 (2-3): 286.
Chan K.W., Chiu C.P.Y., Lam M.L.M., Hui C.L.M., Wong G.H.Y., Tang Y.M., Chan K.K.S. and Chen E.Y.H., Relationship of neurocognitive function and impairment of insight in first episode schizophrenia, Schizophrenia Research. 2010, 117 (2-3): 209.
Chang W.C., Tang Y.M., Chiu C.P.Y., Hui C.L.M., Lam M.L.M., Wong G.H.Y., Law C.W., Tso S., Chan K., Hung S.F., Chung D.W.S. and Chen E.Y.H., Gender differences in patients presented with first-episode psychosis in Hong Kong, Schizophrenia Research. 2010, 117 (2-3): 281-2.
Chen E.Y.H., Hui C.L.M., Lam M.L.M., Chiu C.P.Y., Law C.W., Chung D.W.S., Tso S., Pang E.P.F., Chan K.T., Wong Y.C., Mo F.Y.M., Chan K.P.M., Yao T.J., Hung S.F. and Honer W.G., Maintenance treatment with quetiapine versus discontinuation after one year of treatment in patients with remitted first episode psychosis: randomised controlled trial, British Medical Journal. 2010, 341: c4024.
Cheung V., Chiu C.P.Y., Law C.W., Cheung C., Hui C.L.M., Chan K.K.S., Sham P.C., Deng Y., Tai K.S., Khong P.L., McAlonan G.M., Chua S.E. and Chen E.Y.H., Positive symptoms and white matter microstructure in never-medicated first episode schizophrenia, Psychological Medicine. 2010, 40: 1-12.
Deng Y., McAlonan G.M., Cheung C., Chiu C.P.Y., Law C.W., Cheung V., Sham P.C., Chen E.Y.H. and Chua S.E., A naturalistic study of grey matter volume increase after early treatment in anti-psychotic naïve, newly diagnosed schizophrenia, Psychopharmacology. 2009, 206: 437-446.
Lam M.L.M., Pearson V., Ng R.M.K., Chiu C.P.Y., Law C.W. and Chen E.Y.H., What does recovery from psychosis mena? Perceptions of young first-episode patients, International Journal of Social Psychiatry. 2010, 2-9.
Tang Y.M., Chiu C.P.Y., Hui C.L.M., Chan K.K.S., Lam M.L.M., Chan K.W., Wong G.H.Y. and Chen E.Y.H., Clinical and cognitive correlates of perceived extent of recovery in Chinese patients with psychosis, Schizophrenia Research. 2010, 117 (2-3): 516.
Tang Y.M., Wong G.H.Y., Hui C.L.M., Lam M.L.M., Chiu C.P.Y., Chan K.W., Chung D.W.S., Tso S., Chan K.P.M., Yip K.C., Hung S.F. and Chen E.Y.H., Early intervention for psychosis in Hong Kong - the EASY programme, Early Intervention in Psychiatry. 2010, 4 (3): 214-219.
Tang Y.M., Lam M.L.M., Wong H.Y., Hui C.L.M., Chiu C.P.Y., Law C.W., Chung D.W.S., Tso S., Yip K.C., Chen E.Y.H. and Hung S.F., Time to a stop or a change in prescription of initial antipsychotic medication in first-episode schizophrenic patients: A naturalistic study, 2nd Schizophrenia International Research Society Conference (April 10-14, 2010), Florence, Italy. 2010.
Wong G.H.Y., Tao H.J., He Z., Liu H.H., Chiu C.P.Y., Chan K.W., Lam M.L.M., Hui C.L.M., Tang Y.M., Wang Y.H., Xue Z.M., Liu Z.N. and Chen E.Y.H., Delusions of reference, excessive top-down processing, and default mode network in first-episode schizophrenia, Schizophrenia Research. 2010, 117 (2-3): 491.


Researcher : Chua SE
Project Title:A study of the psychological effects of the H1N1 pandemic in Hong
Investigator(s):Chua SE, Lee AM, McAlonan GM
Department:Psychiatry
Source(s) of Funding:Seed Funding Programme for Basic Research
Start Date:01/2010
Abstract:
KYE ISSUES AND PROBLEMS TO BE ADDRESSED As of 1 November 2009, the H1N1 swine influenza pandemic has affected more than 199 countries worldwide. There have been 31789 confirmed cases in Hong Kong and 39 deaths as of 9th November, 2009 (accessed 10 Nov 2009, Surveillance and Epidemiology Branch, Centre for Health Protection, the Government of the HKSAR). The World Health Organisation announced in their weekly pandemic report (released 6 Nov 2009, update 73) that the cumulative total number of confirmed cases worldwide was over 482300 as of 1st November, 2009 and at least 6071 people died. It is noteworthy that the number of cases reported by the Centre for Health Protection in Hong Kong and The World Health Organisation is, in all likelihood, an underestimate of the real number of cases. This is because countries are now no longer required to test and report individual cases and in the situation of Hong Kong, public hospitals do not offer test to every patient with flu symptoms but only to those who are at higher risk, like young children and elderly. Originally a zoonotic virus, the H1N1 virus has recently reassorted to affect humans, and is still a relatively unknown entity. Although its spread has appeared similar to that of seasonal influenza, there are important demographic distinctions in swine influenza: healthy adults may show sudden marked deterioration, pregnant females are particularly vulnerable, children up to the age of 5 may be more at risk. It is important to examine the levels of stress, anxiety, depression as these can collectively impact on physical health and immunity of the population. Our team has previously worked on the psychological impact of SARS (severe acute respiratory syndrome) during the acute and sustained phases in Hong Kong (Chua et al 2004, McAlonan et al 2005, Lee et al 2007) and comprises health-care professionals from Family Medicine, Public Health and Psychiatry. We plan to evaluate psychological health indices and stress-inducing factors, using validated psychological instruments available bilingually for self-rating. This includes socio-demographics, the Perceived stress scale (PSS*; Cohen & Williamson 1988), the Depression Anxiety Stress Scales* (DASS; Lovibond and Lovibond 1995), the Impact of Events Scale* (IES; Weiss & Marmar 1997), and the General Health Questionnaire* (GHQ; Goldberg & Williams 1988). The main purpose of the proposed study is to provide a comprehensive “snap-shot” of the psychological effects of the H1N1 pandemic on the health of people in Hong Kong. A second purpose is to compare these indices with historical data collected during the SARS pandemic in 2003 and over the follow-up period in 2004. This study will be conducted using the above instruments in primary and specialist clinics in Hong Kong Island West and in the community. OBJECTIVES The aims of this study are: (i) Identify how the H1N1 pandemic affects the psychological health of patients and the general population in the community; (ii) Determine risk factors for health deterioration; and (iii) Propose strategies to alleviate health indices and to enhance services. HYPOTHESES We hypothesize that psychological health indices will be impacted by the H1N1 pandemic in the following ways: - Stress and emotional distress levels are higher in HCWs than healthy controls, with primary care HCWs’ psychological health being worse than that of psychiatry HCWs - Stress and emotional distress levels are higher in primary care patients than psychiatry patients. If diagnosed with H1N1, then stress and emotional distress levels higher than for non-H1N1 patients - Stress and emotional distress levels are higher in carers than in healthy controls - For all of the above, stress and emotional distress levels are higher in SARS sample than in H1N1 sample


Project Title:MRI brain scan to predict 1 year outcome in newly-diagnosed schizophrenia.
Investigator(s):Chua SE, McAlonan GM, Tai KS
Department:Psychiatry
Source(s) of Funding:General Research Fund (GRF)
Start Date:01/2010
Abstract:
1) Individuals newly diagnosed with schizophrenia will include those newly diagnosed with psychosis. This is as written in the GRF update, the rationale being that psychosis is the core feature of schizophrenia but also features in mood disorders, substance abuse, movement disorders ie it is generic to several brain disorders; 2) To follow-up the individuals for 1 year to evaluate their outcome based on structured instruments to rate symptoms and functioning; 3) To determine which individuals have "good" or "bad" outcome after 1 year; 4) To compare brain scans of "good" and "bad" patient outcome groups; 5) To generate brain regional structural predictors of "good" and "bad" group outcome; 6) To use the above to develop a reference tool on which to compare individual brain scans at first presentation to help predict future outcome and plan treatment.


List of Research Outputs

Cheung C., Yee Y.F., Fung G.C.M., Yu K.K.K., Yao N., You Y., McAlonan G.M. and Chua S.E., MRI brain scan study of minor physical anomalies to aid the early diagnosis of autism, International College of Neuropsychopharmacology 2010, Hong Kong (June 6-10, 2010). 2010.
Cheung C., Chua S.E., Cheung V., Khong P.L., Tai K.S., Wong T.K.W., Ho T.P. and McAlonan G.M., White matter fractional anisotrophy differences and correlates of diagnostic symptoms in autism, Journal of Child Psychology and Psychiatry. 2009, 50: 1102-1112.
Cheung V., Chiu C.P.Y., Law C.W., Cheung C., Hui C.L.M., Chan K.K.S., Sham P.C., Deng Y., Tai K.S., Khong P.L., McAlonan G.M., Chua S.E. and Chen E.Y.H., Positive symptoms and white matter microstructure in never-medicated first episode schizophrenia, Psychological Medicine. 2010, 40: 1-12.
Chua S.E., MRI and 1 year outcome in schizophrenia., First Maudsley SE Asia Symposium. Hong Kong, Dec 2009.. 2009.
Deng Y., McAlonan G.M., Cheung C., Chiu C.P.Y., Law C.W., Cheung V., Sham P.C., Chen E.Y.H. and Chua S.E., A naturalistic study of grey matter volume increase after early treatment in anti-psychotic naïve, newly diagnosed schizophrenia, Psychopharmacology. 2009, 206: 437-446.
Deng Y., Meyer U., Lam S.S.Y., Feldon J., Li Q., Wei R., Luk L., Chua S.E., Sham P.C., Wang Y. and McAlonan G.M., Prenatal immune challenge causes frontal-subcortical proteome changes relevant to schizophrenia and autism, The International Journal of Neuropsychopharmacol. 2010.
Fung G.C.M., Catani M., Chua S.E., Murphy D.G.M. and McAlonan G.M., Cerebellar Feedback Projections in Autism Spectrum Disorder, 14th Research Postgraduate Symposium (December 2-3, 2009). 2010.
Fung G.C.M., Fung Y.Y., Cheung C., You Y., McAlonan G.M. and Chua S.E., MRI measurement of intracranial MPAs (minor physical anomalies) in autism, International Meeting of Autism Research 2010, Philadephia, USA. (May 20-22, 2010). 2010.
Leung M.K., Cheung C., Yu K.K.K., Yip B.H.K., Sham P.C., Li Q., Chua S.E. and McAlonan G.M., Gray Matter in First-Episode Schizophrenia Before and After Antipsychotic Drug Treatment. Anatomical Likelihood Estimation Meta-analyses With Sample Size Weighting, Schizophrenia Bulletin . 2009, 16.
Li Q., Cheung C., Hui E.S., Feldon J., Meyer U., Chung S.K., Chua S.E., Sham P.C., Wu E.X. and McAlonan G.M., Prenatal Immune Challenge Is an Environmental Risk Factor for Brain and Behavior Change Relevant to Schizophrenia: Evidence from MRI in a Mouse model, PLOSone. 2009, e6354.
Li Q., Cheung C., Cheung V., Zhang X., Wei R., Wong P., You Y.Q., Hui E., Chua S.E., McAlonan G.M. and Wu E.X., The timing of prenatal immune challenge determines the extent of postnatal white matter microstructural anomalies in a mouse model of schizophrenia, The International Journal of Neuropsychopharmacol. 2010.
Li Q., Cheung C., Wei R., Cheung V., Hui E.S., You Y., Wong P., Chua S.E., McAlonan G.M. and Wu E.X., Voxel-based analysis of postnatal white matter microstructure in mice exposed to immune challenge in early or late pregnancy, Neurolmage. 2010, 52(1): 1-8.
McAlonan G.M., Li Q., Cheung C., Wei R., Chua S.E., Sham P.C. and Wu E.X., Evidence that prenatal infection is a risk factor for brain and behaviour changes relevant to schizophrenia and autism, 41st European Brain and Behaviour Society Meeting (EBBS), Rhodes 2009. (September 13-18, 2009). 2010.
McAlonan G.M., Li Q., Cheung C., Wei R., Cheung V., Hui E.S.K., Wong P., Chua S.E. and Wu E.X., Oral presentation: The Timing of Prenatal Immune Challenge Determines the Extent of White Matter Microstructural Anomalies Relevant to Autism, International Meeting for Autism Research (IMFAR) Chicago 2010. (May 19-25, 2010). 2010.
McAlonan G.M., Cheung C., Li Q., Cheung V., Hui E.S.K., Wei R., Wong P., Chua S.E. and Wu E.X., The timing of prenatal immune challenge determines the extent of white matter microstructural anomalies relevant to schizophrenia, The 2nd Biennial Schizophrenia International Research Society Conference (SIRS), Florence, Italy, 2010. (April 9-16, 2010). 2010.
Wei R., Li Q., Chua S.E. and McAlonan G.M., Prenatal exposure to valproic acid induces a dose dependent impairment in sensorimotor gating in a mouse model of autism, The International Journal of Neuropsychopharmacol. 2010.


Researcher : Chung KF
Project Title:Seizure threshold of unilateral electroconvulsive therapy
Investigator(s):Chung KF, Wong SJ
Department:Psychiatry
Source(s) of Funding:Other Funding Scheme
Start Date:07/2001
Abstract:
To find out the seizure threshold of electroconvulsive therapy and its predictors in Chinese.


Project Title:Influence of a psychiatric clerkship on medical students' attitudes toward psychiatry and mental patients
Investigator(s):Chung KF
Department:Psychiatry
Source(s) of Funding:Other Funding Scheme
Start Date:01/2002
Abstract:
To compare the effect of a standard clerkship with one augmented with a 1-hour stigma-changing programme on students' attitudes toward mental illness.


Project Title:Response to moderately suprathreshold unilateral (UL) electroconvulsive therapy (ECT): an examination of possible predictors
Investigator(s):Chung KF, Irwin MG
Department:Psychiatry
Source(s) of Funding:Other Funding Scheme
Start Date:06/2002
Abstract:
To examine factors that associate with response to moderately suprathereshold unilateral ECT.


List of Research Outputs

Chan C.Y., Lee A.M., Lam S.K., Leung K.Y., Chung K.F., Koh Y.W. and Tang C.S.K., Psychological abuse experiences are independently associated with disordered eating symptoms among pregnant women, Paper presented at the Hong Kong Psychological Society Annual Conference 2010 "Development challenges across Life Stages", Hong Kong, June 12, 2010.
Chung K.F., Psychiatric comorbidities of bipolar disorder, Hong Kong Society for Advancement of Bipolar Affective Disorder Workshop on Bipolar Disorder 2009 (August 28-29, 2009). 2009.
Chung K.F., Recent advances in bipolar disorder, Hong Kong College of Family Physicians - Lectures in psychiatric disorders, 2009 (August 16, 2009). 2009.
Chung K.F., Role of ECT in contemporary psychiatric practice, ECT Training Day 2009 organized by the Tutor Committee (Psychiatry), HA and the Hong Kong College of Psychiatrists, Hong Kong, September 2009. 2009.
Chung K.F., Tso K.C. and Chung R.T.Y., Validation of the Mood Disorder Questionnaire in the general population in Hong Kong, Comprehensive Psychiatry. 2009, 50 (5): 471-476.
Koh Y.W., Lee A.M., Leung K.Y., Chan C.Y., Tang C.S.K. and Chung K.F., Identifying Psychosocial Risk Factors for Mental Health and Psychosomatic Problems Among Expectant Fathers During Transition to Fatherhood, Paper presented at the American Psychological Science Annual Convention, Boston, May 27-30, 2010.
Yeung W.F., Chung K.F. and Zhang S.P., A randomized controlled trial of electroacupuncture for residual insomnia associated with major depressive disorder, T.W.G.H.S. Eddie Wang Chinese Medicine Postgraduate Forum, Hong Kong: Tung Wah Group of Hospitals and Hospital Authority, 2010.
Yeung W.F., Chung K.F. and Zhang S.P., Acupuncture for residual insomnia Associated with Major Depressive Disorder: A Randomized Placebo-Controlled Trial, 2009 Hong Kong - Macau Postgraduate Symposium on Chinese Medicine. Hong Kong: Modernized Chinese Medicine International Association, August 13, 2009.
Yeung W.F., Chung K.F., Zhang S.P., Yap T.G. and Law A.C.K., Electroacupuncture for Primary Insomnia: A Randomized Controlled Trial, Sleep. 2009, 32 (8): 1039-1047.
Yeung W.F., Chung K.F. and Wong C.Y., Relationship between insomnia and headache in community-based middle-aged Hong kong Chinese women, J Headache Pain. 2010, 11: 187-195.


Researcher : Deng Y
List of Research Outputs

Cheung V., Chiu C.P.Y., Law C.W., Cheung C., Hui C.L.M., Chan K.K.S., Sham P.C., Deng Y., Tai K.S., Khong P.L., McAlonan G.M., Chua S.E. and Chen E.Y.H., Positive symptoms and white matter microstructure in never-medicated first episode schizophrenia, Psychological Medicine. 2010, 40: 1-12.
Deng Y., McAlonan G.M., Cheung C., Chiu C.P.Y., Law C.W., Cheung V., Sham P.C., Chen E.Y.H. and Chua S.E., A naturalistic study of grey matter volume increase after early treatment in anti-psychotic naïve, newly diagnosed schizophrenia, Psychopharmacology. 2009, 206: 437-446.
Deng Y., Meyer U., Lam S.S.Y., Feldon J., Li Q., Wei R., Luk L., Chua S.E., Sham P.C., Wang Y. and McAlonan G.M., Prenatal immune challenge causes frontal-subcortical proteome changes relevant to schizophrenia and autism, The International Journal of Neuropsychopharmacol. 2010.


Researcher : Deng Y
List of Research Outputs

Cheung V., Chiu C.P.Y., Law C.W., Cheung C., Hui C.L.M., Chan K.K.S., Sham P.C., Deng Y., Tai K.S., Khong P.L., McAlonan G.M., Chua S.E. and Chen E.Y.H., Positive symptoms and white matter microstructure in never-medicated first episode schizophrenia, Psychological Medicine. 2010, 40: 1-12.
Deng Y., McAlonan G.M., Cheung C., Chiu C.P.Y., Law C.W., Cheung V., Sham P.C., Chen E.Y.H. and Chua S.E., A naturalistic study of grey matter volume increase after early treatment in anti-psychotic naïve, newly diagnosed schizophrenia, Psychopharmacology. 2009, 206: 437-446.
Deng Y., Meyer U., Lam S.S.Y., Feldon J., Li Q., Wei R., Luk L., Chua S.E., Sham P.C., Wang Y. and McAlonan G.M., Prenatal immune challenge causes frontal-subcortical proteome changes relevant to schizophrenia and autism, The International Journal of Neuropsychopharmacol. 2010.


Researcher : Fung GCM
List of Research Outputs

Cheung C., Yee Y.F., Fung G.C.M., Yu K.K.K., Yao N., You Y., McAlonan G.M. and Chua S.E., MRI brain scan study of minor physical anomalies to aid the early diagnosis of autism, International College of Neuropsychopharmacology 2010, Hong Kong (June 6-10, 2010). 2010.
Fung G.C.M., Catani M., Chua S.E., Murphy D.G.M. and McAlonan G.M., Cerebellar Feedback Projections in Autism Spectrum Disorder, 14th Research Postgraduate Symposium (December 2-3, 2009). 2010.
Fung G.C.M., Fung Y.Y., Cheung C., You Y., McAlonan G.M. and Chua S.E., MRI measurement of intracranial MPAs (minor physical anomalies) in autism, International Meeting of Autism Research 2010, Philadephia, USA. (May 20-22, 2010). 2010.


Researcher : Ho TP
List of Research Outputs

Cheung C., Chua S.E., Cheung V., Khong P.L., Tai K.S., Wong T.K.W., Ho T.P. and McAlonan G.M., White matter fractional anisotrophy differences and correlates of diagnostic symptoms in autism, Journal of Child Psychology and Psychiatry. 2009, 50: 1102-1112.


Researcher : Hui CLM
Project Title:2nd World Congress of Asian Psychiatry Renaming psychosis in Hong Kong
Investigator(s):Hui CLM
Department:Psychiatry
Source(s) of Funding:URC/CRCG - Conference Grants for Teaching Staff
Start Date:11/2009
Completion Date:11/2009
Abstract:
N/A


List of Research Outputs

Chan K.K.S., Hui C.L.M., Chiu C.P.Y., Lam M.L.M., Chan K.W., Lin J., Xu J., Tang Y.M., Wong G.H.Y., Longenecker J.M. and Chen E.Y.H., A 3-year prospective study of spontaneous eye-blink rate in first-episode schizophrenia: Relationships with neurocognitive functions and relapse, 2nd Schizophrenia International Research Society Conference (April 10-14, 2010), Florence, Italy. 2010.
Chan K.K.S., Wong G.H.Y., Hui C.L.M., Tang Y.M., Chan K.W., Lam M.L.M., Chiu C.P.Y. and Chen E.Y.H., Game Theoretical Approach to Theory of Mind Deficits in Schizophrenic Patients with Delusion(s) of Reference, Schizophrenia Research. 2010, 117 (2-3): 286.
Chan K.W., Chiu C.P.Y., Lam M.L.M., Hui C.L.M., Wong G.H.Y., Tang Y.M., Chan K.K.S. and Chen E.Y.H., Relationship of neurocognitive function and impairment of insight in first episode schizophrenia, Schizophrenia Research. 2010, 117 (2-3): 209.
Chang W.C., Tang Y.M., Chiu C.P.Y., Hui C.L.M., Lam M.L.M., Wong G.H.Y., Law C.W., Tso S., Chan K., Hung S.F., Chung D.W.S. and Chen E.Y.H., Gender differences in patients presented with first-episode psychosis in Hong Kong, Schizophrenia Research. 2010, 117 (2-3): 281-2.
Chen E.Y.H., Hui C.L.M., Lam M.L.M., Chiu C.P.Y., Law C.W., Chung D.W.S., Tso S., Pang E.P.F., Chan K.T., Wong Y.C., Mo F.Y.M., Chan K.P.M., Yao T.J., Hung S.F. and Honer W.G., Maintenance treatment with quetiapine versus discontinuation after one year of treatment in patients with remitted first episode psychosis: randomised controlled trial, British Medical Journal. 2010, 341: c4024.
Chen E.Y.H., Hui C.L.M., Dunn E.L.W., Miao M.Y.K., Yeung W.S., Wong C.K., Chan W.F. and Tang W.N., Normalization of semantic categorization deficit in first-episode schizophrenia patients following symptomatic recovery: a three-year prospective longitudinal study, Schizophrenia Research. 2010, 117 (2-3): 292-293.
Cheung V., Chiu C.P.Y., Law C.W., Cheung C., Hui C.L.M., Chan K.K.S., Sham P.C., Deng Y., Tai K.S., Khong P.L., McAlonan G.M., Chua S.E. and Chen E.Y.H., Positive symptoms and white matter microstructure in never-medicated first episode schizophrenia, Psychological Medicine. 2010, 40: 1-12.
Hui C.L.M., Chen E.Y.H., Dunn E.L.W., Miao M.Y.K., Yeung W.S., Wong C.K., Chan W.F. and Tang W.N., The association between semantic categorization deficit and symptoms in first-episode schizophrenia, Schizophrenia Research. 2010, 117 (2-3): 409-410.
Hui C.L.M., The impact of renamed schizophrenia in psychiatric practice in Hong Kong, 2009.
Tang Y.M., Chiu C.P.Y., Hui C.L.M., Chan K.K.S., Lam M.L.M., Chan K.W., Wong G.H.Y. and Chen E.Y.H., Clinical and cognitive correlates of perceived extent of recovery in Chinese patients with psychosis, Schizophrenia Research. 2010, 117 (2-3): 516.
Tang Y.M., Wong G.H.Y., Hui C.L.M., Lam M.L.M., Chiu C.P.Y., Chan K.W., Chung D.W.S., Tso S., Chan K.P.M., Yip K.C., Hung S.F. and Chen E.Y.H., Early intervention for psychosis in Hong Kong - the EASY programme, Early Intervention in Psychiatry. 2010, 4 (3): 214-219.
Tang Y.M., Lam M.L.M., Wong H.Y., Hui C.L.M., Chiu C.P.Y., Law C.W., Chung D.W.S., Tso S., Yip K.C., Chen E.Y.H. and Hung S.F., Time to a stop or a change in prescription of initial antipsychotic medication in first-episode schizophrenic patients: A naturalistic study, 2nd Schizophrenia International Research Society Conference (April 10-14, 2010), Florence, Italy. 2010.
Wong G.H.Y., Tao H.J., He Z., Liu H.H., Chiu C.P.Y., Chan K.W., Lam M.L.M., Hui C.L.M., Tang Y.M., Wang Y.H., Xue Z.M., Liu Z.N. and Chen E.Y.H., Delusions of reference, excessive top-down processing, and default mode network in first-episode schizophrenia, Schizophrenia Research. 2010, 117 (2-3): 491.


Researcher : Hui TCK
List of Research Outputs

So H.C., Fong P.Y., Chen R.Y.L., Hui T.C.K., Ng M.Y.M., Cherny S.S., Mak W.W., Cheung E.F.C., Chan R.C.K., Chen E.Y.H., Li T. and Sham P.C., Identification of Neuroglycan C and Interacting Partners as Potential Susceptibility Genes for Schizophrenia in a Southern Chinese Population, American Journal of Medical Genetics Part B (Neuropsychiatric Genetics). 2010, 153B (1): 103-113.


Researcher : Koh YW
List of Research Outputs

Chan C.Y., Lee A.M., Lam S.K., Leung K.Y., Chung K.F., Koh Y.W. and Tang C.S.K., Psychological abuse experiences are independently associated with disordered eating symptoms among pregnant women, Paper presented at the Hong Kong Psychological Society Annual Conference 2010 "Development challenges across Life Stages", Hong Kong, June 12, 2010.
Koh Y.W., Lee A.M., Leung K.Y., Chan C.Y., Tang C.S.K. and Chung K.F., Identifying Psychosocial Risk Factors for Mental Health and Psychosomatic Problems Among Expectant Fathers During Transition to Fatherhood, Paper presented at the American Psychological Science Annual Convention, Boston, May 27-30, 2010.


Researcher : Kwan SH
List of Research Outputs

Kwan S.H., Cherny S.S., Kung A.W.C. and Sham P.C., Novel Sib Pair Selection Strategy Increases Power in Quantitative Association Analysis, Behavior Genetics. 2010, 39 (5): 571-579.


Researcher : Lam MLM
Project Title:Subjective and Objective neuropsychological and neuroanatomical abnormalities in people with high risk of developing psychosis
Investigator(s):Lam MLM, Chen EYH, Chiu CPY, Chan KW, Hui CLM
Department:Psychiatry
Source(s) of Funding:Seed Funding Programme for Basic Research
Start Date:06/2009
Abstract:
Project Objectives: 1. To study the relationship between subjective and objective cognitive deficits in a group of high-risk individuals 2. To investigate if any candidate risk factors, such as psychopathology and neurobiological variables including neurocognitive deficits and structural brain changes influence transition rate to psychosis in the high risk group Key issues and Problems being addressed: Schizophrenia is serious and often affects young people. Up to now, the aetiology of schizophrenia remains unknown. Despite progress in the development of medication with fewer side-effects, the treatment often cannot alleviate the disability associate with this chronic form of illness. Deficit symptoms and cognitive impairment, which appear to be the greatest determinants of disability, remain largely beyond the reach of current forms of treatment (1). The treatment outcome is often poor and associated with extensive cost, burden, morbidity and mortality (2-5) The period precede the onset of schizophrenia has been termed the prodrome. Various retrospective studies have demonstrated that the pre-psychotic or prodromal period is characterised by non-specific symptoms such as depressed mood, anxiety, cognitive symptoms as well as sub-threshold psychotic symptoms (6-8). This prodromal period is often prolong, lasting from 2 to 5 years (9-12), and is associated with substantial levels of psychosocial impairment and disability (13,14). However, a major challenge has been to prospectively identify the prodromal phase, particularly given the non-specific nature of prodromal symptoms. McGorry et al. introduced the term “At Risk Mental State”, implying that a sub-threshold syndrome can be regarded as a risk factor for the subsequent development of psychosis, but that the onset of psychosis is not inevitable (13,14). Several studies conducted internationally in recent years using this criteria yielded conversion rates between 33% and 58% (15,16) . Using the “at risk mental state” criteria, 29% (18 out of 62) of the identified high-risk subjects developed psychosis within 6 months in the local setting.(17) Increasing consensus exists that the structure of brain is abnormal in major psychotic disorders, whether these abnormalities predate onset of illness and are relatively fixed over its course, or whether they are progressive remain controversial (18). Cognitive deficits are a core feature of established psychotic illnesses. Premorbid IQ is regarded as a risk factor for subsequent development of schizophrenia (19,20). However, the association between cognitive deficit and emerging psychosis in individuals found to be at high-risk for psychosis is less understood. Subtle subjectively experienced cognitive, vegetative and perceptual disturbances called “basic symptoms” have been described in prodromal phase (21-23). Deviant neuropsychological performance of subjects symptomatically at risk of first-episode psychosis has been shown in several domains including verbal memory and executive functions, sustained attention, processing speed and possibly spatial working memory (24,25). Furthermore, subtle, self-experienced cognitive perceptive disturbances have been shown to be predictive of later schizophrenia, and to be common within the psychotic spectrum (26). Subjective cognitive impairment was found to be the most commonly reported symptoms in the high risk group and was reported in all those who developed psychosis within 6 months locally, additionally, subjective cognitive impairment score was found to be significantly higher in the group that ultimately became psychotic (17). Another study showed that subjective and objective cognitive deficits are two distinct construct, which only weakly correlated in established schizophrenic patients in the local population (27).Yet, little is known about the possible association between subjective and objective cognitive disturbances in the prodromal phase. In summary, there are only limited prospective studies in the initial pre-psychotic phase worldwide, the search for robust predictors to schizophrenia only have begun past few years and the preliminary findings of these ongoing studies are inconsistent. I therefore propose to conduct this prospective naturalistic study not only to identify high-risk individuals who may then transit to psychosis but also to explore the interaction between self perceived and objectively measured neuropsychological deviances and neuroanatomical abnormalities in the high-risk individuals and their contributions in predicting the probability of transition to psychosis.


List of Research Outputs

Chan K.K.S., Hui C.L.M., Chiu C.P.Y., Lam M.L.M., Chan K.W., Lin J., Xu J., Tang Y.M., Wong G.H.Y., Longenecker J.M. and Chen E.Y.H., A 3-year prospective study of spontaneous eye-blink rate in first-episode schizophrenia: Relationships with neurocognitive functions and relapse, 2nd Schizophrenia International Research Society Conference (April 10-14, 2010), Florence, Italy. 2010.
Chan K.K.S., Wong G.H.Y., Hui C.L.M., Tang Y.M., Chan K.W., Lam M.L.M., Chiu C.P.Y. and Chen E.Y.H., Game Theoretical Approach to Theory of Mind Deficits in Schizophrenic Patients with Delusion(s) of Reference, Schizophrenia Research. 2010, 117 (2-3): 286.
Chan K.W., Chiu C.P.Y., Lam M.L.M., Hui C.L.M., Wong G.H.Y., Tang Y.M., Chan K.K.S. and Chen E.Y.H., Relationship of neurocognitive function and impairment of insight in first episode schizophrenia, Schizophrenia Research. 2010, 117 (2-3): 209.
Chang W.C., Tang Y.M., Chiu C.P.Y., Hui C.L.M., Lam M.L.M., Wong G.H.Y., Law C.W., Tso S., Chan K., Hung S.F., Chung D.W.S. and Chen E.Y.H., Gender differences in patients presented with first-episode psychosis in Hong Kong, Schizophrenia Research. 2010, 117 (2-3): 281-2.
Chen E.Y.H., Hui C.L.M., Lam M.L.M., Chiu C.P.Y., Law C.W., Chung D.W.S., Tso S., Pang E.P.F., Chan K.T., Wong Y.C., Mo F.Y.M., Chan K.P.M., Yao T.J., Hung S.F. and Honer W.G., Maintenance treatment with quetiapine versus discontinuation after one year of treatment in patients with remitted first episode psychosis: randomised controlled trial, British Medical Journal. 2010, 341: c4024.
Lam M.L.M., Preliminary Findings of Ultra High Risk Research, Local Scence, Hong Kong Early Psychosis Intervention Society Conferece: Prodrome and Beyond 301009. 2009.
Lam M.L.M., Pearson V., Ng R.M.K., Chiu C.P.Y., Law C.W. and Chen E.Y.H., What does recovery from psychosis mena? Perceptions of young first-episode patients, International Journal of Social Psychiatry. 2010, 2-9.
Lam M.L.M., 思覺失調潛伏期 阻止病發好時機, 醫學教室, Apple Daily (2010-6-2). 2010.
Tang Y.M., Chiu C.P.Y., Hui C.L.M., Chan K.K.S., Lam M.L.M., Chan K.W., Wong G.H.Y. and Chen E.Y.H., Clinical and cognitive correlates of perceived extent of recovery in Chinese patients with psychosis, Schizophrenia Research. 2010, 117 (2-3): 516.
Tang Y.M., Wong G.H.Y., Hui C.L.M., Lam M.L.M., Chiu C.P.Y., Chan K.W., Chung D.W.S., Tso S., Chan K.P.M., Yip K.C., Hung S.F. and Chen E.Y.H., Early intervention for psychosis in Hong Kong - the EASY programme, Early Intervention in Psychiatry. 2010, 4 (3): 214-219.
Tang Y.M., Lam M.L.M., Wong H.Y., Hui C.L.M., Chiu C.P.Y., Law C.W., Chung D.W.S., Tso S., Yip K.C., Chen E.Y.H. and Hung S.F., Time to a stop or a change in prescription of initial antipsychotic medication in first-episode schizophrenic patients: A naturalistic study, 2nd Schizophrenia International Research Society Conference (April 10-14, 2010), Florence, Italy. 2010.
Wong G.H.Y., Tao H.J., He Z., Liu H.H., Chiu C.P.Y., Chan K.W., Lam M.L.M., Hui C.L.M., Tang Y.M., Wang Y.H., Xue Z.M., Liu Z.N. and Chen E.Y.H., Delusions of reference, excessive top-down processing, and default mode network in first-episode schizophrenia, Schizophrenia Research. 2010, 117 (2-3): 491.


Researcher : Lam SSY
List of Research Outputs

Deng Y., Meyer U., Lam S.S.Y., Feldon J., Li Q., Wei R., Luk L., Chua S.E., Sham P.C., Wang Y. and McAlonan G.M., Prenatal immune challenge causes frontal-subcortical proteome changes relevant to schizophrenia and autism, The International Journal of Neuropsychopharmacol. 2010.


Researcher : Law ACK
Project Title:Discovering the missing links in Alzheimer's Disease: A nouvelle, multidirectional approach
Investigator(s):Law ACK, Chu LW, Chang RCC
Department:Psychiatry
Source(s) of Funding:Seed Funding Programme for Basic Research
Start Date:01/2008
Completion Date:07/2010
Abstract:
Alzheimer’s Disease (AD) is the most common form of “neurodegenerative” dementia, characterized by progressive memory loss, cognitive deterioration in multiple domains, various neuropsychiatric symptoms, and impairment of activities of daily living. The primary risk factor for AD is increasing age. Beginning at age 65, the prevalence of AD doubles every 5 years. Although the precise etiologic mechanism for AD is unknown, evidence indicates the accumulation of beta-amyloid protein results in calcium homeostasis disturbance, oxidative stress, excitotoxicity, apoptosis, dysfunctional neurotransmitter systems, and neuronal demise. There is currently no curative treatment for AD. The available pharmacotherapy could only temporarily slow disease progression. In addition to cognitive impairments, AD patients often exhibit neuropsychiatric symptoms such as apathy, depressed mood, hallucinations, and paranoia. The occurrences of these symptoms suggest that relationships exist between AD and psychiatric illnesses. Major depressive disorder (MDD) often occurs prior to or concurrently with the onset of AD. Recent studies have demonstrated that a MDD history is associated with increased hippocampal amyloid load and that there is reduced serotonin receptor subtypes in the AD brain. A MDD history is also associated with more rapid cognitive decline in AD patients. MDD could be casually linked to AD due to its neurotoxic effects such as hypothalamic-pituitary-adrenal axis-mediated cortisol elevation and decreased brainderived neurotrophic factor level. Psychosis has been consistently recognised as a distinct neuropsychiatric syndrome in AD. Studies have shown that a polymorphism in the neuregulin gene – implicated in the development of schizophrenia – is associated with psychosis in AD. The apolipoprotein ε (ApoE) 4 allele is a known genetic risk for late-onset AD. The carrier of this allele has been shown to have increased risk of psychosis during the course of AD. The region that is close to the presenilin-1 gene on chromosome 14 has been implicated in AD patients experiencing hallucinations in a linkage analysis study. Polymorphisms in dopamine and serotonin receptor subtypes appear to increase psychosis risks in AD patients. White matter changes in the bilateral frontal or parietooccipital region and left basal ganglia in AD brains are associated with delusional misidentification. Thus far, evidence undoubtedly indicates that links between AD and major psychiatric disorders exist but they are not well understood. Nitric oxide (NO) is a potent endogenous vasodilator. In the brain, in addition to controlling cerebral vasoactivity, NO is intimately involved in the glutamate-mediated memory consolidation process. Furthermore, NO is an immunological mediator released by astrocytes and microglia. Interestingly, NO has also been implicated in a number of neurological disorders, including AD. My previous research has demonstrated that NO synthase (NOS)- induced neurotoxicity is isoform-specific and that amyloid toxicity is mediated by NO. Moreover, NO-modulating agents have neuroprotective and neurorescuing effects against amyloid toxicity in vitro. These significant findings and the complicated relationship between NO and AD pathogenesis remain to be further elucidated. Double-stranded RNA protein kinase (PKR) is an interferon-induced protein kinase. It can be activated upon binding to double-stranded RNA. PKR plays an important role in immune response towards viral infections. It is a well-recognized component of the apoptotic pathway. Recently, PKR has been implicated in AD. It appears that amyloid accumulation is a key factor in abnormal PKR activation seen in AD. Furthermore, PKR and NO may have an intricate connection, thereby contributing to the AD process. Current knowledge in these areas is primitive. AD has an insidious onset. During its early stage, the patient may have subtle cognitive deficits that are mistakenly being attributed to “normal ageing”. Moreover, most AD patients do not seek initial medical attention and family members also frequently overlook the presenting symptoms. The Mini Mental Status Exam (MMSE) is the most commonly used clinical screening test for cognition. This test has a high reliability to screen for moderate to severe cognitive impairments, but notoriously poor in detecting milder cognitive deficits. Hence, a number of factors could lead to significant diagnostic delay, thereby impeding the intervention process. Traditional Chinese Medicine (TCM) has long been used in attempt to improve cognition and treat neuropsychiatric disorders. Gingko biloba and huperzine A has been used in AD treatment with variable results. Recently, a number of herbal remedies have been shown to provide significant cytoprotective effects against amyloid-induced neurotoxicity. In addition, TCM such as saponins and Curcuma longa have been used to treat MDD with effective results. As the links between AD and MDD are being investigated, the potentials of these and other Chinese medications for AD warrant further studies. Despite decades of intensive research, there are still many unanswered, yet critical, questions towards the understanding of AD. Due to the nature of the illness, the current awareness and diagnostic methods of AD remain unsatisfactory. There is no effective pharmacotherapy that could halt or reverse the disease process. As the aging population continues to rise globally, the dementia pandemic will undoubtedly carry extensive medical and socioeconomic impacts if no effective solutions are to be discovered in the near future. The proposed project aims to: 1. Investigate the pathogenesis of AD. Both NO and PKR have been implicated in amyloid neurotoxicity. They appear to play important roles in the “upstream” aspects of the “amyloid toxicity cascade”. The elucidation of these pathways could lead to the development of biomarkers and the identification of therapeutic targets, thereby providing means of enhanced detection and additional psychopharmacological agents for AD, respectively. 2. Explore clinical methods for early disease detection and screening. Mild cognitive impairment (MCI) describes a cognitive state intermediate between normal aging and dementia. Evidence indicates that approximately 15% of MCI patients would progress to meet dementia criteria annually. The Montreal Cognitive Assessment (MoCA) has recently been developed as a brief screening tool for patients with milder cognitive deficits. This screening test has excellent sensitivity and specificity in detecting mild AD and MCI. A revised “Hong Kong – Cantonese” version is to be developed and validated. 3. Examine the potential neuroprotective and neurorescuing properties of TCM and other pharmacological agents (including antidepressants and antipsychotics). 4. Study the putative links between AD and psychiatric disorders.


Project Title:18th European Congress of Psychiatry THE POTENTIAL EFFECTS OF ANTIDEPRESSANTS IN ATTENUATING SYNAPTIC DEGENERATION IN DEPRESSION AND ALZHEIMER’S DISEASE
Investigator(s):Law ACK
Department:Psychiatry
Source(s) of Funding:URC/CRCG - Conference Grants for Teaching Staff
Start Date:02/2010
Completion Date:03/2010
Abstract:
N/A


Project Title:Linking the blood and the brain: The involvement of endothelial cell dysfunction in dementia pathogenesis.
Investigator(s):Law ACK, Vanhoutte PMGR, Chang RCC
Department:Psychiatry
Source(s) of Funding:Seed Funding Programme for Basic Research
Start Date:06/2010
Abstract:
Purpose of the proposed project: The primary aim of the proposed study is to investigate the links between endothelial dysfunction and Alzheimer’s disease (AD) pathogenesis. Key issues and problems being addressed: AD is the leading cause of neurodegenerative dementia. The clinical hallmark of AD is insidious memory loss. As the disease progresses, difficulties in a number of cognitive domains and neuropsychiatric symptoms emerge. AD is not curable and the currently available pharmacotherapies show only limited efficacies. As aging is the primary risk factor for AD and the elderly population continues to increase globally, AD has generated enormous medico- and socio-economical burdens. In Hong Kong, recent data shows that approximately 10% of the over-seventy population has at least mild dementia (15). The endothelial blood vessel lining plays a crucial role in maintaining vascular homeostasis. Pathological aging of the endothelium causes endothelial dysfunction, which appears to be an early event that leads to atherosclerosis and thrombosis. These vascular abnormalities also occur in the cerebral circulation, causing either acute or chronic hypoperfusion of brain tissues. There is also accumulating evidence to indicate the involvement of vascular derangement in AD development (3,14). Moreover, microcirculatory and AD-related pathologies are likely to have synergistic effects in the progression of cognitive impairments. Cardiovascular diseases and AD are highly prevalent disorders in the late life that lead to significant morbidities. Thus far, the precise interactions between these entities remain unknown. Hence, research to elucidate the underlying mechanisms linking vascular dysfunction and AD is highly warranted, with the long-term goal in yielding potential preventative and therapeutic strategies for AD and vascular-related dementing syndromes. Background information: The cerebral accumulation of β-amyloid (Aβ) peptide is a histopathological hallmark for AD. Aβ is an enzymatic cleavage product of amyloid precursor protein (APP). Overproduction of Aβ due to excessive β- and γ-secretase APP cleavages and the subsequent Aβ accumulation are believed to be the initiating events for multiple neurotoxic pathways (21). Neurofibrillary tangles (NFT) are intraneuronal deposits that have been consistently found in the AD brain. The primary physiological function of tau protein is to maintain microtubule stability. In AD, Aβ-induced tau hyperphosphorylation leads to NFT formation, which causes neuronal death by various pathological mechanisms (10). Oxidative stress has been implicated in the development of a number of neurodegenerative disorders. Excessive production of reactive oxidative species (ROS) along with decreased synthesis of endogenous antioxidants would be detrimental to neuronal survival. For example, mitochondrial dysfunction can contribute to neuronal dismay by several means. During the process of adenosine tri-phosphate production in the electron transfer chain, ROS are produced as byproducts. In a compromised antioxidative defense system, these radicals cause a variety of cellular dysfunction by means of lipid, protein, and DNA oxidation. In the AD brain, increased lipid peroxidation has been observed. Cerebral protein oxidation – which leads to enzyme damage and subsequent neuronal dysfunction - has also been shown to be significantly higher in AD patients (19). When mitochondria fail to provide adequate energy, partial neuronal depolarization occurs. This would allow excessive calcium influx, thereby triggering pathological events (2,20). The endothelial lining of a blood vessel plays a crucial role in maintaining vasomotor tone by producing vasoactive substances. Nitric oxide (NO) is known to be the most important regulator of vascular tone (8). In the endothelium, NO is produced by endothelial nitric oxide synthase (eNOS) – one of the three NOS isoforms – in respond to acetylcholine, bradykinin, and mechanical shear stress. NO has also been shown to be potentially cellular-toxic via several mechanisms (7,16,24). NO is a free radical and can combine with superoxide anions to form peroxynitrite - another highly destructive radical moiety. NO could affect mitochondrial energy production by interrupting electron transfer, thereby leading to mitochondrial dysfunction. Recent evidence has indicated that increased mitochondrial fission is mediated through the NO-pathway (4). It is not known if this pathological process occurs in the endothelial cell. Aβ is considered as an important culprit for AD pathogenesis, with its deposition far precedes the onset of clinical symptoms. In cardiovascular disorders, endothelial dysfunction appears to be an early event that promotes further pathological circulatory changes (9,22). Chronic cerebral hypoperfusion and ischemia lead to the overexpression of beta-amyloid precursor protein cleaving enzyme 1 (BACE1) and exaggerated Aβ accumulation in animal studies and in the human hippocampus. At the cellular level, the endothelium – an integral part of the blood-brain barrier (BBB) – possesses receptor for advanced end glycation products (RAGE) and low-density lipoprotein receptor related protein 1 (LRP1), which have pivotal roles in Aβ clearance. In the AD brain, altered endothelial RAGE and LRP1 expressions have been implicated in the deranged Aβ transport across the BBB (1,5,6,13). These findings suggest the existence of a key link between endothelial dysfunction and Aβ regarding their roles in AD development. The current literature indicates that endothelium senescence and the resultant vasomotor disturbances are likely to be intimately involved in AD pathogenesis (12); however, the precise interactions between these entities and the associating signalling mechanisms are not understood. Hence, the proposed project will examine the putative links between endothelial dysfunction and AD histopathological hallmarks using a mechanistic approach. Objectives: 1. Study the effects of Aβ on endothelial cell viability and survival. 2. Examine the effects of Aβ on eNOS expression, NO production, and tau hyperphosphorylation in the endothelial cell. 3. Investigate if Aβ-induced toxicity is mediated through mitochondrial dysfunction and excessive oxidative stress. 4. Explore the effects of mitochondrial dysfunction on endothelial oxidative stress and Aβ uptake. 5. Investigate the effects of Aβ uptake regulation and eNOS expression modulation on endothelial cell viability and survival. Hypotheses: 1. Aβ will increase eNOS expression and subsequent NO production in a concentration-dependent manner. 2. Aβ will decrease endothelial viability and survival. 3. Mitochondrial dysfunction and excessive oxidative stress will disrupt Aβ uptake regulation. 4. Aβ uptake and eNOS expression modulations will improve endothelial viability.


List of Research Outputs

Lau K.W., Law A.C.K., Ip M.S.M. and Mak J.C.W., Blockage of serotonin receptor 2 attenuates cigarette-induced IL-8 release in human bronchial epithelial cells, American Journal of Respiratory and Critical Care Medicine. 2010, 181: A1399.
Lau K.W., Law A.C.K., Ip M.S.M. and Mak J.C.W., Involvement of Serotonin in Cigarette Smoke-Induced IL-8 Release in Airway Epithelial Cells, ATS 2010 International Conference, New Orleans, USA (May 14-19, 2010). 2010.
Lau K.W., Law A.C.K., Ip M.S.M. and Mak J.C.W., Involvement of serotoninergic system in cigarette-induced inflammatory responses in human bronchial epithelial cells, HKU 14th Research Postgraduate Symposium, Hong Kong (December 2-3, 2009). 2010.
Lau K.W., Law A.C.K., Ip M.S.M. and Mak J.C.W., Ketanserin Attenuates Cigarette-mediated Oxidative Stress In Human Bronchial Epithelial Cells, Hong Kong Medical Journal. 2010, 16 (Suppl. 1): 34.
Law A.C.K., "Practical pharmacotherapy of emotional and somatic symptoms in MDD & GAD., Wyeth Limited., 2009.
Law A.C.K., A discussion on approaches to tackle Alzheimer's disease, International Conference on Transcultural Psychiatry: Cultural Diversity, Social Change and Mental Health in China, Shanghai, China (April 18-20, 2010). 2010.
Law A.C.K., I Prefer Talking. Do you? Introducing a nouvelle psychotherapeutic modality., Hong Kong Hospital Authority. 2009.
Law A.C.K., Organizer and Facilitator for Professor James Kennedy's talk on, "New Developments in Molecular Genetics of Response and Side Effects of Psychiatric Medications", Scientific Symposium (June 11, 2010). 2010.
Law A.C.K., In: WC Chan, 癡呆症的評估及檢查, 愛在晚晴時 - 失智症照顧者指南. 2010.
Wuwongse S., Hung H.L., Law A.C.K. and Chang R.C.C., Corticosterone induced synaptic degeneration in depression and Alzheimer's disease, Collegium Internationale Neuro-Psychopharmacologicum (CINP) 2010 World Congress. 2010, P-09.
Wuwongse S., Chang R.C.C. and Law A.C.K., Exploriing the Connection between Depression and Dementia, HKU 14th Research Postgraduate Symposium, Hong Kong (December 2-3, 2009). 2010.
Wuwongse S., Law A.C.K. and Chang R.C.C., Investigating synaptic degeneration as common pathophysiological factor in depression and Alzheimer's disease, 11th International Geneva/Springfield Symposium on Advances in Alzheimer Therapy, March 24-27, 2010 Geneva. 2010, 87.
Wuwongse S., Chang R.C.C. and Law A.C.K., Investigation of synaptic degeneration in depression and Alzheimer's disease, 5th International Symposium on Healthy Aging. 2010, Page 52.
Wuwongse S., Chang R.C.C. and Law A.C.K., The potential effects of antidepressants in attenuating synaptic degeneration in depression and Alzheimer's disease, 18th European Congress of Psychiatry, Munich, Germany (February 28 - March 2, 2010). 2010.
Yeung W.F., Chung K.F., Zhang S.P., Yap T.G. and Law A.C.K., Electroacupuncture for Primary Insomnia: A Randomized Controlled Trial, Sleep. 2009, 32 (8): 1039-1047.


Researcher : Law CW
List of Research Outputs

Chang W.C., Tang Y.M., Chiu C.P.Y., Hui C.L.M., Lam M.L.M., Wong G.H.Y., Law C.W., Tso S., Chan K., Hung S.F., Chung D.W.S. and Chen E.Y.H., Gender differences in patients presented with first-episode psychosis in Hong Kong, Schizophrenia Research. 2010, 117 (2-3): 281-2.
Chen E.Y.H., Hui C.L.M., Lam M.L.M., Chiu C.P.Y., Law C.W., Chung D.W.S., Tso S., Pang E.P.F., Chan K.T., Wong Y.C., Mo F.Y.M., Chan K.P.M., Yao T.J., Hung S.F. and Honer W.G., Maintenance treatment with quetiapine versus discontinuation after one year of treatment in patients with remitted first episode psychosis: randomised controlled trial, British Medical Journal. 2010, 341: c4024.
Cheung V., Chiu C.P.Y., Law C.W., Cheung C., Hui C.L.M., Chan K.K.S., Sham P.C., Deng Y., Tai K.S., Khong P.L., McAlonan G.M., Chua S.E. and Chen E.Y.H., Positive symptoms and white matter microstructure in never-medicated first episode schizophrenia, Psychological Medicine. 2010, 40: 1-12.
Deng Y., McAlonan G.M., Cheung C., Chiu C.P.Y., Law C.W., Cheung V., Sham P.C., Chen E.Y.H. and Chua S.E., A naturalistic study of grey matter volume increase after early treatment in anti-psychotic naïve, newly diagnosed schizophrenia, Psychopharmacology. 2009, 206: 437-446.
Lam M.L.M., Pearson V., Ng R.M.K., Chiu C.P.Y., Law C.W. and Chen E.Y.H., What does recovery from psychosis mena? Perceptions of young first-episode patients, International Journal of Social Psychiatry. 2010, 2-9.
Ng R.M.K., Pearson V., Chen E.Y.H. and Law C.W., What does recovery from schizophrenia mean? Perceptions of medical students and trainee psychiatrists, International Journal of Social Psychiatry. 2010, 1-16.
Tang Y.M., Lam M.L.M., Wong H.Y., Hui C.L.M., Chiu C.P.Y., Law C.W., Chung D.W.S., Tso S., Yip K.C., Chen E.Y.H. and Hung S.F., Time to a stop or a change in prescription of initial antipsychotic medication in first-episode schizophrenic patients: A naturalistic study, 2nd Schizophrenia International Research Society Conference (April 10-14, 2010), Florence, Italy. 2010.


Researcher : Lee AM
Project Title:Psychosocial Group Therapy for Menopausal Women: A model for the non-pharmacological management of menopausal distress
Investigator(s):Lee AM
Department:Psychiatry
Source(s) of Funding:Centre on Behavioral Health Seed Funding Scheme - General Award
Start Date:07/2003
Abstract:
The study aims at developing and evaluating the efficacy of a psychosocial group therapy approach to the management of menopausal problems among Hong Kong women.


Project Title:A multidimensional longitudinal study of disordered eating attitudes and behaviours and its risk factors and outcome among pregnant women
Investigator(s):Lee AM, Leung KY, Lao TTH, Fong DYT
Department:Psychiatry
Source(s) of Funding:General Research Fund (GRF)
Start Date:04/2007
Completion Date:09/2009
Abstract:
Primary objectives: (1) To test the association of pregnancy-related risk factors (ambivalence towards pregnancy, pregnancy abuse, depression, and anxiety) with disordered eating attitudes and behaviours during pregnancy. (2) To test the association of pre-pregnancy related risk factors (pre-pregnant maladaptive eating attitudes and behaviours, and body dissatisfaction) with disordered eating attitudes and behaviours during pregnancy. Secondary objectives: (3) To establish the prevalence of disordered eating attitudes and behaviors among pregnant women in Hong Kong.


Project Title:Qualitative study of disordered eating and factors associated with its development among pregnant women in Hong Kong
Investigator(s):Lee AM, Leung SSK, Leung KY, Lam SK, Lao TTH, Fong DYT
Department:Psychiatry
Source(s) of Funding:Small Project Funding
Start Date:04/2008
Completion Date:03/2010
Abstract:
Eating disorders are recognized as important mental health problems with potentially serious physical and mental health consequences. It has been widely studied among adolescent females. However, despite the fact that eating disorders are most prevalent among women of childbearing ages (1,2), there is little systematic study of its prevalence, nature, and consequences among pregnant women. Nevertheless, preliminary evidence from the literature and existing theoretical conceptualization of eating disorders suggest that disordered eating attitudes and behaviours could be a significant public health problem among pregnant women. From the vantage point of empirical evidence, there are emerging case reports of eating disorders among pregnant women (2,3). A cross-sectional survey of 530 pregnant women also found that as many as 1 in 20 pregnant women were probable cases of eating disorders (4). Indeed, on theoretical grounds, pregnancy is a high-risk period for developing disordered eating problems, given the inevitable weight gain and body shape changes and the enormous developmental challenges faced by pregnant women. Hence, disordered eating among pregnant women deserves more serious and systematic investigation, especially given the nutritional and mental health implications of disordered eating on fetal development, birth outcome, and well-being of both the mother and the infant (3,5-8). Pregnancy is not only a period of bliss and joyful anticipation but also a period of developmental challenge and substantial stress. One of the many difficulties that pregnant women face is problem with eating and body image. Due to a variety of physiological and psychological factors, pregnancy leads to substantial changes in appetite, eating patterns, body weight, and body shape. Pregnancy also represents a major developmental transition with substantial role changes. The developmental challenges faced by pregnant women may place them at high risk for developing disordered eating problems, as studies of eating disorders among non-pregnant women have found that difficulties in negotiating developmental challenges contribute to the development of eating disorders (9). Pregnancy is thus a high-risk period during which women with psychological vulnerabilities may develop eating and body image problems in response to stressors brought about by pregnancy. The small number of studies on pregnant women mainly focused on women with pre-existing eating disorders and examined the impact of pregnancy on the course of the eating disorders (10-12). There is limited knowledge on the development of disordered eating during pregnancy among women without a history of eating disorders. Nevertheless, there is some preliminary evidence that pregnancy may precipitate the development of eating disorders. One case series of 23 patients with eating disorders described the development of eating disorders either during pregnancy or in the early postpartum period (3). None of these patients had a history of eating disorders before their pregnancies. Fairburn and colleagues, in their study of 100 pregnant women, also identified seven cases of de novo cases of clinical eating disorders during pregnancy, none of which were cases immediately prior to pregnancy although two had a history of eating disorders in the more distant past (2). Our recent work on pregnant women further showed that disordered eating is not uncommon among pregnant women. In our pilot study of 346 Chinese pregnant women, it was found that 4.1% of pregnant women sscored above sut-off on the Eating Attitude Test-26 (EAT-26) (13). Another study also found that 9.8% of pregnant women displayed varying degrees of disordered eating symptoms (14). However, little is known of the process of development of eating disorders during pregnancy, and the factors associated with its development. Findings from our pilot study revealed that the relationship between depression and anxiety on the one hand and disordered eating on the other was significant but very weak (r = .13, p < .05 for depression and disordered eating, and r = .17, p < .01 for anxiety and disordered eating).This suggests that other factors pertinent and specific to pregnancy may be implicated in the development of disordered eating during pregnancy. The weak association is unexpected as depression and anxiety are strongly associated with disordered eating among non-pregnant women (15,16), reflecting that the nature of disordered eating during pregnancy may be qualitatively different from that among non-pregnant adolescent women. Only a qualitative design can provide insight into the exact nature of disordered eating during pregnancy, and the specific factors that are involved in its development We submitted a grant proposal (entitled “A Multidimensional Longitudinal Study of Disordered Eating Attitudes and Behaviours and Its Risk Factors and Outcome among Pregnant Women” – ref no. HKU 7470/06H) to the Competitive Earmarked Research Grant Scheme in 2006 to conduct a prospective longitudinal study of disordered eating and its risk factors among pregnant women in Hong Kong. We proposed to adopt a combined quantitative and qualitative design comprising a large-scale survey of prevalence, course and pregnancy-specific risk factors of 1500 pregnant women, followed by in-depth interviews of those screened positive for disordered eating using the Eating Attitudes Test-26 (17). The proposal was funded but the budget was reduced. The amount granted was only adequate for covering the large-scale survey. Thus, in accepting the grant, we asked for permission to restrict the study to the survey component only. However, the qualitative component is of great value. It is only through the interviews that we could really understand the nature of the disordered eating experience of the pregnant women, the course of development of their disordered eating during pregnancy, and the factors involved in its development. The infrastructure is already there. All we need is an extra amount of money to conduct the qualitative interviews. Indeed, it would be a shame if we let the opportunity slip by. The survey arm enables us to identify those with disordered eating problems. If we do not catch this window of opportunity to conduct the qualitative interviews, we would need to start all over again with screening probable cases when we design another study in the future. The current proposed study aimed at capitalizing on and complementing the larger CERG study to gain in-depth information on the nature and course of disordered eating among pregnant women, and to identify pregnancy-specific risk factors associated with the development of disordered eating during pregnancy.


Project Title:Prevalence and risk factors for paternal depression and anxiety in the antenatal period
Investigator(s):Lee AM, Chung KF, Fong DYT, Law ACK, Leung KY
Department:Psychiatry
Source(s) of Funding:Small Project Funding
Start Date:02/2009
Abstract:
Depression among pregnant and postpartum women has been extensively studied, and is shown to be a clinically significant problem (1-5). Antenatal depression is also gaining research and clinical attention, given its prevalence and adverse impact on pregnancy outcomes and fetal development (6-11). The significance of anxiety among pregnant women is also increasingly recognized (6,9). In contrast, much less attention is paid to paternal mental health over the course of wife’s pregnancy and the postpartum. Nevertheless, pregnancy is evidently a shared life experience for the couple, and fathers, just like mothers, are subject to substantial stress. The mental health of both partners is also intricately and reciprocally related. It is, therefore, important to recognize the mental health implications of men’s adjustment to this major life transition, and to understand the relationship between fathers’ and mothers’ mental state as they face this shared life challenge. Studies on paternal postpartum depression are beginning to emerge in the literature, documenting the existence of the problem and highlighting the difficulties faced by fathers while adjusting to fatherhood (12,13). Knowledge in paternal mental health problems in the antenatal period is, however, pathetically lacking. The present study aims at estimating the prevalence of paternal depression and anxiety in the antenatal period, investigating the association between paternal and maternal antenatal depression and anxiety, identifying the risk factors of paternal antenatal depression and anxiety, and examining the extent to which paternal antenatal depression and anxiety predict paternal postpartum depression and anxiety. It is estimated that 10-20% of postpartum women suffer from postpartum depression (1,2). Postpartum depression not only affects the well-being of the mother but is also shown to be associated with long-lasting adverse effects on the offspring, including problems in emotional, behavioral, and cognitive development (3-5). Recently, research focus on antenatal depression is also increasing. Studies have found that as many as 7-20% of pregnant women suffer from antenatal depression (6-8). Our own study showed that more than one-third of pregnant women in Hong Kong had clinically significant depressive symptoms (9). There is increasing evidence that antenatal depression impacts negatively on pregnancy outcomes and fetal development, being associated with increased risk of preterm delivery, spontaneous abortion, need for operative deliveries, low birth weight, low Apgar scores, neonatal growth retardation, birth complications, and fetal death (10,11). Much less is known of fathers’ mental health as they face the challenges of parenthood. Fatherhood is, however, a demanding role which can undeniably bring about substantial stress. Like mothers, fathers need to adjust to role changes, increased responsibilities, lifestyle changes, financial burden, as well as worry about the health of their spouse and the fetus. While the wife is pregnant, the spouse very often also needs to take up a caregiving role which can be very demanding. The mental health repercussions of these stressors should not be overlooked. There is growing awareness that depression can affect fathers in the postnatal period. Different studies have established that a significant number of fathers experience postpartum depression, rendering it a “clinically meaningful phenomenon” (13). Reported rates of paternal postpartum depression ranged from 5.3% to 31.7% (12-17), with most commonly reported rates being in the range of 11 to 20% (13,15,16). As expected, paternal and maternal postpartum depression are significantly associated with each other within the couple unit (13,14). It is generally concluded that paternal postpartum depression is a significant problem but, like gender discrepancy in depression outside of reproductive events, is less prevalent than maternal postpartum depression (12,13). Paternal postpartum depression is not only important in its own right but is also important in terms of its impact on child development. Paternal postpartum depression has been shown to be independently associated with increased risk of psychiatric disorders in the children seven years later, after controlling for maternal postpartum depression, paternal education level, and paternal depression beyond the postpartum period (18). Data on paternal postpartum anxiety problems is much more limited but researchers have repeatedly called for more attention to this problem in order to understand the full range of mood problems experienced by postpartum fathers (12,19). Matthey et al found that including anxiety disorders in the assessment increased paternal postpartum psychiatric caseness by 31-130%, and urged for a re-orientation of focus on the full range of mood disorders in future research (19). Despite improved recognition of paternal mental health problems in the postpartum period, paternal depression and anxiety in the antenatal period remains under-recognized. There have been very few attempts to examine these problems. Preliminary evidence showed that depression affected 4.8-5.3% of fathers in the antenatal period (12,14), and is significantly associated with paternal postpartum depression (12). To the best of our knowledge, there are no studies on paternal anxiety in the antenatal period but rates are expected to be higher than those for depression, based on the picture in the postpartum period, as well as the comparative prevalence of depression and anxiety among mothers in the antenatal period. There is no available data in the literature on either depression or anxiety among Chinese fathers in the antenatal period. More systematic research in these areas is definitely needed. Our proposed study aims at filling these important knowledge gaps to achieve a better understanding of the mental health problems experienced by expectant fathers. The objectives of the proposed study are: 1. To describe the prevalence of paternal depression and anxiety, and to compare them against the rates among mothers 2. To examine the relationship between paternal and maternal depression and anxiety in the antenatal period 3. To identify demographic, clinical, and psychosocial risk factors for paternal depression and anxiety 4. To examine the association between paternal antenatal depression and anxiety and paternal postpartum depression and anxiety Hypotheses 1. An appreciable proportion of expectant fathers experience depression and anxiety, though the prevalence is lower than that among expectant mothers 2. Paternal depression and anxiety are significantly associated with maternal depression and anxiety 3. Based on risk factors of paternal postpartum depression and maternal antenatal depression and anxiety identified in the literature, it is hypothesized that paternal postpartum depression and anxiety are associated with the following risk factors: a. demographic risk factors: young age, lower socioeconomic status, history of psychiatric disorders b. clinical risk factors: maternal pregnancy complications and maternal antenatal depression and anxiety c. psychosocial risk factors: unwanted pregnancy, unplanned pregnancy, low self esteem, high perceived stress, low social support, and poor marital relationship 4. Paternal antenatal depression and anxiety are significant predictors of paternal postpartum depression and anxiety


List of Research Outputs

Chan C.Y., Lee A.M., Lam S.K., Leung K.Y., Chung K.F., Koh Y.W. and Tang C.S.K., Psychological abuse experiences are independently associated with disordered eating symptoms among pregnant women, Paper presented at the Hong Kong Psychological Society Annual Conference 2010 "Development challenges across Life Stages", Hong Kong, June 12, 2010.
Chiang V.C.L., Leung S.S.K., Lee A.M., Lam S.K., Fung S., Wong A.K.Y. and Yung W.K., A short antenatal cognitive-behavorial program to prevent postpartum depression and anxiety in Hong Kong (oral presentation), The 4th International Conference on Community Health Nursing Research (Health in Transition: Researching for the Future), Adelaide, Australia. 2009.
Koh Y.W., Lee A.M., Leung K.Y., Chan C.Y., Tang C.S.K. and Chung K.F., Identifying Psychosocial Risk Factors for Mental Health and Psychosomatic Problems Among Expectant Fathers During Transition to Fatherhood, Paper presented at the American Psychological Science Annual Convention, Boston, May 27-30, 2010.
Lam T.H., Yip P.S.F., Ngan H.Y.S., Lo L., Ho K.Y., Jao M., Lai F.C.Y., Lee A.M., Mok J.H.F., Ng M.L., Siu Y.M., Yau K. and Yip K.Y., Report on the Survey of Family Planning Knowledge, Attitude and Practice in Hong Kong 2007. Hong Kong, Family Planning Association of Hong Kong, 2009, pp 87.
Lam T.H., Yip P.S.F., Ngan H.Y.S., Lo L., Ho K.Y., Jao M., Lai F.C.Y., Lee A.M., Mok J.H.F., Ng M.L., Siu Y.M., Yau K. and Yip K.Y., The report of youth sexuality study 2006. Hong Kong, Family Planning Association of Hong Kong, 2009, 208pp.
Lee A.M., Adverse outcomes of antenatal depression and anxiety, Invited lecture given at the XXII European Congress of Perinatal Medicine, Granada, Spain, May 27, 2010. 2010.
Lee A.M., Antenatal Anxiety and Stress, Ming Pao, page D2, June 6, 2010. 2010.
Lee A.M., Antenatal and Postpartum Mental Health, RTHK Channel 1 - Ad Wiser (1-2pm), June 26, 2009. 2010.
Lee A.M., Chair, Organizing Committee, Hong Kong Psychological Society Annual Conference 2010 "Developmental Challenges across Life Stages". 2010.
Lee A.M., Depression, Broadcasted on Roadshow, August to October 2009. 2010.
Lee A.M., Depression, Broadcasted on TVB HD, April to May, 2010. 2010.
Lee A.M., Eating Disorders in Pregnancy (Sep 9, 2009), Annual Scientific Meeting of the Obstetrical & Gynaecological Society of Hong Kong. 2009.
Lee A.M., Ho J.W.C. and Chan C.L.W., Efficacy of psychosocial intervention in improving quality of life and psychological well-being of Chinese patients with colorectal cancer: A randomised controlled trial, Hong Kong Medical Journal. 2010, 16 (3): 20-24.
Lee A.M., Expert Consultant, Hong Kong Primary Care Foundation, PHUDA, 2010. 2010.
Lee A.M., Founding Panel Member, E-Motion Alliance, Hong Kong Primary Care Foundation 2010. 2010.
Lee A.M., Invited Speaker for lecture entitled "Interviewing Sklls for Cervical Smear Taking", Family Planning Association, May 30, 2010. 2010.
Lee A.M., Invited Workshop Speaker for workshop "Eating Disorders and Self-Esteem Problems among Adolescents" (Hospital Authority - Jardines Mindset Health in Mind Youth Mental Health Promotion Programme) April 24, 2010. 2010.
Lee A.M., Premenstrual Syndrome and Lifestyle Factors, Oriental Daily HKU Health Column, September 13, 2009. 2010.
Lee A.M., Chu L.W., Chong C.S.Y., Chan S.Y., Lam K.S.L. and Lam T.P., Relationship Between Symptoms of Androgen Deficiency and Psychological Factors and Quality of Life among Chinese Men., International Journal of Andrology.. 2009.
Lee A.M., Research Subcommittee Member, Family Planning Association 2010. 2010.
Lee A.M., Reviewer, General Hospital Psychiatry. 2010.
Lee A.M., Role of Family Support in Helping Women with Antenatal Anxiety and Depression, Oriental Daily HKU Health Column, May 7, 2010. 2010.
Lee A.M., Scientific Officer, Council of the Hong Kong Psychological Society, 2010. 2010.
Lee A.M., Stress and stress management, Invited lecture given at the RC Lee Hall High Table Dinner, HKU, November 17, 2009. 2009.
Lo P.H.Y., Chan J.S.M., Ho T.H., Cheung K.M., Lee A.M. and Chan C.L.W., Antecedents of prolonged anxiety and depression among breast and colorectal cancer survivors in Hong Kong: Implications for survivorship needs, International Conference on Promoting Chronic Care. Hong Kong, 2010.


Researcher : Lee PWH
Project Title:A study of risk factors for exposure to AIDS in high risk adolescent Chinese females
Investigator(s):Lee PWH
Department:Psychiatry
Source(s) of Funding:Council for the AIDS Trust Fund - General Award
Start Date:04/1997
Abstract:
To study the prevailing pattern of knowledge, practice and attitudes towards sexual intimacy and behaviours in teenage secondary school female students; to study common misconceptions and risks of teenage secondary school students towards developing STDs and AIDs; to study factors associated with increased risk for exposure to STDs and AIDs.


Project Title:Psychological adjustment and stresses of nurses working in acute hospital
Investigator(s):Lee PWH
Department:Psychiatry
Source(s) of Funding:Other Funding Scheme
Start Date:06/1997
Abstract:
To study the prevalence of psychological malaise in a representative group of registered nurses working in acute general hospital; to identify factors associated with increases stress and strain in registered nurses in acute general hospital.


Project Title:The psychosocial outcomes and well-being of living related donors involved in liver transplantation surgery: a follow-up study of risk factors, resilience, and outcome predictors
Investigator(s):Lee PWH, Fan ST, Fung ASM
Department:Psychiatry
Source(s) of Funding:Small Project Funding
Start Date:11/2003
Abstract:
To trace the natue and course of psycholsocial adjustment of living related donors through a retrospective study on their adjustment in the pre-transplanation, post-transplantation and rehabilitation phases; to identify areas of concerns, difficulties, physical malaise, and psychosocial distress in donors during the different phases of the transplantation procedure and its rehabilitation; to study the relationship between pre-transplantation variables of the living related donors and their levels of post-transplantation functioning and adjustment; to identify predictors of high-risk characteristics and situations likely to be encountered by living related donors and consider ways of reducing such risks; on the basis of data gathered and analyzed, to consider cost-effective avenues, format and focus of psychosocial interventions to enable potential living related donors to achieve an all round better immediate and long-term outcome; to look into the differences in decision making processes and adjustment of living related donors with different relationship with the recipients.


List of Research Outputs

Chu L.W., Chan I., Lee P.W.H., Li S.W. and Yu G.K.K., Effects of cognitive function and depressive mood on the quality of life in Chinese Alzheimer's disease patients in Hong Hong, Geriatrics and Gerontology International. 2010, 1-8.
Kwan T.T.C., Tam K.F., Lee P.W.H., Lo S.S.T., Chan K.K.L. and Ngan H.Y.S., De-stigmatising human papillomavirus in the context of cervical cancer: a randomised controlled trial, Psycho-Oncology. 2010, 1-11.
Lam C.L.K., Fong D.Y.T., Chin W.Y., Lee P.W.H., Lam T.P. and Lo Y.Y.C., Brief problem-solving treatment in primary care (pst-pc) was not more effective than placebo for elderly patients screened positive of psychological problems, International Journal of Geriatric Psychiatry. 2009.
Lam C.L.K., Chin W.Y., Lee P.W.H., Lo Y.Y.C., Fong D.Y.T. and Lam T.P., Unrecognized Psychological Problems Impair Quality of Life and Increase Consultation Rates in Chinese Elderly Patients, Int J Geriatr Psychiatry. 2009, 24 (Aug): 979-989.
Luk K.D.K., Wan T., Wong Y.W., Cheung K.M.C., Chan Y.K., Cheng A., Kwan M., Law K., Lee P.W.H. and Cheing G.L.Y., A multidisciplinary functional restoration program for patients with chronic back pain, International Society for the Study of the Lumbar Spine Annual Meeting, Auckland, New Zealand, April 13-17, 2010.


Researcher : Leung MK
List of Research Outputs

Leung M.K., Cheung C., Yu K.K.K., Yip B.H.K., Sham P.C., Li Q., Chua S.E. and McAlonan G.M., Gray Matter in First-Episode Schizophrenia Before and After Antipsychotic Drug Treatment. Anatomical Likelihood Estimation Meta-analyses With Sample Size Weighting, Schizophrenia Bulletin . 2009, 16.


Researcher : Leung YK
List of Research Outputs

Ong K.L., Tso A.W.K., Leung Y.K., Cherny S.S., Sham P.C., Cheung B.M.Y. and Lam K.S.L., Relationship of genetic variants in gene encoding adrenomedullin with hypertension and dysglycaemia in Hong Kong Chinese, 13th Annual Scientific Meeting of the Institute of Cardiovascular Science and Medicine, Co-morbidity Hypertension / Diabetes: which one do we treat, Dec 2009, Hong Kong. 2009.


Researcher : Li Q
Project Title:White matter alterations following antipsychotic drug treatment in a neurodevelopmental animal model of schizophrenia
Investigator(s):Li Q, McAlonan GM, Chua SE
Department:Psychiatry
Source(s) of Funding:Small Project Funding
Start Date:11/2008
Completion Date:05/2010
Abstract:
Schizophrenia is a disorder characterized by deteriorating ability to function in everyday life and by some combination of positive symptoms (hallucinations, delusions, thought disorder, movement disorder), and negative symptoms (deficits of social interaction, emotional expressions, and working memory). Most positive symptoms are treatable by the administration of antipsychotic drugs. The two main classes of drugs are the ‘typical’ and ‘atypical’ antipsychotics. Typical antipsychotic drugs, which include haloperidol, chlorpromazine and fluphenazine, are primarily dopamine D2 receptor antagonists, while the ‘atypical’ antipsychotics, such as clozapine, risperidone and olanzapine, have a range of affinities for several different neurotransmitter receptors in addition to those for dopamine (Miyamoto et al., 2005; Arranz and de Leon, 2007). However, uncertainty surrounds the mechanism of action of antipsychotic drugs, with no clear insight into the pathways of action. The major existing theories of schizophrenia have been developed by exploring the mechanisms of action of these antipsychotic drugs. For example, the ‘dopamine hypothesis’ of schizophrenia, formulated over 30 years ago, proposes that the hyperactivity of dopaminergic neurotransmission causes symptoms of schizophrenia. However it has become clear that other, additional systems, components and/or factors are required to explain the complex nature of this disease (Carlsson and Lindqvist, 1963; van Rossum, 1966). Multiple lines of evidence now converge to implicate oligodendrocyte and myelin dysfunction in schizophrenia. Studies have shown reductions in white matter volume, decreased anisotropy of white matter tracts, regressive changes in oligodendrocyte structure and density, and decreases in the expression of myelin-related genes in the brains of schizophrenia patients (Hakak et al., 2001; Davis et al., 2003). Consistent with this, our MRI studies of the first-episode schizophrenia patients shows that fronto-temporal and subcortical-limbic circuits are morphologically abnormal (Chua et al., 2007). Besides, our group has demonstrated that antipsychotic drugs modify fronto-temporal-striatal brain morphology in patients with schizophrenia in parallel with symptom remission (Chua et al 2008). More recent evidence clearly indicates that white matter’s role as the ‘backbone’ of neural networks in the brain is also critical to many important aspects of higher cognitive functioning including attention, executive functioning, and visual-spatial processing (Filley, 1998). Furthermore, high-throughput gene expression analyses have revealed a down-regulation of a number of myelin/oligodendrocyte-related genes, including, myelin associated glycoprotein (MAG), myelin oligodendrocyte glycoprotein (MOG), transferring (TF), and claudin 11 (CLDN11) (Aston et al., 2005). Newer, so-called atypical antipsychotic drugs have better effects on cognitive function in schizophrenia than older typical drugs. However, the extent to which these medications effect white matter indices is not clear and cannot easily be directly established in clinical studies on man. A useful mouse model of schizophrenia is based on evidence that maternal bacterial and viral infections during pregnancy are associated with psychosis in the offspring later in adult or post-pubescent life (Brown et al., 2004). The model involves prenatal immune challenge by the synthetic analogue of double-stranded RNA, polyriboinosinic-polyribocytidilic acid (PolyI:C). Poly (I:C) exposure of pregnant mice on gestation day 9 (GD 9, corresponding to the end of first and early second trimester human pregnancy) leads to behavioural impairments in multiple domains which mimic the spectrum of psychopathology seen in schizophrenia patients (Meyer et al., 2007). It is thought that PolyI:C leads to a pronounced but time-limited production of pro-inflammatory cytokines after administration (Meyer et al., 2008). The consensus is that this inflammatory response at a sensitive time in prenatal development triggers persistent neurodevelopmental changes and constitutes an extremely useful tool to examine the neurobiological basis of schizophrenia. Antipsychotic drugs appear to alter the expression of myelin/oligo-related genes in response to antipsychotic treatment on normal mice (Narayan et al., 2007). However, a detailed investigation of the effects of antipsychotic medications using a neurodevelopmental model of schizophrenia has not been done yet. The overall objective is to translate our findings in man to an animal model in order to directly examine the impact of antipsychotic drugs on brain tissue in schizophrenia. It is hypothesized that anti-psychotic medication exerts an effect on white matter systems.We will quantify the expression in three specific white matter regions in mice, such as, the corpus callosum, the anterior commissure, and the internal capsule (Narayan et al., 2007). The mode of action of either the atypical antipsychotic medication, clozapine, or typical antipsychotic, haloperidol will be explored using the polyI:C mouse model in the following ways: 1. Characterising the extent to which behavioural impaiments in the mouse model can be reversed by antipsychotic treatment. 2. Measuring the morphological changes in brain tissue (including changes in markers for oligodendrocytes, astrocytes, and microglia) after antipsychotic treatment by immunohistochemistry. 3. Analysis of the relationship between 1. and 2.


Project Title:The 15th Biennial Winter Workshop in Psychoses Prenatal immune challenge as a risk factor for white matter microstructural anomalies relevant to schizophrenia
Investigator(s):Li Q
Department:Psychiatry
Source(s) of Funding:URC/CRCG - Conference Grants for Teaching Staff
Start Date:11/2009
Completion Date:11/2009
Abstract:
N/A


List of Research Outputs

Chen M.X., Li Q., Pan F.A.N.G. and Ao L.J., Animal models of post-stroke depression and assessment of its face validity (review), Chinese Journal of Behavioral Medical Science & neuroscience. 中華行為醫學與腦科學雜誌, 2010, (in press).
Chen M.X., Li Q., McAlonan G.M., Rudd J.A. and Ao L., The time of prenatal stress challenge influences the specificity of behavioral abnormality exhibited in neurodevelopmental disorders, The International Journal of Neuropsychopharmacol. 2010.
Deng Y., Meyer U., Lam S.S.Y., Feldon J., Li Q., Wei R., Luk L., Chua S.E., Sham P.C., Wang Y. and McAlonan G.M., Prenatal immune challenge causes frontal-subcortical proteome changes relevant to schizophrenia and autism, The International Journal of Neuropsychopharmacol. 2010.
Leung M.K., Cheung C., Yu K.K.K., Yip B.H.K., Sham P.C., Li Q., Chua S.E. and McAlonan G.M., Gray Matter in First-Episode Schizophrenia Before and After Antipsychotic Drug Treatment. Anatomical Likelihood Estimation Meta-analyses With Sample Size Weighting, Schizophrenia Bulletin . 2009, 16.
Li Q. and Yew D.A.V.I.D., A Review of the Dopamine System in the Animal Models of Attention-Deficit Hyperactivity Disorder, In: Editors: Stuart M. Gordon and Aileen E. Mitchell, NOVA Publishers. 2009, pp.167-188.
Li Q., Application for University of Hong Kong/China Medical Board Grant. 2009 Nov, awarded., HKU China Affairs Office. 2009.
Li Q., Wong J.H., Lu G.A.N.G., Antonio G.E., Yeung D.K., Ng T.B., Forster L.E. and Yew D.T., Gene expression of synaptosomal-associated protein 25 (SNAP-25) in the prefrontal cortex of the spontaneously hypertensive rat (SHR), Biochim Biophys Acta, Molecular Basis of Disease. 2009, 1792 (8): 766-76.
Li Q., Cheung C., Wei R., Wong P., McAlonan G.M. and Wu E., Oral presentation: Prenatal immune challenge as a risk factor for white matter microstructural anomalies relevant to schizophrenia, The 15th Biennial Winter Workshop in Psychoses 2009, Barcelona, Espana (November 15-18, 2009). 2010.
Li Q., Cheung C., Hui E.S., Feldon J., Meyer U., Chung S.K., Chua S.E., Sham P.C., Wu E.X. and McAlonan G.M., Prenatal Immune Challenge Is an Environmental Risk Factor for Brain and Behavior Change Relevant to Schizophrenia: Evidence from MRI in a Mouse model, PLOSone. 2009, e6354.
Li Q., Cheung C., Cheung V., Zhang X., Wei R., Wong P., You Y.Q., Hui E., Chua S.E., McAlonan G.M. and Wu E.X., The timing of prenatal immune challenge determines the extent of postnatal white matter microstructural anomalies in a mouse model of schizophrenia, The International Journal of Neuropsychopharmacol. 2010.
Li Q., URC/CRCG-Conference Grants for Teaching Staff. 2009 July 17, awarded., The University of Hong Kong. 2009.
Li Q., Cheung C., Wei R., Cheung V., Hui E.S., You Y., Wong P., Chua S.E., McAlonan G.M. and Wu E.X., Voxel-based analysis of postnatal white matter microstructure in mice exposed to immune challenge in early or late pregnancy, Neurolmage. 2010, 52(1): 1-8.
McAlonan G.M., Li Q., Cheung C., Wei R., Chua S.E., Sham P.C. and Wu E.X., Evidence that prenatal infection is a risk factor for brain and behaviour changes relevant to schizophrenia and autism, 41st European Brain and Behaviour Society Meeting (EBBS), Rhodes 2009. (September 13-18, 2009). 2010.
McAlonan G.M., Li Q., Cheung C., Wei R., Cheung V., Hui E.S.K., Wong P., Chua S.E. and Wu E.X., Oral presentation: The Timing of Prenatal Immune Challenge Determines the Extent of White Matter Microstructural Anomalies Relevant to Autism, International Meeting for Autism Research (IMFAR) Chicago 2010. (May 19-25, 2010). 2010.
McAlonan G.M., Li Q. and Cheung C., The timing and specificity of prenatal immune risk factors for autism modeled in the mouse (review), Neurosignals. 2010, (in press).
McAlonan G.M., Cheung C., Li Q., Cheung V., Hui E.S.K., Wei R., Wong P., Chua S.E. and Wu E.X., The timing of prenatal immune challenge determines the extent of white matter microstructural anomalies relevant to schizophrenia, The 2nd Biennial Schizophrenia International Research Society Conference (SIRS), Florence, Italy, 2010. (April 9-16, 2010). 2010.
Wei R., Li Q., Chua S.E. and McAlonan G.M., Prenatal exposure to valproic acid induces a dose dependent impairment in sensorimotor gating in a mouse model of autism, The International Journal of Neuropsychopharmacol. 2010.
Wong N.K., Wong A.O.L., Lau N.K.C., Wei R., Zhang X., Li Q. and McAlonan G.M., Prenatal exposure of mice to a maternal immune challenge leads to changes in expression of genes regulating white matter, The International Journal of Neuropsychopharmacol. 2010.
Yu H.L., Li Q., Wang D.F., Shi L.I.N., Mak Y.T., Lu G.A.N.G., Shun L.I.N., Pan F.A.N.G. and Yew D.T., Chronic Ketamine Abuse Causes Dysfunctions of Different Brain Areas Relevant to Neuro - developmental Psychiatric Disorders: Evidence from fMRI in a primate model, The International Journal of Neuropsychopharmacology. 2010, P01.046.


Researcher : Lin J
List of Research Outputs

Chan K.K.S., Hui C.L.M., Chiu C.P.Y., Lam M.L.M., Chan K.W., Lin J., Xu J., Tang Y.M., Wong G.H.Y., Longenecker J.M. and Chen E.Y.H., A 3-year prospective study of spontaneous eye-blink rate in first-episode schizophrenia: Relationships with neurocognitive functions and relapse, 2nd Schizophrenia International Research Society Conference (April 10-14, 2010), Florence, Italy. 2010.


Researcher : Longenecker JM
List of Research Outputs

Chan K.K.S., Hui C.L.M., Chiu C.P.Y., Lam M.L.M., Chan K.W., Lin J., Xu J., Tang Y.M., Wong G.H.Y., Longenecker J.M. and Chen E.Y.H., A 3-year prospective study of spontaneous eye-blink rate in first-episode schizophrenia: Relationships with neurocognitive functions and relapse, 2nd Schizophrenia International Research Society Conference (April 10-14, 2010), Florence, Italy. 2010.


Researcher : Mak KY
Project Title:Program enhancement for the mental-ill patients at the S.K. Yee Mental Health Resource and Rehabilitation Centre
Investigator(s):Mak KY, Wong MMC, Mak-Lieh F, Yau EFY
Department:Psychiatry
Source(s) of Funding:S.K. Yee Medical Foundation - General Award
Start Date:09/2000
Abstract:
To facilitate psychiatric patients to return to work and re-integrate into society through widening the present service scope by providing sufficient equipment to meet the increasing demand in work training and offer wider range of therapeutic programs to improve the domestic living skill of patients; to provide professional development and training to psychiatrists and paramedical staff in Hong Kong and China.




Researcher : McAlonan GM
Project Title:Neurodevelopment of schizophrenia. Mapping predisposition, prodrome and conversion to disease-state in the mouse model.
Investigator(s):McAlonan GM, Wu EX, Chua SE, Li Q, Sham PC
Department:Psychiatry
Source(s) of Funding:Seed Funding Programme for Basic Research
Start Date:05/2008
Completion Date:05/2010
Abstract:
Schizophrenia is thought to be hereditary but not all cases can be accounted for by genetics alone. There is strong evidence that environmental factors, especially during prenatal life, contribute to the disorder. In landmark studies, our team member Prof Sham reported the strong association of schizophrenia with prenatal influenza virus exposure [1-3]. However, while there is consensus that the onset of abnormalities in schizophrenia is likely to be early in fetal life, there follows a clinically ‘latent’ phase and patients only present with overt clinical signs of disease in early adulthood. By this first presentation, we have shown that significant structural changes in brain are already apparent [4, 5], suggesting that the brain has undergone maldevelopment during childhood and adolescence. While brain maldevelopment leading up to a diagnosis of schizophrenia may be unrecognised, some patients can be identified during a ‘prodromal’ phase of illness. During the prodrome, patients have subtle or mild symptoms which do not fulfil criteria for psychosis (e.g. delusions and hallucinations). It is thought that prodromal features may progressively worsen until diagnostic criteria for schizophrenia is reached. Therefore, if we intervene at this earlier stage in disease development, it might be possible to prevent or a least lessen the impact of full-blown psychosis ([6, 7], since a longer duration of untreated psychosis is associated with poor outcomes [8]. Of course identifying and treating such patients has the effect of ‘labelling’ them. This in itself raises ethical issues, as not all patients suspected of being in a prodrome phase of schizophrenia will go on to develop the disorder [9]. More problematic is the issue of treatment choices for these patients. Anti-psychotic drug treatments in particular can have significant side effects, potentially causing motor, metabolic, cardiac and immunological abnormalities. Despite these many challenges, preventing schizophrenia, or at least improving outcome with early treatment, is an extremely important goal. What is needed is to explore the clinically ‘silent’ period of brain development though childhood and adolescence and identify key pathological steps leading to prodrome and final conversion to full-blown disease. Given the problems of studying this protracted time course in man, an animal model becomes invaluable. Rodent biology (genes, development and physiology) is remarkably similar to man, but a disease process can be observed in vivo from beginning to end in a reasonably short time. Therefore the aim of the present study is to map the neurodevelopmental sequelae of prenatal viral immune challenge from delivery, through to disease expression in adulthood using a mouse model. In particular we wish to address the ‘symptom free’ phase of brain maldevelopment in schizophrenia and find what turns predisposition into disease. We will use the mouse to model brain changes in offspring exposed to a viral analogue, poly I:C. This model has extensively studied by our collaborator, Prof Feldon and shown to very closely parallel many neurochemical and cognitive features of schizophrenia. While delusions and hallucinations cannot be tested directly in a mouse, the mechanism underlying formation of psychotic symptoms is suggested to be a basic impairment in ignoring irrelevant information leading to multiple inappropriate associations between cues. Attaching inappropriate significance or trying to rationalize these experiences, in turn is thought to lead to delusions. In patients with schizophrenia and in the mouse model, impaired filtering of stimuli or ‘sensorimotor gating’ is reflected by disruption of prepulse inhibition of startle response (PPI) and associative learning errors made in the mouse model match errors made by patients [10-12]. Also, like patients with schizophrenia, mice exposed to an immune challenge prenatally have an increased sensitivity to psychostimulants such as amphetamine [10, 11]. However, this mouse model of schizophrenia is most appealing because the development of psychopathology follows a similar trajectory to man. That is, behavioural impairments are not evident until adulthood [13]. The only clue of underlying brain maldevelopment is a heightened sensitivity to amphetamine in immature mice. In the present study our objective is to isolate key steps in neurodevelopmental trajectory of schizophrenia. We will use prenatal immune challenge in the mouse to model the impact of fetal exposure on post-natal brain structure, behaviour, and protein expression. We will examine the model at 3 time-points (childhood, adolescence and adulthood) using MRI, DTI, amphetamine challenge and PPI.


Project Title:King's/HKU Fellowship Awards 2008-09
Investigator(s):McAlonan GM
Department:Psychiatry
Source(s) of Funding:King's/HKU Fellowship Awards
Start Date:09/2008
Abstract:
To visit the Institute of Psychiatry in King's College London to undertake a collaborative study on brain biology in autism from a multi-ethnic perspective and to establish practical brain imaging and genomics protocols for use in Hong Kong and U.K.


Project Title:Preventing schizophrenia-like phenotype in the mouse model
Investigator(s):McAlonan GM, Chua SE, Lam SSY, Wang Y, Li Q
Department:Psychiatry
Source(s) of Funding:Seed Funding Programme for Basic Research
Start Date:03/2010
Abstract:
We propose an innovative prospective study of preventative treatment in a mouse model of schizophrenia. We will use a well validated maternal immune activation (MIA) model of schizophrenia. The MIA model simulates neuranatomical, neurochemical and behavioural features of schizophrenia (Meyer, Murray et al. 2007; Meyer, Engler et al. 2008; Li, Cheung et al. 2009). Moreover, it even replicates the natural history of the disease with impairments not fully evident until adulthood (Meyer, Schwendener et al. 2006). It is based on strong evidence that exposure to immune challenge during prenatal life increases the risk of schizophrenia (Brown and Susser 2002; Babulas, Factor-Litvak et al. 2006; Brown 2006; Brown, Deicken et al. 2009). Prenatal infection may precipitate long-term autoimmune response in the brain (Wright, Gill et al. 1993; Wright and Murray 1993; Wright, Sham et al. 1996) and immune mechanisms potentially explain glutamergic and dopaminergic disregulation characteristic of schizophrenia (Muller and Schwarz 2006). Consistent with this, schizophrenia is associated with: (i) persistent immunological anomalies and altered balance of inflammatory cytokines (Cazzullo, Sacchetti et al. 2002; Drzyzga, Obuchowicz et al. 2006; Crespo-Facorro, Carrasco-Marín et al. 2008); (ii) autoimmunity (Gilvarry, Sham et al. 1996; Gaughran and Hucklebridge 2002; Steiner, Bielau et al. 2008); (iii) increased microglia (the brain’s inflammatory cell) (Steiner, Bielau et al. 2008); (iv) improvement with anti-inflammatory drugs (Muller, Riedel et al. 2005; Muller and Schwarz 2008). In addition all effective anti-psychotic drugs have immune suppressant action (Bian, Kato et al. 2008). Thus, there is consensus that prenatal exposure to inflammatory mediators increases risk of schizophrenia and that chronic deregulation of the immune response occurs in schizophrenia. Therefore we propose an investigation of anti-inflammatory treatment for schizophrenia in the MIA mouse model. Objective We will test the hypothesis that anti-inflammatory treatment alleviates the phenotype in the MIA model of schizophrenia. n-3 polyunsaturated fatty-acids (PUFA) occur naturally in fish oils. These have a robust anti-inflammatory action and may improve schizophrenia (Peet, Brind et al. 2001; Peet 2003; Peet 2004). Decreased membrane PUFA in schizophrenia has been linked to immunological abnormalities (Yao, Sistilli et al. 2003; Yao, van Kammen et al. 2004). The impact of PUFA dietary enrichment during adolescence in mice previously exposed to prenatal immune challenge will be examined. Effectiveness of the intervention will be measured in the following ways: a. Behavioural phenotyping - sensorimotor gating (stimulus filtering) Abnormalities in sensorimotor gating are a recognised endophenotype of schizophrenia (Braff, Geyer et al. 2001). Mice exposed to MIA have sensorimotor gating deficits (measured in the prepulse inhibition of startle programme; PPI). PPI is a conventional translational task widely used in the human and animal schizophrenia literature (Braff, Geyer et al. 2001; Geyer, Krebs-Thomson et al. 2001; Kumari, Antonova et al. 2008). b. Cellular basis – Immunohistology and proteomics. Immunological studies report increased activated microglia in post-mortem brain samples of patients who suffered from schizophrenia. In our pilot studies we have also evidence of increased in activated microglial in MIA mouse brain. In addition we have reported increased ventricular size in mice exposed to MIA, along with reduction in white matter markers (Li et al. 2009a; 2009b). Ventriculomegaly is the most consistent brain structural finding in schizophrenia and we have shown that white matter connections are disrupted in schizophrenia (Chua et al. 2007; 2002; Cheung et al., 2008). Proteomics investigation allows examination of the dynamic cellular mechanisms underlying response to treatment. Our clinical and animal proteomics studies to date point towards dysregulation of intracellular pathways involved in oxidative stress in schizophrenia.


Project Title:International Meeting for Autism Research (IMFAR) 2010 The timing of prenatal immune challenge determines the extent of white matter microstructural abnormalities revelent to Autism
Investigator(s):McAlonan GM
Department:Psychiatry
Source(s) of Funding:URC/CRCG - Conference Grants for Teaching Staff
Start Date:05/2010
Completion Date:05/2010
Abstract:
N/A


List of Research Outputs

Chan R.C., Di X., McAlonan G.M. and Qong Q.Y., Brain Anatomical Abnormalities in High-Risk Individuals, First-Episode, and Chronic Schizophrenia: An Activation Likelihood Estimation Meta-analysis of Illness Progression. , Schizophrenia Bulletin. 2009.
Chen M.X., Li Q., McAlonan G.M., Rudd J.A. and Ao L., The time of prenatal stress challenge influences the specificity of behavioral abnormality exhibited in neurodevelopmental disorders, The International Journal of Neuropsychopharmacol. 2010.
Cheung C., Yee Y.F., Fung G.C.M., Yu K.K.K., Yao N., You Y., McAlonan G.M. and Chua S.E., MRI brain scan study of minor physical anomalies to aid the early diagnosis of autism, International College of Neuropsychopharmacology 2010, Hong Kong (June 6-10, 2010). 2010.
Cheung C., Chua S.E., Cheung V., Khong P.L., Tai K.S., Wong T.K.W., Ho T.P. and McAlonan G.M., White matter fractional anisotrophy differences and correlates of diagnostic symptoms in autism, Journal of Child Psychology and Psychiatry. 2009, 50: 1102-1112.
Cheung V., Chiu C.P.Y., Law C.W., Cheung C., Hui C.L.M., Chan K.K.S., Sham P.C., Deng Y., Tai K.S., Khong P.L., McAlonan G.M., Chua S.E. and Chen E.Y.H., Positive symptoms and white matter microstructure in never-medicated first episode schizophrenia, Psychological Medicine. 2010, 40: 1-12.
Deng Y., McAlonan G.M., Cheung C., Chiu C.P.Y., Law C.W., Cheung V., Sham P.C., Chen E.Y.H. and Chua S.E., A naturalistic study of grey matter volume increase after early treatment in anti-psychotic naïve, newly diagnosed schizophrenia, Psychopharmacology. 2009, 206: 437-446.
Deng Y., Meyer U., Lam S.S.Y., Feldon J., Li Q., Wei R., Luk L., Chua S.E., Sham P.C., Wang Y. and McAlonan G.M., Prenatal immune challenge causes frontal-subcortical proteome changes relevant to schizophrenia and autism, The International Journal of Neuropsychopharmacol. 2010.
Fung G.C.M., Catani M., Chua S.E., Murphy D.G.M. and McAlonan G.M., Cerebellar Feedback Projections in Autism Spectrum Disorder, 14th Research Postgraduate Symposium (December 2-3, 2009). 2010.
Fung G.C.M., Fung Y.Y., Cheung C., You Y., McAlonan G.M. and Chua S.E., MRI measurement of intracranial MPAs (minor physical anomalies) in autism, International Meeting of Autism Research 2010, Philadephia, USA. (May 20-22, 2010). 2010.
Hu Z.Y., Chan R.C.K. and McAlonan G.M., Maturation of social attribution skills in typically developing children: An investigation using the Social Attribution Task and a modified version for young children., Behavioral and Brain Functions. 2010, in press.
Leung M.K., Cheung C., Yu K.K.K., Yip B.H.K., Sham P.C., Li Q., Chua S.E. and McAlonan G.M., Gray Matter in First-Episode Schizophrenia Before and After Antipsychotic Drug Treatment. Anatomical Likelihood Estimation Meta-analyses With Sample Size Weighting, Schizophrenia Bulletin . 2009, 16.
Li Q., Cheung C., Wei R., Wong P., McAlonan G.M. and Wu E., Oral presentation: Prenatal immune challenge as a risk factor for white matter microstructural anomalies relevant to schizophrenia, The 15th Biennial Winter Workshop in Psychoses 2009, Barcelona, Espana (November 15-18, 2009). 2010.
Li Q., Cheung C., Hui E.S., Feldon J., Meyer U., Chung S.K., Chua S.E., Sham P.C., Wu E.X. and McAlonan G.M., Prenatal Immune Challenge Is an Environmental Risk Factor for Brain and Behavior Change Relevant to Schizophrenia: Evidence from MRI in a Mouse model, PLOSone. 2009, e6354.
Li Q., Cheung C., Cheung V., Zhang X., Wei R., Wong P., You Y.Q., Hui E., Chua S.E., McAlonan G.M. and Wu E.X., The timing of prenatal immune challenge determines the extent of postnatal white matter microstructural anomalies in a mouse model of schizophrenia, The International Journal of Neuropsychopharmacol. 2010.
Li Q., Cheung C., Wei R., Cheung V., Hui E.S., You Y., Wong P., Chua S.E., McAlonan G.M. and Wu E.X., Voxel-based analysis of postnatal white matter microstructure in mice exposed to immune challenge in early or late pregnancy, Neurolmage. 2010, 52(1): 1-8.
McAlonan G.M., Li Q., Cheung C., Wei R., Chua S.E., Sham P.C. and Wu E.X., Evidence that prenatal infection is a risk factor for brain and behaviour changes relevant to schizophrenia and autism, 41st European Brain and Behaviour Society Meeting (EBBS), Rhodes 2009. (September 13-18, 2009). 2010.
McAlonan G.M., Li Q., Cheung C., Wei R., Cheung V., Hui E.S.K., Wong P., Chua S.E. and Wu E.X., Oral presentation: The Timing of Prenatal Immune Challenge Determines the Extent of White Matter Microstructural Anomalies Relevant to Autism, International Meeting for Autism Research (IMFAR) Chicago 2010. (May 19-25, 2010). 2010.
McAlonan G.M., Li Q. and Cheung C., The timing and specificity of prenatal immune risk factors for autism modeled in the mouse (review), Neurosignals. 2010, (in press).
McAlonan G.M., Cheung C., Li Q., Cheung V., Hui E.S.K., Wei R., Wong P., Chua S.E. and Wu E.X., The timing of prenatal immune challenge determines the extent of white matter microstructural anomalies relevant to schizophrenia, The 2nd Biennial Schizophrenia International Research Society Conference (SIRS), Florence, Italy, 2010. (April 9-16, 2010). 2010.
McAlonan G.M., Translating between clinical studies and laboratory mouse models in autism research, Joint Annual Scientific Meeting of the Hong Kong Society of Neurosciences and the Biophysical Society of Hong Kong. (June 7-8, 2010). 2010.
Wei R., Li Q., Chua S.E. and McAlonan G.M., Prenatal exposure to valproic acid induces a dose dependent impairment in sensorimotor gating in a mouse model of autism, The International Journal of Neuropsychopharmacol. 2010.
Wong N.K., Wong A.O.L., Lau N.K.C., Wei R., Zhang X., Li Q. and McAlonan G.M., Prenatal exposure of mice to a maternal immune challenge leads to changes in expression of genes regulating white matter, The International Journal of Neuropsychopharmacol. 2010.


Researcher : Ng ML
Project Title:Chaos in psychotherapy
Investigator(s):Ng ML
Department:Psychiatry
Source(s) of Funding:Department of Psychiatry - General Award
Start Date:09/1998
Completion Date:08/2010
Abstract:
To look for chaos patterns in the communication procedures in psychotherapy using mathematical or physical modelling.


Project Title:Violence on male genitalia - a ten year review of cases in Hong Kong
Investigator(s):Ng ML
Department:Psychiatry
Source(s) of Funding:Other Funding Scheme
Start Date:05/2002
Abstract:
To review and investigate into the demographic, psychological and social characteristics of the victims and the offenders involved in cases of violent male genital injury in the last ten years in Hong Kong.


List of Research Outputs

Lam T.H., Yip P.S.F., Ngan H.Y.S., Lo L., Ho K.Y., Jao M., Lai F.C.Y., Lee A.M., Mok J.H.F., Ng M.L., Siu Y.M., Yau K. and Yip K.Y., Report on the Survey of Family Planning Knowledge, Attitude and Practice in Hong Kong 2007. Hong Kong, Family Planning Association of Hong Kong, 2009, pp 87.
Lam T.H., Yip P.S.F., Ngan H.Y.S., Lo L., Ho K.Y., Jao M., Lai F.C.Y., Lee A.M., Mok J.H.F., Ng M.L., Siu Y.M., Yau K. and Yip K.Y., The report of youth sexuality study 2006. Hong Kong, Family Planning Association of Hong Kong, 2009, 208pp.
Lee W.Y., Ng M.L., Yung J.W. and Cheung B.K.L., Capturing children's response to parental conflict and making use of it, Family Process. Wiley-Blackwell, 2010, 49: 43-58.


Researcher : Sham PC
Project Title:Optimal design of genome-wide association studies for multifactorial diseases
Investigator(s):Sham PC, Ng MKP, Tang NLS
Department:Psychiatry
Source(s) of Funding:General Research Fund (GRF)
Start Date:01/2007
Completion Date:12/2009
Abstract:
To focus on the following issues in the design of genome-wide association studies: (1) multi-stage, multi-platform study designs; (2) function-informed selection of tag SNPs and haplotype tagging; to quantitative evaluation of subject informativeness; marker-based derivation of homogeneous sub-populations.


Project Title:Replication study of susceptibility genes for colorectal cancer
Investigator(s):Sham PC, Ho JWC, Cheng KK
Department:Medical Faculty
Source(s) of Funding:Small Project Funding
Start Date:10/2007
Abstract:
To conduct replication studies in the Hogn Kong Chinese population of potential suscepstibility genes identified by whole-genome association studies performed in European populations.


Project Title:Genome-wide association study of schizophrenia
Investigator(s):Sham PC, Chen EYH, Chen RYL, Cherny SS, Tam PKH
Department:Medical Faculty
Source(s) of Funding:General Research Fund (GRF)
Start Date:01/2008
Abstract:
To identify susceptibility loci for schizophrenia by a genome-wide association screen using 500 case-control pairs and 500 case-parents trios; to examine the possible impact of the detected susceptibility genes on disease outcome in a sample of 130 schizophrenic patients who have been studied since the onset of psychosis.


Project Title:Genomics
Investigator(s):Sham PC
Department:Medical Faculty
Source(s) of Funding:Seed Funding for Strategic Research Theme
Start Date:06/2008
Completion Date:05/2011
Abstract:
n/a


Project Title:Visiting Research Professors Scheme 2009-10
Investigator(s):Sham PC
Department:Medical Faculty
Source(s) of Funding:Visiting Research Professors Scheme
Start Date:09/2009
Abstract:
To support the appointment of Professor Michael Q. Zhang as Visiting Research Professor in the Department of Psychiatry and SRT on Genomics.


Project Title:The 59th Annual Meeting of the American Society of Human Genetics A RET founder mutation in Chinese Hirschsprung’s patients
Investigator(s):Sham PC
Department:Medical Faculty
Source(s) of Funding:URC/CRCG - Conference Grants for Teaching Staff
Start Date:10/2009
Completion Date:10/2009
Abstract:
N/A


List of Research Outputs

Cherny S.S., Tang S.M., Sribudiani Y., Miao X., So M.T., Sham P.C., Tam P.K.H., Garcia-Barcelo M.M. and Hofstra R.M., Fine mapping of Hirschsprung's disease loci in 9q31 (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009.
Cheung B.M.Y., Ong K.L., Tso A.W.K., Cherny S.S., Sham P.C., Lam T.H. and Lam K.S.L., Gamma-glutamyl transaminase level predicts the development of hypertension., Presented at the Hong Kong College of Cardiology 18th Annual Scientific Congress, May 14-16, Hong Kong, 2010. 18: 33.
Cheung B.M.Y., Ong K.L., Tso A.W.K., Lam K.S.L., Cherny S.S. and Sham P.C., Using glycosylated hemoglobin to define the metabolic syndrome in United States adults., Presented at the Hong Kong College of Cardiology 18th Annual Scientific Congress, May 14-16, Hong Kong, 2010. 18: 33.
Cheung C.Y.Y., Tso A.W.K., Cheung B.M.Y., Xu A., Ong K.L., Law S.C., Sham P.C. and Lam K.S.L., A genetic variant near the GNPDA2 gene is associated with the metabolic syndrome in Hong Kong Chinese., 5th International Symposium on Healthy Aging. 2010.
Cheung C.Y.Y., Tso A.W.K., Sham P.C., Xu A., Ong K.L., Cheung B.M.Y. and Lam K.S.L., Implication of the obesity-associated genetic variants identified from recent genome-wide association studies in Hong Kong Chinese., 15th Medical Research Conference, HKU. Hong Kong Medical Journal.. 2010, 16: 15.
Cheung V., Chiu C.P.Y., Law C.W., Cheung C., Hui C.L.M., Chan K.K.S., Sham P.C., Deng Y., Tai K.S., Khong P.L., McAlonan G.M., Chua S.E. and Chen E.Y.H., Positive symptoms and white matter microstructure in never-medicated first episode schizophrenia, Psychological Medicine. 2010, 40: 1-12.
Cheung Y.Y., Tso A.W.K., Cheung B.M.Y., Xu A., Ong K.L., Fong H.Y., Wat N.M.S., Janus E.D., Sham P.C. and Lam K.S.L., Obesity susceptibility genetic variants identified from recent genome-wide association studies: implications in a chinese population., J Clin Endocrinol Metab. . 1403, 2010, 95: 1395.
Ching C.Y.J., Chan Y.K., Lee H.L.E., Xu M.S., Ting K.P., So T.M., Sham P.C., Leung G.M., Peiris J.S.M. and Khoo U.S., Significance of the myxovirus resistance A (MxA) gene -123C>a single-nucleotide polymorphism in suppressed interferon beta induction of severe acute respiratory syndrome coronavirus infection, J Infect Dis. 2010, 201(12): 1899-908.
Cornes B.K., Tang S.M., Leon Y.Y., Hui K.J.W.S., So M.T., Miao X., Cherny S.S., Sham P.C., Tam P.K.H. and Garcia-Barcelo M.M., Haplotype analysis reveals a possible founder effect of RET mutation R114H for Hirschsprung's disease in the Chinese population, PLoS One. 2010, 5 (6): e10918.
Deng Y., McAlonan G.M., Cheung C., Chiu C.P.Y., Law C.W., Cheung V., Sham P.C., Chen E.Y.H. and Chua S.E., A naturalistic study of grey matter volume increase after early treatment in anti-psychotic naïve, newly diagnosed schizophrenia, Psychopharmacology. 2009, 206: 437-446.
Deng Y., Meyer U., Lam S.S.Y., Feldon J., Li Q., Wei R., Luk L., Chua S.E., Sham P.C., Wang Y. and McAlonan G.M., Prenatal immune challenge causes frontal-subcortical proteome changes relevant to schizophrenia and autism, The International Journal of Neuropsychopharmacol. 2010.
Garcia-Barcelo M.M., Yeung M.Y., Miao X.P., Tang S.M., Chen G., So M.T., Ngan E.S.W., Lui V.C.H., Chen Y., Liu X., Hui K.J.W.S., Li L., Guo W.H., Sun X.B., Tou J.F., Chan K.W., Wu X.Z., Song Y., Chan D., Cheung K.M.C., Chung P.H.Y., Wong K.K.Y., Sham P.C., Cherny S.S. and Tam P.K.H., Genome-wide association study identifies a susceptibility locus for biliary atresia on 10q24.2, Human Molecular Genetics. 2010, 19 (14): 2917-2925.
Garcia-Barcelo M.M., Tang W.Y., Miao X., Tang S.M., So M.T., Leon Y.Y., Sham P.C., Cherny S.S. and Tam P.K.H., Identification of rare variants in the NRG1 gene of Hirschsprung's patients (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009.
Hao K., Luk J.M.C., Lee P.Y., Mao M., Zhang C., Ferguson M.D., Lamb J., Dai H., Ng I.O.L., Sham P.C. and Poon R.T.P., Predicting prognosis in hepatocellular carcinoma after curative surgery with common clinicopathologic parameters, BMC Cancer. 2009, 9: 389.
Kao Y.P.P., Chan D., Cheah K.S.E., Cheung K.M.C., Ho D.W.H., Karppinen J., Leong J.C.Y., Yip S.P., Song Y. and Sham P.C., Genome-wide Association Study of Degenerative Disc Disease (DDD), 14th Research Postgraduate Symposium, December 2 & 3, 2009, The University of Hong Kong. 2009.
Khoo U.S., Chan Y.K., Ching C.Y.J., Chan V.S.F., Ip Y.C., Yam L., Chu C.M., Lai S.T., So K.M., Wong T.Y., Chung P.H., Yip S.P., Sham P.C., Leung G.M., Lin C.L. and Peiris J.S.M., Functional role of ICAM-3 polymorphism in genetic susceptibility to SARS infection, Hong Kong Med Journal. 2009, 26-9.
Kung A.W.C., Xiao S., Cherny S.S., Li H.Y., Gao Y., Tso G., Lau K., Luk K.D.K., Liu J.M., Cui B., Zhang M.J., Zhang Z.L., He J.W., Yue H., Xia W.B., Luo L.M., He S.L., Kiel D.P., Karasik D., Hsu Y.H., Cupples L.A., Demissie S., Styrkarsdottir U., Halldorsson B.V., Sigurdsson G., Thorsteinsdottir U., Stefansson K., Richards B., Zhai G., Soranzo N., Valdes A., Spector T.D. and Sham P.C., Association of JAG1 with Bone Mineral Density and Osteoporotic Fractures: A Genome-wide Association Study and Follow-up Replication Studies, American Journal of Human Genetics. 2010, 86 (2): 229-239.
Kwan S.H., Cherny S.S., Kung A.W.C. and Sham P.C., Novel Sib Pair Selection Strategy Increases Power in Quantitative Association Analysis, Behavior Genetics. 2010, 39 (5): 571-579.
Leung M.K., Cheung C., Yu K.K.K., Yip B.H.K., Sham P.C., Li Q., Chua S.E. and McAlonan G.M., Gray Matter in First-Episode Schizophrenia Before and After Antipsychotic Drug Treatment. Anatomical Likelihood Estimation Meta-analyses With Sample Size Weighting, Schizophrenia Bulletin . 2009, 16.
Li Q., Cheung C., Hui E.S., Feldon J., Meyer U., Chung S.K., Chua S.E., Sham P.C., Wu E.X. and McAlonan G.M., Prenatal Immune Challenge Is an Environmental Risk Factor for Brain and Behavior Change Relevant to Schizophrenia: Evidence from MRI in a Mouse model, PLOSone. 2009, e6354.
McAlonan G.M., Li Q., Cheung C., Wei R., Chua S.E., Sham P.C. and Wu E.X., Evidence that prenatal infection is a risk factor for brain and behaviour changes relevant to schizophrenia and autism, 41st European Brain and Behaviour Society Meeting (EBBS), Rhodes 2009. (September 13-18, 2009). 2010.
Ngan E.S.W., Garcia-Barcelo M.M., Yip B.H.K., Sham P.C., Lui V.C.H. and Tam P.K.H., Hedgehog-notch induced premature gliogenesis of neural crest: a cause of Hirschsprung disease, International Society for Stem Cell Research, the 8th Annual Meeting, Moscone West, San Francisco, U.S.A. 16-19 June 2010.
Ong K.L., Tso A.W.K., Cherny S.S., Sham P.C., Lam K.S.L., Jiang C.Q., Thomas G.N., Lam T.H. and Cheung B.M.Y., A genetic variant in the gene encoding fibrinogen beta chain predicted development of hypertension in Chinese men, Thrombosis and Haemostasis. 2010, 103 (4): 728-735.
Ong K.L., Tso A.W.K., Cherny S.S., Sham P.C., Lam K.S.L., Jiang C.Q., Thomas G.N., Lam T.H. and Cheung B.M.Y., Adiponectin gene polymorphisms, plasma adiponectin level and persistent hypertension in Hong Kong Chinese, British Pharmacological Society Winter Meeting, Dec 2009, London, UK. 2009.
Ong K.L., Tso A.W.K., Cherny S.S., Sham P.C., Lam K.S.L., Jiang C.Q., Thomas G.N., Lam T.H. and Cheung B.M.Y., Association of a genetic polymorphism in the gene encoding fibrinogen beta chain with hypertension in Hong Kong Chinese., 15th Medical Research Conference, HKU. Hong Kong Medical Journal.. 2010, 16: 51.
Ong K.L., Tso A.W.K., Leung Y.H., Xu A., Cherny S.S., Sham P.C., Lam K.S.L. and Cheung B.M.Y., C-reactive protein as a predictor of hypertension in the Hong Kong cardiovascular risk prevalence study (CRISPS) cohort, Presented at the International Congress of Cardiology, Hong Kong, February 26-28, 2010.
Ong K.L., Tso A.W.K., Leung Y.H., Cherny S.S., Sham P.C., Cheung B.M.Y. and Lam K.S.L., Relationship of genetic variants gene encoding adrenomedullin with hypertension and dysglycaemia in Hong Kong Chinese, Annual Scientific Meeting of Hong Kong Society of Endocrinology. 2009.
Ong K.L., Tso A.W.K., Leung Y.H., Cherny S.S., Sham P.C., Cheung B.M.Y. and Lam K.S.L., Relationship of genetic variants in gene encoding adrenomedullin with hypertension and dysglycaemia in Hong Kong Chinese., 15th Medical Research Conference, HKU. Hong Kong Medical Journal.. 2010, 16: 50.
Ong K.L., Tso A.W.K., Leung R.Y., Cherny S.S., Sham P.C., Cheung B.M.Y. and Lam K.S.L., Relationship of genetic variants in gene encoding adrenomedullin with hypertension and dysglycaemia in Hong Kong Chinese, Annual Scientific Meeting and Annual General Meeting of Hong Kong Society of Endocrinology, Metabolism and Reproduction, Nov 2009, Hong Kong. 2009.
Ong K.L., Tso A.W.K., Cherny S.S., Sham P.C., Lam T.H., Lam K.S.L. and Cheung B.M.Y., Relationship of liver enzymes with hypertension in Hong Kong Chinese., 5th International Symposium on Healthy Aging. 2010.
Ong K.L., Tso A.W.K., Lam K.S.L., Cherny S.S., Sham P.C. and Cheung B.M.Y., Using glycosylated haemoglobin to define the metabolic syndrome in United States adults, Diabetes Care. 2010.
Ong K.L., Tso A.W.K., Lam K.S.L., Cherny S.S., Sham P.C. and Cheung B.M.Y., Using glycosylated hemoglobin to define the metabolic syndrome in United States adults., 5th International Symposium on Healthy Aging. 2010.
Sham P.C., Cornes B.K., Tang S.M., Leon Y.Y., So M.T., Tam P.K.H. and Garcia-Barcelo M.M., A RET founder mutation in Chinese Hirschsprung's patients (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009.
So H.C., Cherny S.S. and Sham P.C., Evaluating Variance in Liability Explained by Individual Genetic Variants and Relationship to Individualized Risk Prediction, Paper presented at the 18th Annual Meeting of the International Genetic Epidemiology Society, Honolulu, Hawaii, USA, October 10-20, 2009.
So H.C., Fong P.Y., Chen R.Y.L., Hui T.C.K., Ng M.Y.M., Cherny S.S., Mak W.W., Cheung E.F.C., Chan R.C.K., Chen E.Y.H., Li T. and Sham P.C., Identification of Neuroglycan C and Interacting Partners as Potential Susceptibility Genes for Schizophrenia in a Southern Chinese Population, American Journal of Medical Genetics Part B (Neuropsychiatric Genetics). 2010, 153B (1): 103-113.
Song Y., Tang L.F., Cheung C.L., Sham P.C., McClurg P., Smith D.K., Tanner J.A., Su A.I., Cheah K.S.E. and Kung A.W.C., Genome-wide haplotype association mapping in mice identifies a genetic variant in CER1 associated with bone mineral density and fracture in southern Chinese women, The American Society of Human Genetics 59th Annual Meeting, Honolulu, Hawaii. 2009.
Tang S.M., Sribudiani Y., Miao X., de Vries A.R., Burzynski G., So M.T., Leon Y.Y., Yip B.H.K., Osinga J., Hui K.J.W.S., Verheij J.B.G.M., Cherny S.S., Tam P.K.H., Sham P.C., Hofstra R.M.W. and Garcia-Barcelo M.M., Fine mapping of the 9q31 Hirschsprung's disease locus, Human Genetics. 2010, 127(6): 675-683.
Tang S.M., Garcia-Barcelo M.M., Cherny S.S., Sham P.C. and Tam P.K.H., Genome-wide profile of copy number variants for Hirschsprung's disease (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009.
Xiao S., Sham P.C. and Kung A.W.C., Periostin Gene is Associated with BMD Variation and Risk of Vertebral Fracture, The 31st Annual Meeting of the American Society for Bone and Mineral Research, Denver, Colorado, USA. 2009.
Yang S., Agrawal K.R., Lam T.W., Sham P.C., Cheah K.S.E. and Wang J.J., Novel Profile Hidden Markov Model to Predict MicroRNAs and their Targets Simutaneously, 14th Research Postgraduate Symposium, The University of Hong Kong, December 2-3. 2009.
Yang W., Shen N., Ye D.Q., Liu Q., Qian X.X., Hirankarn N., Pan H.F., Mok C.C., Chan D.T.M., Wong R.W.S., Lee K.W., Wong S.N., Leung A.M.H., Li X.P., Avihingsanon Y., Wong C.M., Lee T.L., Ho M.H.K., Lee P.P.W., Chang Y.K., Li P.H., Li R., Zhang L., Wong W.H.S., Ng I.O.L., Lau W.C.S., Sham P.C., Lau Y.L. and Asian Lupus Genetics Consortium A.L.G.C., Genome-wide association study in Asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosus. , PLoS Genetics. 2010, 6: e1000841.
Yip B.H.K., Ngan E.S.W., Garcia-Barcelo M.M., Cherny S.S., Tang S.M., Sham P.C. and Tam P.K.H., Quantifying epistasis between two sets of signaling pathway genes by canonical correlation analysis: with application on Hirschsprung's disease (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009.


Researcher : So HC
List of Research Outputs

So H.C., Cherny S.S. and Sham P.C., Evaluating Variance in Liability Explained by Individual Genetic Variants and Relationship to Individualized Risk Prediction, Paper presented at the 18th Annual Meeting of the International Genetic Epidemiology Society, Honolulu, Hawaii, USA, October 10-20, 2009.
So H.C., Fong P.Y., Chen R.Y.L., Hui T.C.K., Ng M.Y.M., Cherny S.S., Mak W.W., Cheung E.F.C., Chan R.C.K., Chen E.Y.H., Li T. and Sham P.C., Identification of Neuroglycan C and Interacting Partners as Potential Susceptibility Genes for Schizophrenia in a Southern Chinese Population, American Journal of Medical Genetics Part B (Neuropsychiatric Genetics). 2010, 153B (1): 103-113.


Researcher : Tang SM
List of Research Outputs

Cherny S.S., Tang S.M., Sribudiani Y., Miao X., So M.T., Sham P.C., Tam P.K.H., Garcia-Barcelo M.M. and Hofstra R.M., Fine mapping of Hirschsprung's disease loci in 9q31 (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009.
Cornes B.K., Tang S.M., Leon Y.Y., Hui K.J.W.S., So M.T., Miao X., Cherny S.S., Sham P.C., Tam P.K.H. and Garcia-Barcelo M.M., Haplotype analysis reveals a possible founder effect of RET mutation R114H for Hirschsprung's disease in the Chinese population, PLoS One. 2010, 5 (6): e10918.
Garcia-Barcelo M.M., Yeung M.Y., Miao X.P., Tang S.M., Chen G., So M.T., Ngan E.S.W., Lui V.C.H., Chen Y., Liu X., Hui K.J.W.S., Li L., Guo W.H., Sun X.B., Tou J.F., Chan K.W., Wu X.Z., Song Y., Chan D., Cheung K.M.C., Chung P.H.Y., Wong K.K.Y., Sham P.C., Cherny S.S. and Tam P.K.H., Genome-wide association study identifies a susceptibility locus for biliary atresia on 10q24.2, Human Molecular Genetics. 2010, 19 (14): 2917-2925.
Garcia-Barcelo M.M., Tang W.Y., Miao X., Tang S.M., So M.T., Leon Y.Y., Sham P.C., Cherny S.S. and Tam P.K.H., Identification of rare variants in the NRG1 gene of Hirschsprung's patients (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009.
Sham P.C., Cornes B.K., Tang S.M., Leon Y.Y., So M.T., Tam P.K.H. and Garcia-Barcelo M.M., A RET founder mutation in Chinese Hirschsprung's patients (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009.
Tang S.M., Sribudiani Y., Miao X., de Vries A.R., Burzynski G., So M.T., Leon Y.Y., Yip B.H.K., Osinga J., Hui K.J.W.S., Verheij J.B.G.M., Cherny S.S., Tam P.K.H., Sham P.C., Hofstra R.M.W. and Garcia-Barcelo M.M., Fine mapping of the 9q31 Hirschsprung's disease locus, Human Genetics. 2010, 127(6): 675-683.
Tang S.M., Tang W.K., So M.T., Miao X.P. and Leung M.C., Fine mapping of the NRG1 Hirschsprung’s disease locus, Human Molecular Genetics. 2010, Submitted.
Tang S.M., Garcia-Barcelo M.M., Cherny S.S., Sham P.C. and Tam P.K.H., Genome-wide profile of copy number variants for Hirschsprung's disease (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009.
Yip B.H.K., Ngan E.S.W., Garcia-Barcelo M.M., Cherny S.S., Tang S.M., Sham P.C. and Tam P.K.H., Quantifying epistasis between two sets of signaling pathway genes by canonical correlation analysis: with application on Hirschsprung's disease (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009.


Researcher : Tang SM
List of Research Outputs

Cherny S.S., Tang S.M., Sribudiani Y., Miao X., So M.T., Sham P.C., Tam P.K.H., Garcia-Barcelo M.M. and Hofstra R.M., Fine mapping of Hirschsprung's disease loci in 9q31 (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009.
Cornes B.K., Tang S.M., Leon Y.Y., Hui K.J.W.S., So M.T., Miao X., Cherny S.S., Sham P.C., Tam P.K.H. and Garcia-Barcelo M.M., Haplotype analysis reveals a possible founder effect of RET mutation R114H for Hirschsprung's disease in the Chinese population, PLoS One. 2010, 5 (6): e10918.
Garcia-Barcelo M.M., Yeung M.Y., Miao X.P., Tang S.M., Chen G., So M.T., Ngan E.S.W., Lui V.C.H., Chen Y., Liu X., Hui K.J.W.S., Li L., Guo W.H., Sun X.B., Tou J.F., Chan K.W., Wu X.Z., Song Y., Chan D., Cheung K.M.C., Chung P.H.Y., Wong K.K.Y., Sham P.C., Cherny S.S. and Tam P.K.H., Genome-wide association study identifies a susceptibility locus for biliary atresia on 10q24.2, Human Molecular Genetics. 2010, 19 (14): 2917-2925.
Garcia-Barcelo M.M., Tang W.Y., Miao X., Tang S.M., So M.T., Leon Y.Y., Sham P.C., Cherny S.S. and Tam P.K.H., Identification of rare variants in the NRG1 gene of Hirschsprung's patients (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009.
Sham P.C., Cornes B.K., Tang S.M., Leon Y.Y., So M.T., Tam P.K.H. and Garcia-Barcelo M.M., A RET founder mutation in Chinese Hirschsprung's patients (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009.
Tang S.M., Sribudiani Y., Miao X., de Vries A.R., Burzynski G., So M.T., Leon Y.Y., Yip B.H.K., Osinga J., Hui K.J.W.S., Verheij J.B.G.M., Cherny S.S., Tam P.K.H., Sham P.C., Hofstra R.M.W. and Garcia-Barcelo M.M., Fine mapping of the 9q31 Hirschsprung's disease locus, Human Genetics. 2010, 127(6): 675-683.
Tang S.M., Tang W.K., So M.T., Miao X.P. and Leung M.C., Fine mapping of the NRG1 Hirschsprung’s disease locus, Human Molecular Genetics. 2010, Submitted.
Tang S.M., Garcia-Barcelo M.M., Cherny S.S., Sham P.C. and Tam P.K.H., Genome-wide profile of copy number variants for Hirschsprung's disease (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009.
Yip B.H.K., Ngan E.S.W., Garcia-Barcelo M.M., Cherny S.S., Tang S.M., Sham P.C. and Tam P.K.H., Quantifying epistasis between two sets of signaling pathway genes by canonical correlation analysis: with application on Hirschsprung's disease (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009.


Researcher : Tang SW
List of Research Outputs

Wang H., Lau W.M., Yau S.Y., Li S.Y., Leung N., Wang N.L., Tang S.W., Lee T.M.C. and So K.F., Roles of paroxetine and corticosterone on adult mammalian ciliary body cell proliferation, Chinese Medical Journal. 2010, 123: 1305-1310.


Researcher : Tang YM
List of Research Outputs

Chan K.K.S., Hui C.L.M., Chiu C.P.Y., Lam M.L.M., Chan K.W., Lin J., Xu J., Tang Y.M., Wong G.H.Y., Longenecker J.M. and Chen E.Y.H., A 3-year prospective study of spontaneous eye-blink rate in first-episode schizophrenia: Relationships with neurocognitive functions and relapse, 2nd Schizophrenia International Research Society Conference (April 10-14, 2010), Florence, Italy. 2010.
Chan K.K.S., Wong G.H.Y., Hui C.L.M., Tang Y.M., Chan K.W., Lam M.L.M., Chiu C.P.Y. and Chen E.Y.H., Game Theoretical Approach to Theory of Mind Deficits in Schizophrenic Patients with Delusion(s) of Reference, Schizophrenia Research. 2010, 117 (2-3): 286.
Chan K.W., Chiu C.P.Y., Lam M.L.M., Hui C.L.M., Wong G.H.Y., Tang Y.M., Chan K.K.S. and Chen E.Y.H., Relationship of neurocognitive function and impairment of insight in first episode schizophrenia, Schizophrenia Research. 2010, 117 (2-3): 209.
Chang W.C., Tang Y.M., Chiu C.P.Y., Hui C.L.M., Lam M.L.M., Wong G.H.Y., Law C.W., Tso S., Chan K., Hung S.F., Chung D.W.S. and Chen E.Y.H., Gender differences in patients presented with first-episode psychosis in Hong Kong, Schizophrenia Research. 2010, 117 (2-3): 281-2.
Tang Y.M., Chiu C.P.Y., Hui C.L.M., Chan K.K.S., Lam M.L.M., Chan K.W., Wong G.H.Y. and Chen E.Y.H., Clinical and cognitive correlates of perceived extent of recovery in Chinese patients with psychosis, Schizophrenia Research. 2010, 117 (2-3): 516.
Tang Y.M., Wong G.H.Y., Hui C.L.M., Lam M.L.M., Chiu C.P.Y., Chan K.W., Chung D.W.S., Tso S., Chan K.P.M., Yip K.C., Hung S.F. and Chen E.Y.H., Early intervention for psychosis in Hong Kong - the EASY programme, Early Intervention in Psychiatry. 2010, 4 (3): 214-219.
Tang Y.M., Lam M.L.M., Wong H.Y., Hui C.L.M., Chiu C.P.Y., Law C.W., Chung D.W.S., Tso S., Yip K.C., Chen E.Y.H. and Hung S.F., Time to a stop or a change in prescription of initial antipsychotic medication in first-episode schizophrenic patients: A naturalistic study, 2nd Schizophrenia International Research Society Conference (April 10-14, 2010), Florence, Italy. 2010.
Wong G.H.Y., Tao H.J., He Z., Liu H.H., Chiu C.P.Y., Chan K.W., Lam M.L.M., Hui C.L.M., Tang Y.M., Wang Y.H., Xue Z.M., Liu Z.N. and Chen E.Y.H., Delusions of reference, excessive top-down processing, and default mode network in first-episode schizophrenia, Schizophrenia Research. 2010, 117 (2-3): 491.


Researcher : Tso KC
List of Research Outputs

Chung K.F., Tso K.C. and Chung R.T.Y., Validation of the Mood Disorder Questionnaire in the general population in Hong Kong, Comprehensive Psychiatry. 2009, 50 (5): 471-476.


Researcher : Wei R
List of Research Outputs

Deng Y., Meyer U., Lam S.S.Y., Feldon J., Li Q., Wei R., Luk L., Chua S.E., Sham P.C., Wang Y. and McAlonan G.M., Prenatal immune challenge causes frontal-subcortical proteome changes relevant to schizophrenia and autism, The International Journal of Neuropsychopharmacol. 2010.
Li Q., Cheung C., Wei R., Wong P., McAlonan G.M. and Wu E., Oral presentation: Prenatal immune challenge as a risk factor for white matter microstructural anomalies relevant to schizophrenia, The 15th Biennial Winter Workshop in Psychoses 2009, Barcelona, Espana (November 15-18, 2009). 2010.
Li Q., Cheung C., Cheung V., Zhang X., Wei R., Wong P., You Y.Q., Hui E., Chua S.E., McAlonan G.M. and Wu E.X., The timing of prenatal immune challenge determines the extent of postnatal white matter microstructural anomalies in a mouse model of schizophrenia, The International Journal of Neuropsychopharmacol. 2010.
Li Q., Cheung C., Wei R., Cheung V., Hui E.S., You Y., Wong P., Chua S.E., McAlonan G.M. and Wu E.X., Voxel-based analysis of postnatal white matter microstructure in mice exposed to immune challenge in early or late pregnancy, Neurolmage. 2010, 52(1): 1-8.
McAlonan G.M., Li Q., Cheung C., Wei R., Chua S.E., Sham P.C. and Wu E.X., Evidence that prenatal infection is a risk factor for brain and behaviour changes relevant to schizophrenia and autism, 41st European Brain and Behaviour Society Meeting (EBBS), Rhodes 2009. (September 13-18, 2009). 2010.
McAlonan G.M., Li Q., Cheung C., Wei R., Cheung V., Hui E.S.K., Wong P., Chua S.E. and Wu E.X., Oral presentation: The Timing of Prenatal Immune Challenge Determines the Extent of White Matter Microstructural Anomalies Relevant to Autism, International Meeting for Autism Research (IMFAR) Chicago 2010. (May 19-25, 2010). 2010.
McAlonan G.M., Cheung C., Li Q., Cheung V., Hui E.S.K., Wei R., Wong P., Chua S.E. and Wu E.X., The timing of prenatal immune challenge determines the extent of white matter microstructural anomalies relevant to schizophrenia, The 2nd Biennial Schizophrenia International Research Society Conference (SIRS), Florence, Italy, 2010. (April 9-16, 2010). 2010.
Wei R., Li Q., Chua S.E. and McAlonan G.M., Prenatal exposure to valproic acid induces a dose dependent impairment in sensorimotor gating in a mouse model of autism, The International Journal of Neuropsychopharmacol. 2010.
Wong N.K., Wong A.O.L., Lau N.K.C., Wei R., Zhang X., Li Q. and McAlonan G.M., Prenatal exposure of mice to a maternal immune challenge leads to changes in expression of genes regulating white matter, The International Journal of Neuropsychopharmacol. 2010.


Researcher : Wei R
List of Research Outputs

Deng Y., Meyer U., Lam S.S.Y., Feldon J., Li Q., Wei R., Luk L., Chua S.E., Sham P.C., Wang Y. and McAlonan G.M., Prenatal immune challenge causes frontal-subcortical proteome changes relevant to schizophrenia and autism, The International Journal of Neuropsychopharmacol. 2010.
Li Q., Cheung C., Wei R., Wong P., McAlonan G.M. and Wu E., Oral presentation: Prenatal immune challenge as a risk factor for white matter microstructural anomalies relevant to schizophrenia, The 15th Biennial Winter Workshop in Psychoses 2009, Barcelona, Espana (November 15-18, 2009). 2010.
Li Q., Cheung C., Cheung V., Zhang X., Wei R., Wong P., You Y.Q., Hui E., Chua S.E., McAlonan G.M. and Wu E.X., The timing of prenatal immune challenge determines the extent of postnatal white matter microstructural anomalies in a mouse model of schizophrenia, The International Journal of Neuropsychopharmacol. 2010.
Li Q., Cheung C., Wei R., Cheung V., Hui E.S., You Y., Wong P., Chua S.E., McAlonan G.M. and Wu E.X., Voxel-based analysis of postnatal white matter microstructure in mice exposed to immune challenge in early or late pregnancy, Neurolmage. 2010, 52(1): 1-8.
McAlonan G.M., Li Q., Cheung C., Wei R., Chua S.E., Sham P.C. and Wu E.X., Evidence that prenatal infection is a risk factor for brain and behaviour changes relevant to schizophrenia and autism, 41st European Brain and Behaviour Society Meeting (EBBS), Rhodes 2009. (September 13-18, 2009). 2010.
McAlonan G.M., Li Q., Cheung C., Wei R., Cheung V., Hui E.S.K., Wong P., Chua S.E. and Wu E.X., Oral presentation: The Timing of Prenatal Immune Challenge Determines the Extent of White Matter Microstructural Anomalies Relevant to Autism, International Meeting for Autism Research (IMFAR) Chicago 2010. (May 19-25, 2010). 2010.
McAlonan G.M., Cheung C., Li Q., Cheung V., Hui E.S.K., Wei R., Wong P., Chua S.E. and Wu E.X., The timing of prenatal immune challenge determines the extent of white matter microstructural anomalies relevant to schizophrenia, The 2nd Biennial Schizophrenia International Research Society Conference (SIRS), Florence, Italy, 2010. (April 9-16, 2010). 2010.
Wei R., Li Q., Chua S.E. and McAlonan G.M., Prenatal exposure to valproic acid induces a dose dependent impairment in sensorimotor gating in a mouse model of autism, The International Journal of Neuropsychopharmacol. 2010.
Wong N.K., Wong A.O.L., Lau N.K.C., Wei R., Zhang X., Li Q. and McAlonan G.M., Prenatal exposure of mice to a maternal immune challenge leads to changes in expression of genes regulating white matter, The International Journal of Neuropsychopharmacol. 2010.


Researcher : Wong GHY
List of Research Outputs

Chan K.K.S., Hui C.L.M., Chiu C.P.Y., Lam M.L.M., Chan K.W., Lin J., Xu J., Tang Y.M., Wong G.H.Y., Longenecker J.M. and Chen E.Y.H., A 3-year prospective study of spontaneous eye-blink rate in first-episode schizophrenia: Relationships with neurocognitive functions and relapse, 2nd Schizophrenia International Research Society Conference (April 10-14, 2010), Florence, Italy. 2010.
Chan K.K.S., Wong G.H.Y., Hui C.L.M., Tang Y.M., Chan K.W., Lam M.L.M., Chiu C.P.Y. and Chen E.Y.H., Game Theoretical Approach to Theory of Mind Deficits in Schizophrenic Patients with Delusion(s) of Reference, Schizophrenia Research. 2010, 117 (2-3): 286.
Chan K.W., Chiu C.P.Y., Lam M.L.M., Hui C.L.M., Wong G.H.Y., Tang Y.M., Chan K.K.S. and Chen E.Y.H., Relationship of neurocognitive function and impairment of insight in first episode schizophrenia, Schizophrenia Research. 2010, 117 (2-3): 209.
Chang W.C., Tang Y.M., Chiu C.P.Y., Hui C.L.M., Lam M.L.M., Wong G.H.Y., Law C.W., Tso S., Chan K., Hung S.F., Chung D.W.S. and Chen E.Y.H., Gender differences in patients presented with first-episode psychosis in Hong Kong, Schizophrenia Research. 2010, 117 (2-3): 281-2.
Tang Y.M., Chiu C.P.Y., Hui C.L.M., Chan K.K.S., Lam M.L.M., Chan K.W., Wong G.H.Y. and Chen E.Y.H., Clinical and cognitive correlates of perceived extent of recovery in Chinese patients with psychosis, Schizophrenia Research. 2010, 117 (2-3): 516.
Tang Y.M., Wong G.H.Y., Hui C.L.M., Lam M.L.M., Chiu C.P.Y., Chan K.W., Chung D.W.S., Tso S., Chan K.P.M., Yip K.C., Hung S.F. and Chen E.Y.H., Early intervention for psychosis in Hong Kong - the EASY programme, Early Intervention in Psychiatry. 2010, 4 (3): 214-219.
Wong G.H.Y., Tao H.J., He Z., Liu H.H., Chiu C.P.Y., Chan K.W., Lam M.L.M., Hui C.L.M., Tang Y.M., Wang Y.H., Xue Z.M., Liu Z.N. and Chen E.Y.H., Delusions of reference, excessive top-down processing, and default mode network in first-episode schizophrenia, Schizophrenia Research. 2010, 117 (2-3): 491.


Researcher : Wong HY
List of Research Outputs

Tang Y.M., Lam M.L.M., Wong H.Y., Hui C.L.M., Chiu C.P.Y., Law C.W., Chung D.W.S., Tso S., Yip K.C., Chen E.Y.H. and Hung S.F., Time to a stop or a change in prescription of initial antipsychotic medication in first-episode schizophrenic patients: A naturalistic study, 2nd Schizophrenia International Research Society Conference (April 10-14, 2010), Florence, Italy. 2010.


Researcher : Wong JGWS
Project Title:What makes a good clinical teacher in the new medical curriculum? A focus group study on student perception
Investigator(s):Wong JGWS, Lam TP, Mak-Lieh F
Department:Psychiatry
Source(s) of Funding:Other Funding Scheme
Start Date:01/2002
Abstract:
To examine medical student perceptions on what makes a good clinical teacher; to explore the concept of a good role model.


Project Title:A follow-up study on the severity of psychological sequelae in SARS patients
Investigator(s):Wong JGWS, Sham PC, Wong PC, McAlonan GM, Chu CM, Lee AM, Lee PWH, Tsang KWT, Chua SE
Department:Psychiatry
Source(s) of Funding:Small Project Funding
Start Date:11/2004
Abstract:
To assess severity of psychological sequelae in SARS patients (including infected HCWS after recovery from the infection; to assess severity of psychological sequelae in high risk and low risk HCWs after the SARS outbreak; to inform psychological intervention in the event of a future outbreak.




Researcher : Wong MMC
Project Title:Enrichment of collections in the library of the S.K. Yee Mental Health Resources and Rehabilitation Centre
Investigator(s):Wong MMC, Mak KY, Mak-Lieh F, Yau EFY
Department:Psychiatry
Source(s) of Funding:S.K. Yee Medical Foundation - General Award
Start Date:10/2001
Abstract:
Taking care of mentally people in the community is often a great stress to the caregivers (including family members and staff of those agencies which are involved in the rehabilitation of the patients in the community). They often lack the knowledge in mental illness and are not equipped with the skills in taking care of the mentally ill patients. Therefore apart from offering services to the patients, the service should be extended to cover the caregivers. They should have easy access to information (including written and audio-visual material) so that they can have better knowledge on mental illness and can learn the skills in taking care of the mentally ill patients. It is also important to help the public to change their attitude towards the mentally ill through various public education materials which improve their awardness, understanding and acceptance of mental illness in the community.


List of Research Outputs

Mak K.Y., Wong M.M.C., Han S.H. and Lee T.M.C., Gray matter reduction associated with emotion regulation in female outpatients with major depressive disorder: A voxel-based morphometry study, Progress in Neuropsychopharmacology and Biological Psychiatry. 2009, 33: 1184-1190.


Researcher : Wong NK
List of Research Outputs

Wong N.K., Wong A.O.L., Lau N.K.C., Wei R., Zhang X., Li Q. and McAlonan G.M., Prenatal exposure of mice to a maternal immune challenge leads to changes in expression of genes regulating white matter, The International Journal of Neuropsychopharmacol. 2010.


Researcher : Wong TKW
List of Research Outputs

Cheung C., Chua S.E., Cheung V., Khong P.L., Tai K.S., Wong T.K.W., Ho T.P. and McAlonan G.M., White matter fractional anisotrophy differences and correlates of diagnostic symptoms in autism, Journal of Child Psychology and Psychiatry. 2009, 50: 1102-1112.


Researcher : Wuwongse S
List of Research Outputs

Chang R.C.C., Zhang Q., Hung H.L., Cheung Y.T., Ho Y.S., Lai S.W. and Wuwongse S., Pathogenesis of Alzheimer's Disease, 5th International Symposium on Healthy Aging. 2010, Page 19.
Wuwongse S., Hung H.L., Law A.C.K. and Chang R.C.C., Corticosterone induced synaptic degeneration in depression and Alzheimer's disease, Collegium Internationale Neuro-Psychopharmacologicum (CINP) 2010 World Congress. 2010, P-09.
Wuwongse S., Chang R.C.C. and Law A.C.K., Exploriing the Connection between Depression and Dementia, HKU 14th Research Postgraduate Symposium, Hong Kong (December 2-3, 2009). 2010.
Wuwongse S., Law A.C.K. and Chang R.C.C., Investigating synaptic degeneration as common pathophysiological factor in depression and Alzheimer's disease, 11th International Geneva/Springfield Symposium on Advances in Alzheimer Therapy, March 24-27, 2010 Geneva. 2010, 87.
Wuwongse S., Chang R.C.C. and Law A.C.K., Investigation of synaptic degeneration in depression and Alzheimer's disease, 5th International Symposium on Healthy Aging. 2010, Page 52.
Wuwongse S., Chang R.C.C. and Law A.C.K., The potential effects of antidepressants in attenuating synaptic degeneration in depression and Alzheimer's disease, 18th European Congress of Psychiatry, Munich, Germany (February 28 - March 2, 2010). 2010.


Researcher : Wuwongse S
List of Research Outputs

Chang R.C.C., Zhang Q., Hung H.L., Cheung Y.T., Ho Y.S., Lai S.W. and Wuwongse S., Pathogenesis of Alzheimer's Disease, 5th International Symposium on Healthy Aging. 2010, Page 19.
Wuwongse S., Hung H.L., Law A.C.K. and Chang R.C.C., Corticosterone induced synaptic degeneration in depression and Alzheimer's disease, Collegium Internationale Neuro-Psychopharmacologicum (CINP) 2010 World Congress. 2010, P-09.
Wuwongse S., Chang R.C.C. and Law A.C.K., Exploriing the Connection between Depression and Dementia, HKU 14th Research Postgraduate Symposium, Hong Kong (December 2-3, 2009). 2010.
Wuwongse S., Law A.C.K. and Chang R.C.C., Investigating synaptic degeneration as common pathophysiological factor in depression and Alzheimer's disease, 11th International Geneva/Springfield Symposium on Advances in Alzheimer Therapy, March 24-27, 2010 Geneva. 2010, 87.
Wuwongse S., Chang R.C.C. and Law A.C.K., Investigation of synaptic degeneration in depression and Alzheimer's disease, 5th International Symposium on Healthy Aging. 2010, Page 52.
Wuwongse S., Chang R.C.C. and Law A.C.K., The potential effects of antidepressants in attenuating synaptic degeneration in depression and Alzheimer's disease, 18th European Congress of Psychiatry, Munich, Germany (February 28 - March 2, 2010). 2010.


Researcher : Xu J
List of Research Outputs

Chan K.K.S., Hui C.L.M., Chiu C.P.Y., Lam M.L.M., Chan K.W., Lin J., Xu J., Tang Y.M., Wong G.H.Y., Longenecker J.M. and Chen E.Y.H., A 3-year prospective study of spontaneous eye-blink rate in first-episode schizophrenia: Relationships with neurocognitive functions and relapse, 2nd Schizophrenia International Research Society Conference (April 10-14, 2010), Florence, Italy. 2010.


Researcher : Yao N
List of Research Outputs

Cheung C., Yee Y.F., Fung G.C.M., Yu K.K.K., Yao N., You Y., McAlonan G.M. and Chua S.E., MRI brain scan study of minor physical anomalies to aid the early diagnosis of autism, International College of Neuropsychopharmacology 2010, Hong Kong (June 6-10, 2010). 2010.


Researcher : Yeung MY
List of Research Outputs

Garcia-Barcelo M.M., Yeung M.Y., Miao X.P., Tang S.M., Chen G., So M.T., Ngan E.S.W., Lui V.C.H., Chen Y., Liu X., Hui K.J.W.S., Li L., Guo W.H., Sun X.B., Tou J.F., Chan K.W., Wu X.Z., Song Y., Chan D., Cheung K.M.C., Chung P.H.Y., Wong K.K.Y., Sham P.C., Cherny S.S. and Tam P.K.H., Genome-wide association study identifies a susceptibility locus for biliary atresia on 10q24.2, Human Molecular Genetics. 2010, 19 (14): 2917-2925.


Researcher : Yeung WF
List of Research Outputs

Yeung W.F., Chung K.F. and Zhang S.P., A randomized controlled trial of electroacupuncture for residual insomnia associated with major depressive disorder, T.W.G.H.S. Eddie Wang Chinese Medicine Postgraduate Forum, Hong Kong: Tung Wah Group of Hospitals and Hospital Authority, 2010.
Yeung W.F., Chung K.F. and Zhang S.P., Acupuncture for residual insomnia Associated with Major Depressive Disorder: A Randomized Placebo-Controlled Trial, 2009 Hong Kong - Macau Postgraduate Symposium on Chinese Medicine. Hong Kong: Modernized Chinese Medicine International Association, August 13, 2009.
Yeung W.F., Best Paper Award – Champion, TWGHS Eddie Wang Chinese Medicine Postgraduate Forum 2010, T.W.G.H.S. and Hospital Authority. 2010.
Yeung W.F., Champion of Preliminary Round (Hong Kong & Macau), TWGHS Eddie Wang Chinese Medicine Postgraduate Forum 2010 , T.W.G.H.S. and Hospital Authority. 2010.
Yeung W.F., Chung K.F., Zhang S.P., Yap T.G. and Law A.C.K., Electroacupuncture for Primary Insomnia: A Randomized Controlled Trial, Sleep. 2009, 32 (8): 1039-1047.
Yeung W.F., Chung K.F. and Wong C.Y., Relationship between insomnia and headache in community-based middle-aged Hong kong Chinese women, J Headache Pain. 2010, 11: 187-195.


Researcher : Yip BHK
Project Title:Sequencing of the neuregulin-1 (NRG1) gene in schizophrenia patients
Investigator(s):Yip BHK, Sham PC, Cherny SS, Garcia-Barcelo MM, Tam PKH
Department:Psychiatry
Source(s) of Funding:Small Project Funding
Start Date:08/2009
Abstract:
Neuregulin-1 (NRG1), is one of the best-supported schizophrenia (SZ) susceptibility genes (1), although how genetic variation impacts on the disease remains uncertain. The first report on the association of NRG1 with SZ described a “core-risk haplotype” at the 5’ end of the gene in the Icelandic population (Icelandic haplotype) (2). Follow-up studies confirmed the association of NRG1 with SZ in different populations (3,4). However, while studies conducted on Asians reported the association not only with the “Icelandic haplotype” but also with markers at the 3’ end of the gene (5,6), studies conducted on Hispanics (Central Valley of Costa Rica population; CVCR) revealed the association SZ with a NRG1 haplotype distinct from the Icelandic or the 3’ markers associated with SZ in Chinese (7). Sequencing of NRG1 in CVCR SZ and chronic psychosis families revealed the presence of the V266L missense mutation and family-based association tests demonstrated its association with those conditions (8). V266L was also identified in patients of different ancestry, including Western, Eastern and Northern European. Intriguingly, V266L was reported not to be in complete linkage disequilibrium (LD) with the Icelandic haplotype nor with the NRG1 haplotype associated with SZ in CVCRs. This suggested the presence of an additional independent SZ susceptibility locus within NRG1. The V266L residue of the NRG1 protein has been conserved throughout evolution and its replacement is predicted to be damaging. Given the relevance of this finding, we aim to investigate the presence of this mutation in the Chinese population. We plan to sequence exon 12 of NRG1, where V226L resides, of 270 Chinese SZ patients and 270 matched controls. REFERENCE 1. Mei L, Xiong WC. (2008): Neuregulin 1 in neural development, synaptic plasticity and schizophrenia. Nat Rev Neurosci 9:437-452. 2. Stefansson H and others. (2002): Neuregulin 1 and susceptibility to schizophrenia. Am J Hum Genet 71:877-892. 3. Stefansson H and others. (2003): Association of neuregulin 1 with schizophrenia confirmed in a Scottish population. Am J Hum Genet 72:83-87. 4. Williams NM and others. (2003): Support for genetic variation in neuregulin 1 and susceptibility to schizophrenia. Mol Psychiatry 8:485-487. 5. Li T and others. (2004): Identification of a novel neuregulin 1 at-risk haplotype in Han schizophrenia Chinese patients, but no association with the Icelandic/Scottish risk haplotype. Mol Psychiatry 9:698-704. 6. Yang JZ and others. (2003): Association study of neuregulin 1 gene with schizophrenia. Mol Psychiatry 8:706-709 7. Walss-Bass C and others. (9-15-2006): A novel missense mutation in the transmembrane domain of neuregulin 1 is associated with schizophrenia. Biol Psychiatry 60:548-553. 8. Walss-Bass C and others. (2006): Association analyses of the neuregulin 1 gene with schizophrenia and manic psychosis in a Hispanic population. Acta Psychiatr Scand 113:314-321.


Project Title:59th Annual Meeting of the American Society of Human Genetics Quantifying epistasis between two sets of signaling pathway genes by canonical correlation analysis.
Investigator(s):Yip BHK
Department:Psychiatry
Source(s) of Funding:URC/CRCG - Conference Grants for Teaching Staff
Start Date:10/2009
Completion Date:10/2009
Abstract:
N/A


List of Research Outputs

Leung M.K., Cheung C., Yu K.K.K., Yip B.H.K., Sham P.C., Li Q., Chua S.E. and McAlonan G.M., Gray Matter in First-Episode Schizophrenia Before and After Antipsychotic Drug Treatment. Anatomical Likelihood Estimation Meta-analyses With Sample Size Weighting, Schizophrenia Bulletin . 2009, 16.
Ngan E.S.W., Garcia-Barcelo M.M., Yip B.H.K., Sham P.C., Lui V.C.H. and Tam P.K.H., Hedgehog-notch induced premature gliogenesis of neural crest: a cause of Hirschsprung disease, International Society for Stem Cell Research, the 8th Annual Meeting, Moscone West, San Francisco, U.S.A. 16-19 June 2010.
Tang S.M., Sribudiani Y., Miao X., de Vries A.R., Burzynski G., So M.T., Leon Y.Y., Yip B.H.K., Osinga J., Hui K.J.W.S., Verheij J.B.G.M., Cherny S.S., Tam P.K.H., Sham P.C., Hofstra R.M.W. and Garcia-Barcelo M.M., Fine mapping of the 9q31 Hirschsprung's disease locus, Human Genetics. 2010, 127(6): 675-683.
Yip B.H.K., Ngan E.S.W., Garcia-Barcelo M.M., Cherny S.S., Tang S.M., Sham P.C. and Tam P.K.H., Quantifying epistasis between two sets of signaling pathway genes by canonical correlation analysis: with application on Hirschsprung's disease (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009.


Researcher : Yu GKK
List of Research Outputs

Chu L.W., Chan I., Lee P.W.H., Li S.W. and Yu G.K.K., Effects of cognitive function and depressive mood on the quality of life in Chinese Alzheimer's disease patients in Hong Hong, Geriatrics and Gerontology International. 2010, 1-8.


Researcher : Yu KKK
List of Research Outputs

Cheung C., Yee Y.F., Fung G.C.M., Yu K.K.K., Yao N., You Y., McAlonan G.M. and Chua S.E., MRI brain scan study of minor physical anomalies to aid the early diagnosis of autism, International College of Neuropsychopharmacology 2010, Hong Kong (June 6-10, 2010). 2010.
Leung M.K., Cheung C., Yu K.K.K., Yip B.H.K., Sham P.C., Li Q., Chua S.E. and McAlonan G.M., Gray Matter in First-Episode Schizophrenia Before and After Antipsychotic Drug Treatment. Anatomical Likelihood Estimation Meta-analyses With Sample Size Weighting, Schizophrenia Bulletin . 2009, 16.


Researcher : Yu KKK
List of Research Outputs

Cheung C., Yee Y.F., Fung G.C.M., Yu K.K.K., Yao N., You Y., McAlonan G.M. and Chua S.E., MRI brain scan study of minor physical anomalies to aid the early diagnosis of autism, International College of Neuropsychopharmacology 2010, Hong Kong (June 6-10, 2010). 2010.
Leung M.K., Cheung C., Yu K.K.K., Yip B.H.K., Sham P.C., Li Q., Chua S.E. and McAlonan G.M., Gray Matter in First-Episode Schizophrenia Before and After Antipsychotic Drug Treatment. Anatomical Likelihood Estimation Meta-analyses With Sample Size Weighting, Schizophrenia Bulletin . 2009, 16.


Researcher : Zhang SP
List of Research Outputs

Yeung W.F., Chung K.F. and Zhang S.P., A randomized controlled trial of electroacupuncture for residual insomnia associated with major depressive disorder, T.W.G.H.S. Eddie Wang Chinese Medicine Postgraduate Forum, Hong Kong: Tung Wah Group of Hospitals and Hospital Authority, 2010.
Yeung W.F., Chung K.F. and Zhang S.P., Acupuncture for residual insomnia Associated with Major Depressive Disorder: A Randomized Placebo-Controlled Trial, 2009 Hong Kong - Macau Postgraduate Symposium on Chinese Medicine. Hong Kong: Modernized Chinese Medicine International Association, August 13, 2009.
Yeung W.F., Chung K.F., Zhang S.P., Yap T.G. and Law A.C.K., Electroacupuncture for Primary Insomnia: A Randomized Controlled Trial, Sleep. 2009, 32 (8): 1039-1047.


Researcher : Zhang X
List of Research Outputs

Li Q., Cheung C., Cheung V., Zhang X., Wei R., Wong P., You Y.Q., Hui E., Chua S.E., McAlonan G.M. and Wu E.X., The timing of prenatal immune challenge determines the extent of postnatal white matter microstructural anomalies in a mouse model of schizophrenia, The International Journal of Neuropsychopharmacol. 2010.
Wong N.K., Wong A.O.L., Lau N.K.C., Wei R., Zhang X., Li Q. and McAlonan G.M., Prenatal exposure of mice to a maternal immune challenge leads to changes in expression of genes regulating white matter, The International Journal of Neuropsychopharmacol. 2010.


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