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Dr Chang joined the Department of Psychiatry at the University of Hong Kong in January 2011. His clinical and research interests focus on early schizophrenia and related psychotic disorders. He is currently a clinical assistant professor at the Department and an honorary associate consultant of the EASY clinical team (early intervention for psychosis) at Queen Mary Hospital.
Long-term outcome of first-episode psychosis
Schizophrenia and related psychoses are severe mental illnesses causing enormous burden to patients, their families and society. At present, the majority of outcome studies on psychotic disorders are based on samples of chronic illness. There is a need to study the illness trajectory right from the onset of psychosis to further clarify and delineate the factors determining the long-term prognosis. We have conducted a number of prospective first-episode psychosis cohort studies to address these important yet unanswered questions. Our previous research (FEP3 and FEP12 study) revealed that prolonged duration of untreated psychosis (DUP) predicted both short-term (3-year) (Chang et al. Psy Med. 2013) and long-term (12-year) clinical outcome of the disorder. Cognitive impairment, in particular verbal memory function was found to predict symptom remission at follow-up (Chang et al. J Clin Psychiatry 2013). Achievement of early symptom remission status was shown to predict longer-term psychosocial functioning (Chang et al. Sch Res. 2013), thereby also indicating the predictive validity of recently consensus-derived operational symptom remission criteria for schizophrenia. Additionally, prospective investigations of occupational outcome predictors, relationship between negative symptoms and cognitive functioning, relapse and suicide risk prediction, sex difference and impact of premorbid adjustment on illness outcomes etc. were conducted. We are also carrying out another long-term follow-up study (8 years) in a group of remitted first-episode psychosis patients to examine the effects of early treatment discontinuation on outcomes of clinical, functional and cognitive domains.
Current research project: FEP12 study, RPS8 study, HOPE study
Longitudinal study on evolution of negative symptoms in first-episode psychosis
Negative symptoms are a core feature of schizophrenia and related psychoses. Despite advance in pharmacological interventions, negative symptoms still represent an unmet therapeutic need and are associated with poor functional outcome and limited response to medication treatment. Given its clinical significance alongside the fact of a paucity of data regarding the evolution and trajectory of negative symptoms in the early illness course, we have conducted a 3-year prospective follow-up study on patients with first-episode schizophrenia and systematically investigated the development of negative symptom and its clinical and cognitive correlates. Our results showed that approximately one-fourths of first-episode patients developed persistent negative symptoms over 3 years after treatment initiation (Chang et al. Sch Res. 2011). Our study indicated that prolonged treatment delay (duration of untreated psychosis) and poor premorbid adjustment were associated with negative symptom severity and development of persistent negative symptoms (Chang et al. Sch Res. 2011; Psy Med. 2013). Our findings thus extend the literature with regard to identification of illness factors predictive of persistent negative symptoms and highlight the importance of early detection and delivery of intensive interventions to address these potentially debilitating symptoms. Our ongoing research will further clarify the long-term development of negative symptoms and the related cognitive and functional outcomes.
Current research project: HOPE study, RPS8 study, FEP12 study
Reward learning impairment in early psychosis
Reward learning has been regarded as a promising paradigm for translational research in schizophrenia and related psychoses. Reward processing is closely associated with dopamine, which is a key neurotransmitter dysregulated in psychosis, and the primary target of current drug treatment. Brain systems involved in reward processing are implicated in psychosis development. Reward system also provides a useful theoretical framework linking symptom manifestations to neurobiological dysfunction underlying psychosis. Literature indicated that chronic schizophrenia patients had reward learning impairment. Nonetheless, such impairment in the early stage of psychotic illness, within which confounding effects of antipsychotic exposure and illness duration on reward learning could be minimized, has been under-studied. Further, reward learning may be a useful candidate in psychosis prediction from at-risk mental state. Our research team conducts prospective follow-up study in both first-episode psychosis and at-risk mental state samples to examine the presence and degree of reward learning deficit, and its relationship with symptom and cognitive functions.
Current research project: Reward learning study in first-episode psychosis
Evaluation of early interventions for first-episode psychosis
In the past two decades, early intervention programs for psychosis have been established worldwide. Hong Kong is among the first few cities in Asia implementing such early intervention service (namely EASY or Early Assessment Service for Young people with psychosis). Although both overseas and local findings indicated that early intervention is effective in symptom and functional improvement when compared to standard psychiatric care, recent data suggested that these initial therapeutic benefits could not be sustained after withdrawal of 2-year early intervention service. Thus far, there is no data available with regard to an optimal length and durability of early intervention. Our research team has just completed a randomized controlled trial (RCT) comparing extended 1-year specialized early intervention in the form of community-based case management with standard step-down care in a cohort of patients who had been treated in the 2-year EASY program for their first-episode psychosis. This is the first RCT addressing the effectiveness of service-level early intervention with its treatment duration beyond usual 2-year period. Our results supported an implementation of longer-term early intervention which was superior to standard care in functional improvement, reduction of negative and depressive symptoms, and lowering of treatment default rate. We are currently conducting a 2-year follow-up study of this patient cohort to address an as yet unanswered question of whether the positive treatment effects of extended early intervention could be sustained over a longer period of time, and hence an optimal period of early intervention for psychotic disorders. Another large-scale RCT focusing on 4-year versus 2-year early intervention in adult-onset first-episode psychosis, namely JCEP project is also underway. Additionally, we are also interested in studying psychosocial interventions that address functional enhancement of early psychosis patients who otherwise exhibit significant impairment in social functioning even in the presence of clinical remission.
Current research project: EASY5 study, Life coaching intervention RCT, JCEP project
At-risk mental state research on prediction of conversion to psychotic disorders
Early intervention for psychosis has been the major focus in mental health care development worldwide in the past decade with particular emphasis on using operationalized clinical criteria in identifying individuals at high-risk for psychosis. It is suggested that intervention in this pre-psychotic period may prevent progression to full-blown psychosis. Nonetheless, thus far, no robust predictors of psychosis transition have been identified and sensitivity of these clinical criteria remained low. Our prior study revealed a relatively high transition rate of at-risk mental state to psychosis (45% in 2 years). Currently, we participate in a multi-site collaboration randomized controlled trial, Neurapro-E study which evaluates the effectiveness of omega-3 fatty acids combined with cognitive-behavioural case management on preventing conversion from at-risk mental state to psychotic disorders. In order to further clarify the clinical profiles of at-risk mental state and to enhance prediction model for psychosis transition, we will conduct studies in this clinical high-risk sample using reward learning paradigm to examine whether this cognitive approach in combination with clinical criteria will further enhance prediction for psychosis development.
Current research project: NEURAPRO-E study, Reward learning study in at-risk mental state
Diagnostic concepts and instability of early psychosis
Diagnosis is regarded as a sine qua non for clinical practice and research. Currently, owing to unknown underlying aetiopathophysiology and lack of objective indicators for definitive diagnostic ascertainment, diagnoses of psychotic disorders defined by contemporary taxonomies still rely on explicit operational criteria on the basis of phenomenological approach, i.e. symptoms recognition. Our earlier study demonstrated diagnostic instability in those less frequent diagnostic entities including acute and transient psychotic disorders and unspecified non-organic psychosis in the initial 5 years of illness. Schizoaffective disorder is also repeatedly shown to be diagnostically unstable. Given the introduction of new diagnostic scheme in DSM-V with modification of criteria for some diagnostic categories and the upcoming ICD-11, there is a need to re-examine the issue of diagnostic change, particularly in the early course of illness within which the symptom manifestation is fluid and relatively less specific when compared to the more typical presentation associated with the diagnostic prototypes of schizophrenia and bipolar disorder.
Current research project: HOPE study on delusional disorder, acute psychosis and schizoaffective disorder
Investigation of socio-environmental factors determining the cause & outcome of psychotic disorders
Substantial evidence suggests that socio-environmental factors play a critical role in psychosis development. In particular, migration is one of the most studied putative social determinants for psychosis with literature consistently showing that migrant status was associated with heightened risk for psychosis. However, most of these studies were generated in western populations with those migrants being ethnic minority. Our preliminary findings based on JCEP project suggested that Mainland Chinese immigrants may harbour an elevated risk for psychosis development when compared to the locally-born Hong Kong Chinese. Given that Mainland Chinese immigrants constitute the fastest-growing population group in Hong Kong in the recent decade and the forthcoming years, an increased rate of psychosis in this migrant group may significantly impact upon current mental health and social welfare systems. More research is required to clarify this issue and its potential underlying mechanism.
Current research project: JCEP project
Epidemiological investigation of prevalence of psychotic disorders in Hong Kong
Epidemiological investigation of psychotic disorders is of great importance. HKMMS is the first epidemiological study in Hong Kong which examines the prevalence of several major mental disorders including psychotic disorders, depression and anxiety disorders. This study evaluates 5700 subjects randomly selected from the general population. The findings will inform service developers and policy makers in mental health care service development to address the treatment needs. The local epidemiological landscape of psychosis will also be clarified.
Current research project: HKMMS