Hm Lee

Negative symptom dimensions differentially impact on functioning in individuals at-risk for psychosis

a Department of Psychiatry, The University of Hong Kong, Queen Mary Hospital, Hong Kong b State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong c Department of Psychiatry, Queen Mary Hospital, Hong Kong d Department of Psychiatry, Pamela Youde Nethersole Eastern Hospital, Hong Kong e Department of Psychiatry, Kwai Chung Hospital, Hong Kong f Department of Psychiatry, Kowloon Hospital, Hong Kong g Department of Psychiatry, United Christian Hospital, Hong Kong h Department of Psychiatry, Tai Po Hospital, Hong Kong i Department of Psychiatry, Alice Ho Miu Ling Nethersole Hospital, Hong Kong j Department of Psychiatry, Castle Peak Hospital, Hong Kong

T250. CLINICAL CORRELATES OF SUBJECTIVE QUALITY OF LIFE IN INDIVIDUALS WITH AT-RISK MENTAL STATE FOR PSYCHOSIS IN HONG KONG

Abstract Background Subjective quality of life (SQoL) is an important outcome domain in individuals with at-risk mental state (ARMS) for psychosis. In an effort to better understand and maximize SQoL in ARMS populations, an increasing number of research has been conducted to investigate factors determining SQoL. This study aimed to examine clinical, functional and cognitive correlates of SQoL in Chinese young people presenting with ARMS in Hong Kong. Methods This is a naturalistic prospective study examining the longitudinal course of ARMS and prediction of psychosis in Hong Kong. In total, 110 Chinese participants aged 15 to 40 years presenting with ARMS were recruited from a territory-wide specialized early intervention service for psychosis. ARMS status was verified using Comprehensive Assessment for At-Risk Mental State (CAARMS). Assessments encompassing symptom profiles (Positive and Negative Syndrome Scale, PANSS; Montgomery-Asberg Depression Rating Scale, MADRS; Brief Negative Symptom Scale, BNSS), functioning (Social and Occupational Functioning Rating Scale, SOFAS) and a brief battery of cognitive tests was conducted. A validated Chinese version of SF12 questionnaire was used to measure SQoL. The current analysis focused on data collected at baseline. Results Of 110 ARMS participants, 48.2% were male. The mean age and educational level of the sample was 20.9 years (S.D.=6.7) and 11.4 years (S.D.=2.6), respectively. Correlation analyses revealed that SF12 mental health score was correlated with MADRS total score, BNSS total score and SOFAS score, while SF12 physical health score was correlated with PANSS positive symptom score only (p<0.05). Multiple linear regression analysis showed that only MADRS total score was independently associated with SF12 mental health score (p<0.001). SQoL measures were not correlated with any cognitive functions. Discussion Our results were consistent with the literature which indicates that psychological domain of SQoL is significantly related to depressive symptoms in ARMS individuals. Further analysis on the longitudinal data regarding our prospective ARMS cohort will clarify variables predictive of SQoL at follow-up.

T62. COMPARISON OF NEUROCOGNITIVE FUNCTIONS IN FIRST-EPISODE SCHIZOPHRENIA PATIENTS, NON-PSYCHOTIC SIBLINGS, AND INDIVIDUALS AT CLINICAL HIGH-RISK FOR PSYCHOSIS

Abstract Background Neurocognitive impairment is a core feature of schizophrenia, and has been observed among healthy non-psychotic siblings of schizophrenia patients as well as individuals at clinical high-risk (CHR) for psychosis. Thus far, few studies have directly contrasted neurocognitive performance between non-psychotic siblings and CHR samples. Potential differential patterns of neurocognitive deficits among schizophrenia patients, familial high-risk and CHR samples remain to be clarified. This study aimed to compare neurocognitive functions among first-episode schizophrenia (FES) patients, their non-psychotic siblings, CHR individuals, and healthy controls. Methods FES patients (n=69, mean age=25.3) and CHR individuals (n=97, mean age=21.1) without family history of psychosis were recruited from a territory-wide specialized early intervention service for psychosis in Hong Kong. A group of non-psychotic siblings of FES patients (n=50, mean age=25.4) and healthy controls (HC) (n=68, mean age=24.5) were also recruited. A standardized battery of neurocognitive tests encompassing working memory, processing speed, executive function, visual memory, verbal learning, and sustained attention was administered. Group differences were examined using analysis of covariance (ACOVA) with Bonferroni correction applied for statistical significance (P<0.008), controlling for age and years of education. Results Compared with HC, FES patients exhibited significantly poorer performance across all neurocognitive domains (Hedges g ranged: 0.48–1.73), while CHR individuals demonstrated significantly worse neurocognitive functioning in all domains (Hedges g ranged: 0.53–1.15) but sustained attention. Non-psychotic performed significantly worse than HC in executive function (Hedges g=0.63, p<0.001), visual memory (Hedges g=0.57, p=0.002), verbal learning (Hedges g=0.52, p=0.001), and working memory (Hedges g=0.37, p=0.003). Among four groups, FES patients displayed the most severe neurocognitive impairment. The pattern of neurocognitive dysfunction was similar between CHR and non-psychotic sibling groups, except for processing speed, of which CHR individuals demonstrated greater degree of impairment than siblings in digit symbol coding test (p<0.001). Discussion Our results indicate a gradient of neurocognitive impairment across FES, CHR and non-psychotic sibling samples, reflecting differential degrees of psychosis liability. Processing speed, as measured by digit symbol coding test, demonstrated the highest discriminant utility in discriminating CHR from familial high-risk individuals. Our findings thus confirm the critical role of neurocognitive dysfunction as a reliable risk indicator and an endophenotype for schizophrenia and related psychoses.

S122. 3-YEAR NEGATIVE SYMPTOM TRAJECTORY AND ITS RELATIONSHIP WITH SYMPTOM AND FUNCTIONAL OUTCOMES IN FIRST-EPISODE NON-AFFECTIVE PSYCHOSIS: A PROSPECTIVE 13-YEAR FOLLOW-UP STUDY

Abstract Background Negative symptoms are a core feature of schizophrenia and are a major determinant of functional impairment. Few studies have been conducted to examine patterns of longitudinal course of negative symptoms in the early stage of illness. Differential relationships of negative symptom trajectories with long-term clinical and functional outcomes remain to be clarified. This study aimed to investigate patterns of negative symptom trajectories over 3 years, utilizing latent class growth analysis (LCGA), in patients presenting with first-episode non-affective psychosis. Predictive capacity of symptom trajectories on 13-year functional and negative symptom outcomes was also examined. Methods One hundred thirty-six Chinese patients aged 18–55 years presenting with DSM-IV first-episode schizophrenia, schizoaffective disorder, schizophreniform disorder, brief psychotic disorder or delusional disorder were assessed at clinical stabilization for first psychotic episode (baseline), 1, 2, 3 and 13 years of follow-up. Assessments encompassing premorbid adjustment, baseline symptom and cognitive profiles and functional levels were conducted. Negative symptoms were measured by High Royds Evaluation of Negativity (HEN) Scale. Individual class membership of negative symptoms derived from LCGA was based on HEN ratings at baseline, 1, 2 and 3-year follow-up. Results Three distinct negative symptom trajectories were identified including low-stable (59.6%, n=81), moderate-stable (29.4%, n=40) and high-increasing (11.0%, n=15) trajectories. Multinomial regression analysis revealed that poorer premorbid adjustment, lower baseline cognitive composite scores and more severe baseline depression predicted high-increasing trajectory membership (Nagelkerke pseudo R2=0.339, Model χ2=277.96, p<0.01). At 13 years, 88 patients (64.7%) completed follow-up assessment, with attrition analysis indicating lack of significant differences in demographic, premorbid and baseline characteristics between completers and non-completers. Analysis of covariance (controlling for premorbid adjustment, baseline cognition and depression) followed by post-hoc comparison analyses found that high-increasing trajectory was significantly associated with poorer global functional outcome and higher negative symptom levels at 13-year follow-up. Discussion Our results indicate that 11% of first-episode non-affective psychosis patients displayed persistently high levels of negative symptoms with gradual symptom worsening over 3-year follow-up. This trajectory membership was predictive of poorer negative symptom and functional outcomes 13 years after presentation. High-increasing negative symptom trajectory identified in the initial 3 years of treatment for first-episode psychosis may represent a subgroup of patients having markedly elevated risk of developing deficit syndrome in the later course of illness.

T252. TREATMENT DELAY AND OUTCOME COMPARISON OF EXTENDED EARLY INTERVENTION SERVICE AND STANDARD PSYCHIATRIC CARE FOR ADULTS PRESENTING WITH FIRST-EPISODE PSYCHOSIS IN HONG KONG

Abstract Background A territory-wide specialized early intervention (EI) service for psychosis (EASY) has been implemented in Hong Kong since 2001, providing 2-year phase-specific early assessment and clinical care to young people aged 15–25 years presenting with first-episode psychosis (FEP). Previous evaluation demonstrated superiority of EASY programme over standard care in outcome improvement in FEP. Recently, EASY has been extended to provide 3-year EI service to FEP patients aged 15 to 64 years. However, effectiveness of EI on adult FEP populations has not been well examined. Methods This study adopted case versus historical-control design, comparing patients received 3-year EASY treatment (EI group) with those managed by standard psychiatric care (SC group) prior to implementation of EASY extension in terms of treatment delay and outcomes in symptom and functioning. In total, 320 Chinese adult FEP patients aged 26–55 years (160 in EI group, 160 in SC group) were included in the study. Retrospective record review detailing service utilization over 3-year treatment period was conducted. Follow-up interview assessment (on average 48.3 months after service entry) encompassing premorbid adjustment, duration of untreated psychosis (DUP), clinical (Positive and Negative Syndrome Scale, PANSS; Calgary Depression Scale, CDS), functional (Role Functioning Scale, RFS) and treatment profiles was administered. Comparison analyses on DUP and service utilization were based on record review data of 320 patients. Clinical and functional outcome analyses focused on data collected from follow-up interview assessment (251 patients completed follow-up assessment, 130 from EI and 121 from SC groups). Results EI and SC groups were comparable regarding demographics, premorbid and baseline characteristics, except the use of second-generation antipsychotic (SGA) treatment (EI patients were more likely to receive SGA than SC patients). EI patients had significantly shorter DUP than SC counterparts (p=0.015). Regarding follow-up outcomes, EI patients displayed lower levels of negative (p=0.044) and depressive symptoms (p=0.055), higher scores in RFS immediate social network (p=0.027) and lower rates of service disengagement (p=0.048) than SC patients even when SGA use and DUP were adjusted as covariates in analysis of covariance for comparison. There were no significant group differences in admission and suicide rates. Discussion Our results indicate that extended EASY service achieve favorable outcomes in adult FEP patients on shortening of treatment delay and improvement in negative symptoms and social functioning, and service disengagement reduction. Further evaluation is required to assess the sustainability of positive effects.

Exercise intervention and the sleep quality in relation with the procedural learning in psychosis

Sleep quality in psychosis has been reported to have abnormalities in terms of sleep efficiency, initiation, maintenance and total sleep time (Bromundt et al., 2011; Wulff et al., 2012; Wilson & Argyropoulos, 2012). Some have even argued that such sleep abnormalities may have caused a few cognitive symptoms in psychosis (e.g., Wamsley et al., 2011). In recent years, physical exercise has been reported to have significant effects in reducing cognitive symptoms in patients with psychosis. However, there is no up-to-date study that has investigated the correlation between physical exercise, sleep quality and the cognitive function of patients with psychosis. The aim of this study is to promote a 12-week physical exercise intervention to the psychotic population, and investigate whether the intervention can improve the sleeping quality as well as procedural memory performance. A randomised control trial has been carried out for this study. Patients with psychosis were recruited and randomly assigned to either a 12-week physical exercise intervention or a 12-week Carrom control intervention. Sleep quality (i.e., Insomnia Sleep Index; Bastien et al., 2001, Pittsburgh Sleep Quality Index; Buysee et al., 1988), cognitive function and clinical scale will be assessed before and after the 12-week intervention.

Predictors of service disengagement from EASY program in young psychosis patients: a 3-year follow-up study in Hong Kong

This journal suppl. contain Abstracts for the 14th International Congress on Schizophrenia ResearchBackground: Adverse social circumstances in childhood and adolescence increase vulnerability for adult psychotic disorders. Children who have psychotic- like experiences (PLEs) are at higher risk to develop psychotic disorders later in life. If PLEs are considered potential precursors of psychotic disorders and the risk for psychotic disorders develops in early life, PLEs in childhood should be related to indicators of social disadvantage. Methods: A self-report study assessing a sample of 1545 schoolchildren (45% Dutch, 26% Moroccan, 11% Turkish, 5% Western and 13% other non-Western) was conducted in the Netherlands (age range: 9-16). PLEs were measured with 8 items from the psychosis section of the K-SADS. Additional questions addressed impact of the PLEs. Measures of parental socio-economic status, neighborhood deprivation, perceived discrimination, parental separation, housing stability and degree of urbanization were used as indicators of social disadvantage, based on which a cumulative index of social disadvantage was created (low, medium, high). Results: The overall prevalence of any PLE with high impact was 6% (N = 93). Neighborhood deprivation, perceived discrimination and an unstable housing situation were associated with risk for PLEs. Age- and sex-adjusted Odds Ratios for any PLE with high impact were 1.83 (95% CI, 0.92-3.69) for medium and 2.28 (1.11-4.69) for high cumulative social disadvantage, compared to low social disadvantage. The risk was higher for ethnic minority youth compared to Dutch (Odds Ratio = 2.6; 95% CI, 1.6-4.3). The increased risk remained after adjusting for social disadvantage. Conclusion: The risk for PLEs with high impact was associated with indicators of social disadvantage. PLEs with high impact were more prevalent in ethnic minority youth than in Dutch youth. The increased risk was not explained by cumulative social disadvantage.Background: The risk for psychotic disorders is increased for many immigrant groups in several countries, particularly for those who migrated in early life and for second-generation immigrants. Social factors are likely to contribute to this increase, but biological pathways have hardly been explored. Since immune activation has been associated both with schizophrenia and social stress in early life, it may be involved in the pathway of migration, ethnic minority status and psychosis. Methods: Case-control study of 11 Dutch and 14 immigrant patients with first episode psychosis, and 14 Dutch and 10 immigrant healthy controls. Quantitative polymerase chain reaction (Q-PCR) techniques were used to measure mRNA levels of 97 genes in isolated monocytes. These genes were selected for their association with schizophrenia, bipolar disorder, autoimmune or inflammatory disorders in previous genome wide association studies. Results: Compared to Dutch controls, 29 genes in monocytes of Dutch cases were upregulated (fold changes more than two standard deviations (sd)) and statistical significance was reached for 13 genes. Most of these genes are involved in inflammation pathways, including coding for the pro-inflammatory cytokines IL-8, IL-1 beta and IL-6. Immigrant cases had a similar gene expression profile to Dutch cases. Twenty-four of the upregulated genes in patients had an increased expression in immigrant controls as well. The fold changes of an additional 14 genes was more than two sd for immigrant controls compared with Dutch controls. Conclusion: Inflammatory genes in monocytes were upregulated both in Dutch and in immigrant patients with first episode psychosis. Immigrant controls showed similar inflammatory gene expression to both patient groups and differed from Dutch controls. The findings suggest that childhood migration and second generation immigrant status may result in a shift of the distribution of immune activation in immigrant populations, which may contribute to the higher rates of psychotic disorders in these groups.Background: Many people with schizophrenia (50-80%) demonstrate impaired insight. A number of interventions aiming to improve insight have been proposed and evaluated, for example cognitive behavioral therapy and psycho-education. Results of these interventions leave room for improvement. Therefore, we propose a new intervention to improve insight in people with schizophrenia (REFLEX). REFLEX focuses on insight in ones functioning in everyday life and changes in general functioning after psychosis by improving metacognitive acts necessary for insight (selfreflectiveness, idiosyncratic self-certainty) and reducing stigma-sensitivity. Methods: The primary objective is to improve insight. By improving insight, we hope to improve functional outcome and symptoms. Results: 120 patients diagnosed with schizophrenia with poor insight and sensitive are included in a randomized controlled trial): REFLEX was compared to an active control condition consisting of group wise drill and practice cognitive remediation training. Preliminary analysis show that while clinical insight measures with the SAI-E remains unchanged, while cognitive insight measured with the BCIS improves in the REFLEX condition (F 1,85 4,9, p

Randomized controlled trial evaluating 1-year extended case management for first-episode psychosis patients discharged from EASY program in Hong Kong

This journal suppl. contain Abstracts for the 14th International Congress on Schizophrenia ResearchBackground: Adverse social circumstances in childhood and adolescence increase vulnerability for adult psychotic disorders. Children who have psychotic- like experiences (PLEs) are at higher risk to develop psychotic disorders later in life. If PLEs are considered potential precursors of psychotic disorders and the risk for psychotic disorders develops in early life, PLEs in childhood should be related to indicators of social disadvantage. Methods: A self-report study assessing a sample of 1545 schoolchildren (45% Dutch, 26% Moroccan, 11% Turkish, 5% Western and 13% other non-Western) was conducted in the Netherlands (age range: 9-16). PLEs were measured with 8 items from the psychosis section of the K-SADS. Additional questions addressed impact of the PLEs. Measures of parental socio-economic status, neighborhood deprivation, perceived discrimination, parental separation, housing stability and degree of urbanization were used as indicators of social disadvantage, based on which a cumulative index of social disadvantage was created (low, medium, high). Results: The overall prevalence of any PLE with high impact was 6% (N = 93). Neighborhood deprivation, perceived discrimination and an unstable housing situation were associated with risk for PLEs. Age- and sex-adjusted Odds Ratios for any PLE with high impact were 1.83 (95% CI, 0.92-3.69) for medium and 2.28 (1.11-4.69) for high cumulative social disadvantage, compared to low social disadvantage. The risk was higher for ethnic minority youth compared to Dutch (Odds Ratio = 2.6; 95% CI, 1.6-4.3). The increased risk remained after adjusting for social disadvantage. Conclusion: The risk for PLEs with high impact was associated with indicators of social disadvantage. PLEs with high impact were more prevalent in ethnic minority youth than in Dutch youth. The increased risk was not explained by cumulative social disadvantage.Background: The risk for psychotic disorders is increased for many immigrant groups in several countries, particularly for those who migrated in early life and for second-generation immigrants. Social factors are likely to contribute to this increase, but biological pathways have hardly been explored. Since immune activation has been associated both with schizophrenia and social stress in early life, it may be involved in the pathway of migration, ethnic minority status and psychosis. Methods: Case-control study of 11 Dutch and 14 immigrant patients with first episode psychosis, and 14 Dutch and 10 immigrant healthy controls. Quantitative polymerase chain reaction (Q-PCR) techniques were used to measure mRNA levels of 97 genes in isolated monocytes. These genes were selected for their association with schizophrenia, bipolar disorder, autoimmune or inflammatory disorders in previous genome wide association studies. Results: Compared to Dutch controls, 29 genes in monocytes of Dutch cases were upregulated (fold changes more than two standard deviations (sd)) and statistical significance was reached for 13 genes. Most of these genes are involved in inflammation pathways, including coding for the pro-inflammatory cytokines IL-8, IL-1 beta and IL-6. Immigrant cases had a similar gene expression profile to Dutch cases. Twenty-four of the upregulated genes in patients had an increased expression in immigrant controls as well. The fold changes of an additional 14 genes was more than two sd for immigrant controls compared with Dutch controls. Conclusion: Inflammatory genes in monocytes were upregulated both in Dutch and in immigrant patients with first episode psychosis. Immigrant controls showed similar inflammatory gene expression to both patient groups and differed from Dutch controls. The findings suggest that childhood migration and second generation immigrant status may result in a shift of the distribution of immune activation in immigrant populations, which may contribute to the higher rates of psychotic disorders in these groups.Background: Many people with schizophrenia (50-80%) demonstrate impaired insight. A number of interventions aiming to improve insight have been proposed and evaluated, for example cognitive behavioral therapy and psycho-education. Results of these interventions leave room for improvement. Therefore, we propose a new intervention to improve insight in people with schizophrenia (REFLEX). REFLEX focuses on insight in ones functioning in everyday life and changes in general functioning after psychosis by improving metacognitive acts necessary for insight (selfreflectiveness, idiosyncratic self-certainty) and reducing stigma-sensitivity. Methods: The primary objective is to improve insight. By improving insight, we hope to improve functional outcome and symptoms. Results: 120 patients diagnosed with schizophrenia with poor insight and sensitive are included in a randomized controlled trial): REFLEX was compared to an active control condition consisting of group wise drill and practice cognitive remediation training. Preliminary analysis show that while clinical insight measures with the SAI-E remains unchanged, while cognitive insight measured with the BCIS improves in the REFLEX condition (F 1,85 4,9, p