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Background: Functional remission (FR) is an intermediate and necessary step toward recovery, but is understudied in first-episode psychosis (FEP). We aimed to examine the rate and predictors of FR in FEP patients in the context of a randomized-controlled trial (RCT) comparing a 1-year extension of early intervention (Extended EI, 3-year EI) with step-down psychiatric care (SC, 2-year EI)., Methods: One hundred sixty Chinese patients were recruited from a specialized EI program for FEP in Hong Kong after they have completed this 2-year EI service, randomly allocated to Extended EI or SC, and followed up for 12 months. Assessments on premorbid adjustment and personality, clinical profiles, functioning, and treatment characteristics were conducted. FR was operationalized as simultaneous fulfillment of attaining adequate functional levels (measured by Social and Occupational Functioning Scale and Role Functioning Scale) and competitive employment at 6 and 12 months. Data analysis was based on 156 subjects who completed follow-up functional assessments., Results: Thirty-one (19.9%) patients achieved FR status. Multivariate binary regression analysis showed that female gender, lower degrees of premorbid schizoid-schizotypal traits, Extended EI treatment condition, lower levels of positive symptoms at intake, and better baseline functioning independently predicted FR., Conclusion: This is the first RCT providing supportive evidence to an extension of EI service beyond 2-year treatment duration on further enhancing the likelihood of FR attainment in FEP. Our findings that only approximately 20% of patients achieved FR indicate an unmet therapeutic need for promoting sustained adequate functional improvement in the early stage of psychotic illness., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The chronic and prevalent natures of schizophrenia result in long-term institutionalization for the patients. Conventional treatment of anti-psychotic medication on management of psychotic symptoms often brings on severe side effects and reduces patients' well-being. Tai-chi is a mind-body exercise that underscores motor coordination and relaxation. This 3-arm randomized controlled trial investigated the psychophysiological benefits of Tai-chi on 153 chronic schizophrenia patients, who were recruited from a mental health rehab complex and randomized into Tai-chi, exercise, or waitlist control groups. Both intervention groups received 12weeks of specific intervention plus standard medication received by the controls. All participants completed psychiatric interviews, self-report questionnaires, performance tasks, and salivary cortisol measures at baseline, 3-month, and 6-month follow-up on psychotic symptoms, motor coordination, memory, daily living function, and stress. Multigroup latent growth modeling was used to evaluate the intervention effects on the outcomes. Compared to controls, the Tai-chi group showed significant decreases in motor deficits and increases in backward digit span and mean cortisol, while the exercise group displayed significant decreases in motor deficits, negative and depression symptoms and increases in forward digit span, daily living function, and mean cortisol. The two interventions did not show significantly different therapeutic effects, except for fewer symptom manifestations in the exercise group. These results suggest psychophysiological benefits for Tai-chi on chronic schizophrenia patients in terms of motor coordination and memory. Though both Tai-chi and exercise groups tended to manifest fewer symptoms than the control group, the exercise group showed better symptoms management than the Tai-chi group., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Previous research investigating the relationships between avolition, cognition and functioning in schizophrenia mostly focused on chronic samples and were cross-sectional in design. Impacts of avolition and cognition on longitudinal functional outcome in first-episode patients are under-studied. We assessed 114 Chinese aged 18-55 years presenting with first-episode schizophrenia-spectrum disorder aiming to identify baseline predictors of 1-year functional outcome. Results showed that both avolition and global cognition independently predicted functioning, with avolition being the strongest predictor above and beyond cognition and other symptom dimensions. Our findings indicate the central role of in determining longitudinal functional status in the early illness stage., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Depressive symptoms are a distinct symptom dimension in psychotic disorders and are associated with elevated suicide risk, and poorer clinical and functional outcomes. Previous research on depressive symptoms mainly focused on chronic patients and few studies were conducted to investigate factors associated with depression in the early illness course. We aimed to examine the prevalence and risk factors of depressive symptoms, and their impacts on functioning, subjective quality of life (QoL) and self-efficacy in first-episode non-affective psychosis., Method: Three hundred fifty-one Hong Kong Chinese aged 26-55years presenting with first-episode non-affective psychosis to early intervention service were recruited. Assessments encompassing sociodemographics, premorbid adjustment, clinical and treatment profiles, functioning, QoL and perceived self-efficacy were conducted. Patients who had Calgary Depression Scale for Schizophrenia (CDSS) total score ≥6 were classified as having depressive symptoms., Results: Fifty-three (15.1%) patients exhibited depressive symptoms at entry. Depressed patients had worse functioning, poorer QoL and lower level of self-efficacy than non-depressed counterparts. Multivariate regression analysis showed that previous exposure to stressful life events, unemployment, being married, more severe positive symptoms, higher level of antipsychotic-induced Parkinsonism and negative attitude towards medication treatment were independently associated with depression status., Conclusions: Depressive symptoms were frequently observed in adult patients with first-episode nonaffective psychosis, and were linked to poor functioning and QoL. Our findings indicated that, aside from social and clinical risk factors, presence of drug-induced Parkinsonism and negative treatment attitude may render patients more vulnerable to developing depression in the early stage of psychotic illness., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Language disorganization is an important clinical indicator of acute psychosis, yet the longitudinal course and pathogenesis are not well understood. Executive dysfunction has been suggested as a vital contributor to formal thought disorder (FTD) and may serve as a stable predictor of symptomatic risk. The paper reports a one-year prospective study of language disorganization in sixty patients with first-episode schizophrenia-spectrum disorders and investigates executive function as a predictor of persistent FTD one year after illness onset. FTD was captured using the Clinical Language Disorder Rating Scale (CLANG), which segregates language abnormalities into three empirically validated levels: syntactic, semantic, and production. After one year, patients' syntactic and semantic deficits were substantially reduced, but production impairments persisted. Patients' improvement of semantic impairment was associated with reduced disorganized symptoms while production impairment was associated with negative symptoms. We further identified two different patterns of baseline executive function predictors for both residual semantic and production impairment. We found that sustained FTD at the semantic level was predicted by both sustained attention and planning at illness onset, while residual production failure was only predicted by sustained attention. In conclusion, the present paper documents the distinct characteristics of psycholinguistic levels in FTD and isolates two different patterns of executive function predictors for persistent semantic and production language disorganization at follow-up. The findings help to disentangle FTD dimensions at different levels of language production processes, which provide clinical implications for targeting patients at risk for prolonged FTD concordant upon executive dysfunction at illness onset., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Schizophrenia (SZ) and bipolar I disorder (BD) share many overlapping clinical features, confounding the current diagnostic systems. Recent studies suggest the posterior cingulate (PCC) and medial prefrontal (MPFC) cortices that are involved in SZ and BD pathophysiology. However, the roles of PCC and MPFC in providing specific distinctive and shared neural substrates between these two disorders remain largely unknown. Examining the neurophysiologic mechanism of these diseases may help explain the clinical observations and differentiate the two disorders., Methods: We used the Dynamic Casual Modeling (DCM), which is capable of eliciting hidden neuronal dynamics and reveal cross-regulation of multiple neuronal systems, to characterize the pattern of disrupted effective connectivity in the left PCC-MPFC circuit during working memory tasks in 36 SZ and 20 BD patients as well as 29 healthy controls., Results: Compared to the healthy controls, both SZ and BD patient groups exhibited significant negative effective connectivity from the left MPFC to PCC. The negative effective connectivity was more remarkable in schizophrenic patients. Only patients with BD differed from healthy controls with positive effective connectivity from the left PCC to MPFC., Conclusions: Whole brain analysis revealed deactivation of the left PCC and MPFC across all patient groups. This study provides new insight that changes in effective connectivity of the left MPFC to left PCC circuit during working memory processing may be a core pathophysiological feature distinguishing SZ from BD., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Individuals with first-episode psychosis (FEP) have markedly elevated risk for suicide. Previous research on suicidality in early psychosis mainly focused on attempted and completed suicide. Data regarding risk factors for suicidal ideation, which is a common antecedent and predictor of suicide attempt, were limited. This study aimed to examine the prevalence of suicidal ideation and its relationships with clinical, neurocognitive and psychological factors in FEP patients., Method: Eighty-nine Chinese patients aged 15 to 25years presenting with FEP to specialized early intervention service were recruited. A comprehensive set of assessments examining pre-treatment illness characteristics, symptom severity, neurocognitive function, and psychological factors were administered. Current suicidal ideation and history of suicide attempt were systematically evaluated., Results: Approximately 42% of patients expressed suicidal ideation after service entry. Univariate regression analyses found that suicidal ideation was significantly associated with past suicide attempt, depressive symptoms, emotion expressivity, hopelessness, future expectation, attentional impulsiveness, internal and external locus of control, and the likelihood of endorsing fear of social approval and survival and coping beliefs as reasons for living. Final multivariate model showed that previous suicide attempt, depression, less severe diminished expression, greater degree of hopelessness and lower level of internal locus of control independently predicted suicidal ideation., Conclusions: Suicidal ideation was prevalent in FEP patients. Our findings implied that close monitoring and prompt intervention of those potentially modifiable risk factors for suicidal ideation including depression, hopelessness and perceived inadequate personal control may reduce suicide risk in the early course of psychotic illness., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: Studies in healthy individuals show that exerting self-control consumes cognitive resources, which reduces subsequent self-control performance. Restoring the availability of blood glucose eliminates this impairment. Patients with schizophrenia are found to have self-regulatory dysfunctions. This study aims to investigate whether patient's (a) glucose facilitation effects will be impaired, and (b) will have exaggerated depletion in a self-control task., Method: 40 patients with schizophrenia-spectrum disorders and 40 normal controls were recruited. A two drinks (glucose vs. placebo)×two depleting phases (self-control depleted vs. non-depleted) between-groups design was used. We examined the blood glucose levels before and after the selfcontrol depletion phase and the subsequent performances in two self-control tasks (handgrip and Stroop tests) after the drink condition., Results: The four groups (depleting×glucose, depleting×placebo, non-depleting×glucose and nondepleting×placebo) of both patients and normal controls were comparable on a number of characteristics. The change in blood glucose level in the depleting group was significantly different from those in the non-depleting group. Two×two between-subjects ANOVAs were carried out to test the performances in the handgrip and Stroop tasks. Significant interactions were found in healthy controls regarding both tasks. However, a significant interaction was only found in patients regarding the handgrip task but not the Stroop task., Conclusions: This study demonstrated an abnormal glucose facilitation effect in patients during a cognitive self-control task but not during a physical self-control task. The findings also suggested for the first time that a self-control depletion effect is intact in patients with schizophrenia., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objectives: This study aims to examine the prevalence and predictors of disengagement in a longitudinal cohort of first-episode psychosis (FEP) patients., Methods: Seven hundred FEP patients aged 15 to 25 enrolled into the Early Assessment Service for Young People with Psychosis (EASY) from 2001 to 2003 were recruited into the study. Data on sociodemographics, clinical characteristics, baseline symptoms and functioning and medication adherence were collected. Rate and predictors of service disengagement were the outcomes of interest. Predictors were examined using Cox proportional hazards model., Results: Ninety four patients (13%) were disengaged from the EASY program. Fewer negative symptoms at initial presentation, a diagnosis other than schizophrenia-spectrum disorder and poorer medication compliance in the first month of treatment were significant predictors of disengagement from service., Conclusions: Early intervention teams should pay attention to factors associated with disengagement, and monitor at risk patients closely to detect signs of non-adherence., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: The adverse effects of a long duration of untreated psychosis (DUP) have been explored in numerous short-term studies. These studies support the development of early interventions that reduce treatment delay and promote recovery. However, the enduring impact of DUP is largely unknown, partly due to the paucity of prospective long-term studies. Although the DUP-outcome relationship is commonly assumed to be linear, the threshold effect has not been adequately examined., Objective: To explore the relationship between DUP and long-term symptomatic remission., Methods: This was a prospective study of a cohort of 153 first-episode psychosis patients in Hong Kong at the 13-year follow-up. The patients were categorized into short (≤30days), medium (31-180days) and long (>180days) DUP groups., Results: The long-term outcome was ascertained in 73% of the patients. Nearly half of the patients (47%) fulfilled the criteria for symptomatic remission. The short DUP group experienced a significantly higher remission rate over the course of the illness. The odds of long-term symptomatic remission was significantly reduced in the medium DUP (by 89%) and long DUP (by 85%) groups compared with the short DUP group. Further analysis showed that DUP had a specific impact on negative symptom remission., Conclusion: The findings support the threshold theory that DUP longer than 30days adversely impacts the long-term outcome. The present study is one of the few studies that confirmed the enduring impact of DUP on long-term outcomes based on well-defined criteria and adequate statistical adjustment., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Diminished expression (DE) is a core sub-domain of negative symptoms construct in schizophrenia. There is limited, yet inconsistent data regarding DE and its associations with cognition, particularly in the early illness course. This study aimed to examine cross-sectional and longitudinal relationships of DE with cognitive functions in first-episode schizophrenia utilizing a prospective design., Method: Ninety-three Hong Kong Chinese aged 18 to 55 years presenting with first-episode schizophrenia-spectrum disorder were studied. Severity of DE was measured as sum of individual item scores indicative of affect flattening and alogia. Symptom evaluation was conducted at intake, after clinical stabilization of first psychotic episode, at 12, 24 and 36 months. Cognitive functions were evaluated at clinical stabilization, 12, 24 and 36 months., Results: DE was significantly correlated with various cognitive functions in successive follow-up assessments. Regression analyses adjusting confounding effects of sex, pre-morbid adjustment, duration of untreated psychosis and chlorpromazine equivalents showed that DE was associated with performance on verbal fluency at 12 (p<0.01) and 24 months (p<0.05), visual reproduction at 24 (p<0.05) and 36 months (p<0.01), logical memory at 36 months (p<0.05) and Modified Wisconsin Card Sorting test at 24 (p<0.05) and 36 months (p<0.05). Neither cross-lagged associations between DE and cognition nor significant correlations between changes in these two domains over three years were observed., Conclusions: DE and cognitive functions were correlated concurrently but no longitudinal associations between these two domains could be demonstrated. Our findings indicated that DE and cognitive impairment represented relatively independent domains of the illness with potentially distinctive therapeutic implications., (Copyright © 2013 Elsevier B.V. All rights reserved.)

There has been increasing interest in studying the impact of physical activity on the psychological and physical well-being and functioning in patients with first-episode psychosis. The exploration of factors which contribute to physical activity in psychosis may open up opportunities for improvement of functional outcome. The purpose of this study was to examine the association between physical activity level and functioning in psychosis. A total of 283 patients with first-episode psychosis were recruited from a specialized early intervention service for adult-onset psychosis (Jockey Club Early Psychosis Project) in Hong Kong. The level of physical activity, sociodemographics and clinical characteristics was assessed at study entry. Functioning was assessed at 6-months period. Ninety-six (33.9%) patients were categorized as physically inactive, and 187 (66.1%) of them were physically active. Being physically inactive (β=0.163, P=0.003), having more positive and negative symptoms [SAPS total score (β=-0.161, P=0.005), and SANS total score (β=-0.202, P=0.001)], and having lower household income (β=0.207, P=0.001) at baseline predicted poorer functioning at 6months. Early intervention for psychosis should target to improve patients' physical activity level which may help subsequent functioning., (© 2013.)

Objective: Relapse is common among patients with psychotic disorders. Identification of relapse predictors is important for decision regarding maintenance medication. Naturalistic studies often identify medication non-adherence as a dominant predictor. There are relatively few studies for predictors where adherence is already known. It is this situation i.e., discontinuation of medication that predictors will be most useful. We identify predictors for relapse in situations of (i) discontinuation and (ii) continuation of maintenance medication., Method: Analysis of relapse predictors is based on a randomized controlled study (n=178) comparing relapse rates between patients who discontinued or continued medication for at least 1 year following first-episode psychosis. Demographic, clinical and neurocognitive variables were assessed at baseline as predictors of relapse within 1 year., Results: Risk of relapse was 79% in the discontinuation group and 41% in the maintenance group. Predictors in the discontinuation group were diagnosis of schizophrenia, poorer semantic fluency performance, and higher blink rate. Predictors in the continuation group were disinhibition soft signs and more general psychopathology symptoms., Conclusion: Different predictors of relapse were identified for first episode psychosis patients who discontinued and continued maintenance medication. Neurocognitive dysfunctions are important predictors for both groups. While signs of frontal dysfunction and dopamine hyperactivity predict relapse in the discontinuation group, sign of cognitive disinhibition predicts relapse in the continuation group., (© 2013 Elsevier B.V. All rights reserved.)

Background: Since the introduction of consensus criteria for symptomatic remission in 2005, most first-episode studies focused on cross-sectional relationship between remission status and functional outcome. Predictive validity of the proposed remission definition was under-studied. Relationship of remission with subjective quality of life (QoL) was inadequately addressed with inconsistent findings being observed., Method: One hundred and four Hong Kong Chinese aged 18 to 55years presenting with first-episode schizophrenia-spectrum disorder were studied. Socio-demographics, baseline clinical and functioning profiles were obtained. Psychopathological and functional reassessments were conducted at 6, 12 and 24months. Subjective QoL was measured at 12 and 24months. Symptomatic remission was operationally defined according to the consensus criteria developed by the Remission in Schizophrenia Working Group (RSWG), comprising both symptom-severity and 6-month duration components., Results: At 12months, 59.6% of patients achieved symptomatic remission. Remitted patients had significantly lower symptom severity, more favorable psychosocial functioning and better subjective QoL at 12months than non-remitted counterparts. Attainment of remission at 12months was significantly associated with fewer positive, negative, depressive and disorganization symptoms, higher levels of functioning and subjective QoL at 24months. Linear regression analysis indicated that remission status independently predicted functional outcome even when the effects of educational level, baseline functioning and negative symptom scores were controlled for., Conclusion: The operationally defined symptomatic remission formulated by the RSWG represented a clinically valid construct that was found to be closely related to both concurrent and longitudinal outcomes on psychopathology, functioning and subjective QoL in the early stage of schizophrenia., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Semantic categorization abnormalities have been observed in schizophrenia, but studies have rarely focused on the longitudinal trajectory. In this study, we consider semantic performance and the relationship with symptomatic changes during recovery from a first-episode of schizophrenia over a period of 3 years. Thirty-seven first-episode patients with schizophrenia were compared to thirty-seven matched controls in a categorization task. Patients were assessed at first episode, after clinical stabilization, and annually for the subsequent 3 years. In the task, participants indicated whether a word belonged to a given category. Each category contained words of varying degrees of semantic relatedness: typical, atypical, borderline, related-but-outside, and unrelated. Reaction times and proportion of 'yes' responses were analyzed. At first assessment, semantic categorization abnormalities were observed in first-episode patients. Patients assigned more semantically-dissimilar words to the categories than controls. As patients stabilized from acute states, their semantic categorization performance improved and then remained stable throughout the entire follow up period of 3 years. Interestingly, semantic performance deficits, particularly a diminished typicality effect, correlated with negative symptoms in the initial episode, but not at stabilization when symptoms subsided. No significant associations between positive and negative symptoms, or pre-defined categorization measures were identified. The data demonstrated semantic memory abnormalities in first-episode schizophrenia. However, an improvement of semantic categorization performance was observed in stabilized schizophrenia patients. Overall, the data are suggestive of a state effect in semantic abnormalities rather than a trait effect. The correlation between degree of impairment and symptoms may explain previous inconsistent findings., (Copyright © 2012 Elsevier B.V. All rights reserved.)

In recent decade, deficits in the mechanism of Supervisory Attentional System (SAS) have become increasingly influential in explaining the nature of dysexecutive syndrome experienced by schizophrenic patients. The SAS model is characterized by having a detailed sub-classification of specific executive function components, among which semantic inhibition has been investigated using the Hayling Sentence Completion Test (HSCT). Several studies thus far have indicated that schizophrenic patients show impairment in HSCT performance. However, HSCT data concerning first-episode patients is still scarce. Besides, as previous HSCT studies were all cross-sectional in nature, they were not able to assess changes in HSCT performance over time. In order to address the paucity of knowledge about the longitudinal trajectories and correlates of semantic inhibition deficits in early schizophrenia, this paper reports a three-year prospective study of HSCT performance in medication-naïve, first-episode patients with schizophrenia-spectrum disorders. HSCT performance was assessed in 34 patients at four times over a period of three years, while the 34 healthy controls were assessed once. We found that medication-naïve patients demonstrated impairment in the inhibition condition in HSCT as compared to controls, but not in the initiation condition. Such HSCT impairment gradually improved in the three years following the first psychotic episode; however, HSCT performance did not predict improvement in negative or positive symptoms over the three-year period. The present findings suggest that semantic inhibition impairment is a specific deficit in schizophrenia that may require early intervention efforts, with the goal of facilitating more successful verbal communication and thereby better interpersonal functioning., (Copyright © 2011 Elsevier B.V. All rights reserved.)

This study aims to explore the relationship between clinical symptoms and cognitive functions with different insight dimensions in patients with first-episode schizophrenia. Seventy-nine patients were assessed following six months of treatment. Insight was assessed using the abridged version of Scale of Unawareness of Mental Disorder (SUMD). Symptoms were assessed using Positive and Negative Syndrome Scale (PANSS). Cognitive functions were assessed using the Modified Wisconsin Card Sorting Test (MWCST), semantic verbal fluency and the letter-number sequencing (LNS) test from the Wechsler Adult Intelligence Scale (WAIS). Positive, negative and disorganized symptoms were found to be correlated with overall insight and all three general insight dimensions. Only perseverative errors and categories completed of MWCST were correlated with overall insight. Perseverative errors and non-perseverative errors of MWCST were correlated with the awareness of medication effects; perseverative errors of MWCST were also correlated with the awareness of social consequence of the illness. These support the link between poor insight and impaired executive function particularly measured by MWCST. The specific correlation of cognitive functions and different dimensions of insight suggests different underlying mechanism within each dimension of insight. The combined model of symptomatology and cognitive function explained 20.6% to 36.4% of the variance in the lack of insight within the different dimensions. The modest combined relationship of clinical and cognitive function with insight suggests that the exploration of other models in relationship to different insight dimensions is important., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Ideas and delusions of reference (IOR/DOR) are an important but underrecognized research target. Difficulty in their reliable assessment has been a barrier. A screening and assessment tool incorporating a self-information processing framework, the Ideas of Reference Interview Scale (IRIS), was developed and validated in patients with early psychosis., Methods: Comprehensive review of IOR/DOR phenomena in the literature and pilot interviews were conducted for scale item development. Self-referential themes were summarized into 15 items. A consecutive sample of 137 outpatients with early psychosis was interviewed using IRIS. Their IOR/DOR experiences were also rated independently by clinicians on the Scale for the Assessment of Positive Symptoms (SAPS) and self-rated using the IOR subscale on the Schizotypal Personality Questionnaire (SPQ). Inter-rater reliability of IRIS was examined in a subsample of 15 participants., Results: IRIS demonstrated good internal consistency (Cronbach's alpha 0.80), inter-rater reliability (intraclass correlation coefficient 0.95), and divergent validity with other symptoms. IRIS correlated satisfactorily with the IOR/DOR item or subscale on SAPS and SPQ (Spearman's rho = 0.71 and 0.47, respectively)., Discussion: IRIS provided a reliable high-resolution tool for progressing single-symptom research into IOR/DOR, a potential target feature of schizophrenia. The scale allows future investigation into self-referential processing and detailed phenomenological comparison in different clinical, subclinical, and healthy populations., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Negative symptoms are a core feature of schizophrenia. The evolution and trajectory of primary negative symptoms were under-studied. We aimed at evaluating the prevalence and stability of primary negative symptoms, and factors associated with persistent primary negative symptoms in a first-episode sample., Method: Ninety-three Hong Kong Chinese aged 18 to 55 years presenting with first-episode schizophrenia-spectrum disorder were studied. Data on premorbid adjustment, socio-demographics, and baseline clinical and cognitive profiles were obtained. Psychopathological and vocational reassessments were conducted at 12, 24 and 36 months. Primary negative symptoms were defined as the presence of clinically significant negative symptoms excluding depression and extra-pyramidal signs., Results: At baseline, 25.8% of subjects exhibited primary negative symptoms. A quarter of patients had their initial primary negative symptoms status retained 12 months after treatment initiation. In both Year 2 and Year 3 of study period, around 70% of subjects had their primary negative symptoms status maintained for 12 months. At the end of three-year follow-up, 23.7% were categorized as having persistent primary negative symptoms. Male sex, unemployment at intake, prolonged duration of untreated psychosis, poorer premorbid academic and social functioning, poorer insight and worse vocational outcome were found to be associated with persistent primary negative symptoms., Conclusion: Clinical status of primary negative symptoms in first-episode schizophrenia-spectrum disorder was unstable in the initial year of treatment. Baseline symptom assessment may not reliably predict development of persistent primary negative symptoms. Studying negative symptoms should take into account the longitudinal perspective, especially in the early course of psychotic disorders., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Executive function impairment is a key cognitive deficit in schizophrenia. However, traditional neuropsychological tests of executive function may not be sensitive enough to capture the everyday dysexecutive problems experienced by patients. Additionally, existing literature has been inconsistent about longitudinal changes of executive functions in schizophrenia. The present study focuses on examining the longitudinal change of executive functions in schizophrenia using the Modified Six Elements Test (MSET) that was developed based on the Supervisory Attentional System model and shown to be sensitive to everyday dysexecutive problems. In the present study, MSET performance was assessed in 31 medication-naïve first-episode schizophrenic patients at four times over a period of three years, while the 31 normal controls were assessed once. Patients demonstrated impairment in MSET as compared to controls. Importantly, the MSET impairment persisted from the medication-naïve state to clinical stabilization and the three years following the first psychotic episode though patients improved in a conventional executive test (Modified Wisconsin Card Sorting Test). Performance was not related to intelligence, educational level, symptom changes, age-of-onset, or duration of untreated psychosis. Better MSET performance at medication-naïve state predicted improvement in negative and positive symptoms over the three-year period. These findings may suggest that MSET impairment is a primary deficit in schizophrenia that occurs early in the course of the illness and remains stable irrespective of clinical state for at least three years following the first episode of schizophrenia., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Objective: This study is to explore the prevalence and risk factors for self-reported criminal behavior among persons with schizophrenia in rural China., Methods: We used data from a 14-year prospective follow-up study (1994-2008) of criminal behavior among a cohort (N=510) of persons with schizophrenia in Xinjin County, China., Results: The rate of criminal behavior was 10.0% among persons with schizophrenia in a rural community during the follow-up period. Bivariate analyses showed that the risk of criminal behavior was significantly associated with being male, unmarried, previous violent behavior, homelessness, no family caregivers, and high scores on measures of total symptoms of illness. In multivariate logistic regression analyses being male and previous violent behavior were identified as independent predictors of increased criminal behavior in persons with schizophrenia in the follow-up period., Conclusions: Criminal behavior is a common phenomenon among patients with schizophrenia in rural China. The findings of the risk factors for criminal behavior should be considered in planning mental health interventions for high-risk patients and their families., ((c) 2010 Elsevier B.V. All rights reserved.)

We report the first voxel-based morphometric (VBM) study to examine cerebral grey and white matter and cerebrospinal fluid (CSF) using computational morphometry in never-medicated, first-episode psychosis (FEP). Region-of-interest (ROI) analysis was also performed blind to group membership. 26 never-medicated individuals with FEP (23 with DSM-IV schizophrenia) and 38 healthy controls had MRI brain scans. Groups were balanced for age, sex, handedness, ethnicity, paternal socio-economic status, and height. Healthy controls were recruited from the local community by advertisement. Grey matter, white matter, and CSF: global brain volume ratios were significantly smaller in patients. Patients had significantly less grey matter volume in L and R caudate nuclei, cingulate gyri, parahippocampal gyri, superior temporal gyri, cerebellum and R thalamus, prefrontal cortex. They also had significantly less white matter volume in the R anterior limb of the internal capsule fronto-occipital fasciculus and L and R fornices, and significantly greater CSF volume especially in the R lateral ventricle. Excluding the 3 subjects with brief psychotic disorder did not alter our results. Our data suggest that fronto-temporal and subcortical-limbic circuits are morphologically abnormal in never-medicated, schizophrenia. ROI analysis comparing the schizophrenia group (n=23) with the healthy controls (n=38) confirmed caudate volumes were significantly smaller bilaterally by 11%, and lateral ventricular volume was significantly larger on the right by 26% in the patients. Caudate nuclei and lateral ventricular volume measurements were uncorrelated (Pearson correlation coefficient 0.30, p=0.10), ruling out the possibility of segmentation artefact. Ratio of lateral ventricle to caudate volume was bilaterally significantly increased (p<0.005, 2-tailed), which could represent an early biomarker in first-episode, never-medicated schizophrenia.

Many studies have shown that schizophrenia is associated with a wide range of cognitive impairments. Empirical findings suggest that patients with schizophrenia suffer from a "dysexecutive syndrome". However, the extent to which a general decline in neuropsychological function accounts for symptoms of executive dysfunction in schizophrenia is not clear. In this study, we examined further the nature and pattern of executive function in a sample of medication-naïve patients experiencing a first-episode of schizophrenia with a set of tests capturing the specific components of executive function. We also compared the performance of this clinical group with healthy controls. A total of 78 medication-naïve patients with first episode schizophrenia were recruited from the Early Assessment Service for Young People with Psychosis (EASY). Another 60 healthy controls were recruited for comparison. All subjects participated in a comprehensive set of executive function tests assessing initiation, sustained attention, online updating, switching, attention allocation, inhibition, and non-executive function. The executive function of patients with first-episode schizophrenia was found to be compromised relative to healthy controls. However, unlike patients with established schizophrenia, first episode patients exhibited only a limited deficit in sustained attention. Moreover, the majority of executive function deficits did not correlate with intellectual functioning and memory impairment in a sub-group of first episode patients without intellectual impairment. These findings suggest that first-episode patients exhibit a specific pattern of executive dysfunction compared to healthy controls and patients with an established illness. This differential breakdown of executive function components is unlikely to be an artefact of general intellectual decline or memory impairment in schizophrenia.

We examined the fractionation of executive functioning performance in ninety patients with schizophrenia, who were tested for initiation, sustained attention, switching/flexibility, attention allocation and impulsivity/disinhibition. The participants were also given tests of general intelligence and memory. We analysed the executive functioning performance of individual patients against normative data from our laboratory, and summary scores for all of the executive functioning components were computed. For each component, participants were classified as having impairment with a test performance of 1.5 standard deviations or more from the norm of the corresponding test. Of all of the participants, 27.8% (n=25) demonstrated poor performance in all of the components, and 5.6 % (n=5) exhibited intact or fair performance in all of the components. Furthermore, 18.9% (n=17) showed intact or fair performance in one component, 16.7% (n=15) in two components, 21.1% (n=19) in three components and 10% (n=9) in four components. The groups did not differ in education, gender or duration of illness, but the group that showed impaired performance in all of the components demonstrated the most severe psychotic symptoms after controlling for background intelligence, age and medication. The differential breakdown for the executive functioning performance across the participants suggests that the fractionation of central executive functioning occurs in schizophrenia.

Memory of contextual information is essential to one's quality of living. This study investigated if the different components of prose memory, across three recall conditions: first learning trial immediate recall, fifth learning trial immediate recall, and 30-min delayed recall, are differentially impaired in people with schizophrenia, relative to healthy controls. A total of 39 patients with schizophrenia and 39 matched healthy controls were recruited. Their prose memory, in terms of recall accuracy, temporal sequence, recognition accuracy and false positives, commission of distortions, and rates of learning, forgetting, and retention were tested and compared. After controlling for the level of intelligence and depression, the patients with schizophrenia were found to commit more distortions. Furthermore, they performed poorer on recall accuracy and temporal sequence accuracy only during the first initial immediate recall. On the other hand, the rates of forgetting/retention and recognition accuracy were comparable between the two groups. These findings suggest that people with schizophrenia could be benefited by repeated exposure to the materials to be remembered. These results may have important implications for rehabilitation of verbal declarative memory deficits in schizophrenia.

Background: Cognitive predictors of relapse have been extensively explored only in few long term longitudinal studies of first-episode schizophrenia., Method: This study prospectively followed 93 patients with first-episode schizophrenia, schizophreniform disorder, and schizoaffective disorder for 3 years after their first-episode illness. Cognitive domains including verbal intelligence, verbal and visual memory, verbal fluency, and Wisconsin Card Sorting Test performance were investigated as potential predictors of relapse., Results: We found that by the first year 21% patients had relapsed, by the second year 33% had relapsed, and by the third year 40% had relapsed. There was a significant difference in the relapse rate between patients with good adherence and patients with poor adherence to medication regimes. A multiple logistic regression analysis revealed that after controlling for medication adherence, perseverative error in the Wisconsin Card Sorting Test was the only cognitive function that significantly predict relapse with an odds ratio of 2.4., Conclusions: Cognitive flexibility in set shifting is related to tendency towards relapse in first-episode schizophrenic patients. Other cognitive factors appear not to be related to relapse. Possible mechanisms included the link between prefrontal dysfunction and sub-cortical dopamine system stability, as well as the effects of executive dysfunction on insight impairment and adherence behavior.

Mismatch negativity (MMN) is an event-related potential measure of auditory change detection. It is widely reported to be smaller in patients with schizophrenia and may not improve along with otherwise successful clinical treatment. The main aim of this report is to explore ways of measuring and presenting four features of frequency-deviant MMN dipole sources (dipole moment, peak latency, brain location and orientation) and to relate these to the processes of psychopathology and illness progression. Data from early onset patients (EOS) at the start of the illness in adolescence, and others who had their first break in adolescence 15 years ago (S-15Y) were compared with two groups of age-matched healthy controls (C-EOS, C-15Y). A four-source model fitted the MMN waveform recorded from all four groups, whether MMN amplitude was more (EOS) or less (S-15Y) reduced. The locations were in the left superior temporal and anterior cingulate gyri, right superior temporal and inferior/mid frontal cortices. Dipole latencies confirmed a bottom-up sequence of processing and dipole moments were larger in the temporal lobes and on the left. Patients showed small dipole location changes that were more marked in the S-15Y than the EOS group (more rostral for the left anterior cingulate, more caudal for the right mid-frontal dipole) consistent with illness progression. The modelling of MMN dipole sources on brain atlas and anatomical images suggests that there is a degree of dissociation during illness between small progressive anatomical changes and some functional recovery indexed by scalp recordings from patients with an onset in adolescence 15 years before compared to adolescents in their first episode.

Neurological soft signs are biological traits that underlie schizophrenia and are found to occur at higher levels in at-risk individuals. The expression of neurological soft signs may be modifiable during the onset of the first psychotic episode and the subsequent evolution of the illness and its treatment. This study investigates neurological soft signs in 138 patients with first-episode schizophrenia and tracks the expression of motor soft signs in the following 3 years. For the 93 patients who have completed the 3-year follow-up, we find that neurological soft signs are stable in the 3 years that follow the first psychotic episode, and that neurological soft signs are already elevated at the presentation of first-episode psychosis in medication-naive subjects. The level of neurological soft signs at clinical stabilization is lower for patients with a shorter duration of untreated psychosis. Although the quantity of neurological soft signs does not significantly change in the 3 years that follow the first episode, the relationship between neurological soft signs and negative symptoms does not become apparent until 1 year after the initial episode. A higher level of neurological soft signs is related to a lower educational level and an older age at onset, but the level of neurological soft signs does not predict the outcome in terms of relapse or occupational functioning.

In the Stroop test, interference occurs in naming the print color of a word when the word is itself the name of another color. Facilitation occurs when the word is the same as the print color. Previous studies on selective attention in schizophrenia using the Stroop interference effects have yielded contradicting results. Constraints included limited sample size and the recruitment of medicated chronic patients. We studied the Stroop interference and facilitation effects in a relatively large sample of first-episode schizophrenic patients (n=56), a substantial proportion of whom were medication-naïve (n=30) at the time of initial testing. We have also carried out longitudinal follow-up assessments when patients reached a clinically stable state, as well as 4months after recovery from the episode. We found that the Stroop interference effect was not increased in first-episode schizophrenic patients, whether medication-naïve or not. This effect did not change over the follow-up period. In addition, we detected an increase in Stroop facilitation effect in medicated schizophrenic patients, but only in the initial assessment soon after they had received medication. After sustained treatment, the increase in facilitation was normalized. These observations supported previous findings of a normal Stroop interference effect amongst schizophrenic patients. The increased facilitation effect for patients in their early phase of treatment (but not later) may represent an acute effect of anti-psychotic medication. Its nature and significance require further investigation.

We employed a simple and relatively undemanding task of monotone counting for the assessment of sustained attention in schizophrenic patients. The monotone counting task has been validated neuropsychologically and is particularly sensitive to right prefrontal lesions. We compared the performance of schizophrenic patients with age- and education-matched controls. We then explored the extent to which a range of commonly employed neuropsychological tasks in schizophrenia research are related to attentional impairment as measured in this way. Monotone counting performance was found to be correlated with digit span (WAIS-R-HK), information (WAIS-R-HK), comprehension (WAIS-R-HK), logical memory (immediate recall) (Weschler Memory Scale, WMS), and visual reproduction (WMS). Multiple regression analysis also identified visual reproduction, digit span and comprehension as significant predictors of attention performance. In contrast, logical memory (delay recall) (WMS), similarity (WAIS-R-HK), semantic fluency, and Wisconsin Card Sorting Test (perseverative errors) were not correlated with attention. In addition, no significant correlation between sustained attention and symptoms was found. These findings are discussed in the context of a weakly modular cognitive system where attentional impairment may contribute selectively to a range of other cognitive deficits.