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Background: This study aimed to conduct a systematic review and meta-analysis on cognitive performances of patients with treatment-resistant schizophrenia (TRS) after clozapine treatment and to examine the potential effect of follow-up duration and clozapine dosage., Methods: Five electronic databases were searched and studies were included if treatment-resistant schizophrenia patients were treated with clozapine and with baseline and follow-up cognitive functions assessments. Cognitive measures were categorised into six domains based on DSM-5-TR. Random-effect model analysis was used to pool the effect estimates. Moderator effects of clozapine dosage, follow up duration, duration of illness, age, years of education and change in positive symptoms severity were examined with meta-regression., Findings: Nineteen articles were included with 50 cognitive measures reported. Systematic review found inconsistent results. Twelve cognitive measures were included for meta-analysis and found overall improvement of cognitive performances after clozapine treatment SMD = 0.11 [95 % CI 0.02, 0.20] (p = 0.021). Patients with younger age, more years of education and improvements in positive symptoms are more likely to improve in cognitive performances. Subgroup analysis found significant improvement in studies with follow-up periods of 6-months or longer but not for studies with shorter follow-up periods., Conclusion: Clozapine may improve some domains of cognitive function, particularly over a longer period. However, the overall inconsistent results suggest that more studies with larger sample size and standard cognitive function assessments would be needed to enhance our understanding of the impact of clozapine on the cognitive functions in the TRS patients., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Backgrounds: This study explores the longitudinal changes and trajectories of cognitive functions in patients with adult-onset first-episode schizophrenia (FES) over four years and their relationships with the baseline subdomains of negative symptoms., Methods: A total of 177 patients of age 25-55 with FES were recruited. Baseline demographics, clinical, social and cognitive functions were assessed. Diminished expression and diminished motivation of negative symptoms were assessed with Scale for the Assessment of Negative Symptoms (SANS). Patients had yearly follow-up of cognitive function assessments over four years. Latent class growth analysis (LCGA) and mixed linear regression model were used to explore the longitudinal changes of cognitive functions and the effect of baseline negative symptoms on the longitudinal cognitive function changes. Relationships of baseline negative symptoms subdomains and cognitive functions were also explored., Results: Two trajectories of cognitive functions were identified. Longitudinal improvements were found in most cognitive functions apart from the logical memory. One trajectory of patients had significant deterioration of logical memory while the other group had significant improvement. Baseline diminished expression was associated with baseline and longitudinal changes of processing speed and verbal fluency while diminished motivation was associated with baseline and longitudinal changes of processing speed., Conclusions: Adult-onset FES patients had a homogeneous longitudinal improvement in most cognitive functions but not for logical memory suggesting the unique nature of verbal memory. The distinct relationship between baseline subdomains of negative symptoms with baseline and longitudinal cognitive functions suggesting the presence of differential overlapping etiology between negative symptom subdomains and cognitive functions., Competing Interests: Declaration of competing interest Prof Eric Yu Hai is the convener of the work group of the early intervention service of the Hospital Authority of Hong Kong. Dr. Sherry Kit Wa Chan, Dr. Wing Chung Chang, Dr. Edwin Ho Ming Lee are members of the work group of the early intervention service of the Hospital Authority of Hong Kong. All other authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Mindfulness meditation (MM) and its alignment with the mind-body perspective of health in Chinese cultures indicate its potential to benefit Chinese patients with psychosis. This is the first systematic review and meta-analysis to address the following questions: (1) Does MM improve clinical, well-being, and third-wave outcomes (i.e., mindfulness, acceptance, and compassion levels) among Chinese patients with psychosis? (2) What are the patient- and/or intervention-specific factors that moderate the efficacy of MM? (3) Are improvements on third-wave outcomes associated with improvements on clinical and well-being outcomes? (4) What are the mechanisms underlying the effects of MM? Evidence synthesized from 23 relevant articles (20 studies) involving 1749 patients showed that (1) MM improved a wide range of patients' outcomes, most consistently and sustainably for insight, rehospitalization duration, recovery rate, and social functioning; (2) age and duration of illness, but not the cumulated intervention hours, moderated the overall efficacy of MM; (3) post-MM improvements on mindfulness and on clinical and well-being outcomes were related, and (4) the effects of MM on patients' outcomes may be driven by its ability to promote positive changes in personal growth and enhance one's coping with the illness and its symptoms. Our data showed preliminary support for the benefits of MM in Chinese patients with psychosis. However, results should be considered in light of the varying quality of included studies and their heterogeneity in multiple aspects. Further research is needed to deduce the sustainability of MM's effects, its active ingredients, underlying mechanisms, and additional moderators of its efficacy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ideas of reference (IOR) are often implicated in predicting psychosis onset. They have been conceptualized to present on a continuum, from oversensitive psychological reactions to delusional thoughts. It is however unknown to what extent IOR may be triggered by collective environmental stress. We obtained timely data from 9873 individuals to assess IOR in relation to trauma exposure in the 2019-2020 social unrest in Hong Kong. Two levels of IOR are distinguished: attenuated IOR (IOR-A), being the experience of feeling particularly referred to within a group; and exclusive IOR (IOR-E), the experience of feeling exclusively referred to while others are not. Logistic regressions showed that event-based rumination was a shared predictor for IOR-A (OR = 1.07, CI = 1.03-1.10) and IOR-E (OR = 1.09, CI = 1.02-1.17). For IOR-A, three categories of social unrest-related traumatic events (TEs) were significant predictors, including being attacked or having experienced sexual violence (OR = 4.14, CI = 1.93-8.85), being arrested (OR = 4.48, CI = 1.99-10.10), and being verbally abused (OR = 2.66, CI = 1.28-5.53). Being arrested was significant for IOR-E (OR = 3.87, CI = 1.03-14.52), though not when rumination was included. Education level also significantly predicted IOR-E (OR = 0.72, CI = 0.52-0.99). Further analysis revealed that rumination significantly mediated between TEs and IOR severity (β = 0.26, SE = 0.01, CI = 0.24-0.28). The findings are consistent with the hypothesis that IOR-A and IOR-E occur as levels on a continuum, but each has some distinctive correlates. Extrinsic events may play a more prominent role in IOR-A, while intrinsic factors, such as cognitive capacity, may play a more prominent role in IOR-E. The involvement of rumination across the IOR spectrum suggests an opportunity for intervention., Competing Interests: Declaration of competing interest The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article, all outside of the current submitted work: EYHC has received speaker honoraria from Otsuka and DSK BioPharma, research funding from Otsuka, participated in paid advisory boards for Janssen and DSK BioPharma, and received funding to attend conferences from Otsuka and DSK BioPharma. All other authors declare no competing interests., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Self-referential gaze perception (SRGP)-the perception that others' gaze is towards oneself-is a core experience in patients with schizophrenia, and may be related to common delusional themes such as delusions of reference. Studies exploring SRGP bias in schizophrenia are limited and results have been inconsistent, particularly regarding its relationship with symptomatology and cognition. Seventy-five patients with schizophrenia-spectrum disorders (25 with high level of reference delusion, 25 with low reference delusion and 25 in clinical remission) and 25 matched healthy controls were compared in a gaze perception task to judge whether averted gaze with varied ambiguity was directed at them. All subjects were assessed with delusion and reference ideations and cognitive functions. Psychotic symptoms were assessed in patients. Gaze perception analysis adopted both behavioural and psychophysical approaches. Group differences and predictors of SRGP in ambiguous and unambiguous conditions were investigated. Both groups of symptomatic patients displayed higher ambiguous SRGP rate, and the group with high reference delusions showed more unambiguous SRGP bias. Cognitive functions were negatively associated with SRGP rate while positive and negative symptoms were positively associated. Cognitive function was the only significant predictor for ambiguous-SRGP rate. Patients with psychotic symptoms have hypermentalization of gaze perception as towards oneself, whereas patients with delusions of reference have more profound bias in gaze perception. General cognition is implicated in SRGP rate. Future studies could investigate interventions with targeted psychopathological profiles by improving non-social cognitive functions to test the hypothesis that cognitive functioning is related to SRGP bias and delusional beliefs., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

While antipsychotics (APs) could provide rapid relief of positive symptoms in psychotic disorders, their usage is often associated with side effects, stigma and inconveniences. For these and other reasons, many psychosis patients, particularly those of first-episode psychosis (FEP) in remission, wish to discontinue maintenance treatment. The current review aims to discuss the strategies of AP treatment following remission from FEP, with particular emphasis on the evaluation of outcomes following AP discontinuation. Upon review of relevant literature, three potential strategies are put forth for treatment-responsive, remitted FEP patients: a) life-long maintenance treatment, b) AP discontinuation during second year of treatment, or c) AP discontinuation after three years of treatment. In theory, the first strategy presents the safest option for maximal symptom control. However, a rigorous RCT indicates that if AP discontinuation is to be attempted, the third strategy best prevents poor long-term clinical outcomes. Further data is needed to address the costs and benefits of each treatment strategy, compare AP-free patients with those on different types of APs, as well as explore even longer-term outcomes., Competing Interests: Declaration of competing interest E.Y.H.C. reports having received speaker honoraria from Otsuka and DSK BioPharma; received research funding from Otsuka; participated in paid advisory boards for Jansen and DSK BioPharma; received funding to attend conferences from Otsuka and DSK BioPharma. The remaining authors declare no competing interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This study explored the 10-year trajectories and outcomes of negative symptoms in patients with first-episode schizophrenia-spectrum disorder. Patients were from the historical control study comparing 10-year outcomes between standard care and early intervention services. A total of 298 patients were identified, 214 were successfully interviewed at 10-year follow-up for clinical and functional outcomes and 209 patients were included for final analyses. Information from clinical records were obtained systematically using standardized data entry forms. These information including negative symptoms, hospitalization and employment, monthly for year 1-3 and trimonthly for the year 4-10. Hierarchical cluster analysis was used to explore the 10-year negative symptom clusters. Demographics and early clinical characteristics related to the cluster memberships and different components of negative symptom at 10-year follow-up were further explored. The cluster analysis identified three longitudinal clusters of negative symptoms and 15% of patients were in the relapsed group. There was no difference in cluster membership between the intervention groups. Male gender and duration of hospitalizations in year four were found to be significant determinants of relapse negative symptoms. Lower education level, higher year-one negative symptom score and more months of unemployment during the first 3 years predicted overall negative symptoms at 10-year follow-up. Male gender was found to be a predictor only for avolition and anhedonia and duration of untreated psychosis only predicted anhedonia. These results highlighted the heterogeneity of longitudinal outcomes and the importance of personalized interventions., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Achieving functional recovery in patients with psychosis is a challenge in clinical practice. Investigating the complex interplay between cognition, symptoms, insight and functional outcome in first episode psychosis will be crucial to understanding the factors leading to better functioning., Methods: In this 12-month prospective follow-up study, we investigated how cognition, clinical symptoms, and insight into illness affected overall functioning in 160 patients with first episode psychosis recruited from the Early Assessment Service for Young People with Psychosis (EASY) in Hong Kong from July 1, 2014 to June 30, 2016. Cognition was assessed at baseline while symptoms, insight, and functioning were assessed at 12-month follow-up. Structural equation modelling was used to examine the direct and indirect relationships between functioning and other latent constructs., Results: Symptoms (negative symptoms and general psychopathology) and insight were shown to be significant mediators between cognition and functioning. The significant direct relationship between cognition and functioning (β = 0.387; p < 0.001) became insignificant (β = 0.079; p = 0.578) after including symptoms and insight in the model. Symptoms and insight were significantly associated with cognition (symptoms, β = -0.469; p < 0.001; insight, β = -0.372; p < 0.001) and predicted functioning (symptoms, β = -0.558; p < 0.001; insight, β = -0.264; p < 0.01)., Conclusion: Symptoms and insight mediated the effects of cognition on functioning. Interventions for improving functioning in patients with first episode psychosis should target not only cognition but also symptoms and insight., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The long-term recovery rate of patients with schizophrenia-spectrum disorders has been persistently low despite the implementation of early intervention (EI) services internationally. It is, therefore, important to identify the modifiable factors during the early stage of the illness that predict long-term remission and recovery. The aim of this study is to explore the predictive value of the early stage clinical factors on the clinical remission and functional recovery at 10-year follow-up of patients with schizophrenia-spectrum disorders who received a 2-year EI service. Patients who received the EI service throughout the region of Hong Kong between 1st July 2001 and 30th June 2002 and with a diagnosis of schizophrenia-spectrum disorder were identified from the centralized hospital database (Clinical Management system, CMS). Semi-structured clinical interview was conducted at 10-year follow-up with a successful interview rate of 74.3% (n = 107). Clinical data was systematically retrieved each month for the first three years from the CMS and written clinical records using a standardized data entry form based on operationalized definitions. Results found shorter duration of untreated psychosis (DUP) predicted long-term clinical remission; higher educational level and shorter period of unemployment during the initial three years of the illness predicted functional recovery. Higher educational level, longer period of employment and planned medication discontinuation during the initial three years predicted complete recovery. The current study demonstrates the long-term impact of DUP and suggests improvement of employment during the early stage of illness could be a potential target for further improvement of the service., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Functional impairment is prevalent in patients with first-episode psychosis (FEP). Longitudinal course of functioning in the early stage of psychotic illness is under-studied. In this report, we aimed to investigate the patterns and baseline predictors of social-occupational functional trajectories over 3 years, utilizing growth mixture modeling (GMM) analysis, in a large representative Chinese young FEP cohort in Hong Kong., Method: Six hundred seventeen consecutive patients aged 15-25 years presenting with first-episode non-affective psychosis to a specialized early intervention service were studied. Data on demographic, pre-treatment and baseline clinical characteristics were collected. Individual class membership of functioning derived from GMM was based on ratings on Social and Occupational Functioning Scale (SOFAS) measured at five different time-points (baseline, 6, 12, 24 and 36 months) across 3-year follow-up., Results: Four distinct functional trajectories were identified including persistently poor (48.1%, n = 320), early improved (31.3%, n = 203), gradually improved (14.8%, n = 69) and improved-deteriorated (5.8%, n = 25) trajectories. Multinomial regression analysis revealed that male gender, lower educational attainment, a diagnosis of schizophrenia-spectrum disorder and a receipt of inpatient treatment upon initial presentation independently predicted persistently poor trajectory membership., Conclusion: The current study reveals a heterogeneous course of social-occupational functioning in FEP. Our finding that approximately half of the patients displaying persistently poor trajectory over 3 years indicates functional impairment as an unmet therapeutic need in early illness phase. Further research applying individual-based trajectory analysis in FEP is warranted to facilitate better characterization of longitudinal patterns of functioning and development of targeted intervention to promote early recovery., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Although physical activity helps to improve functioning and reduce the symptoms of mental illness, physical inactivity remains common in the mental illness population. This study aims to explore the associations between theoretical constructs in relation to physical activity behavior based on psychological theories to examine reasons for physical inactivity in psychosis population., Methods: One hundred and eighty one Chinese outpatients diagnosed with psychotic disorders were recruited for this cross-sectional study. Sociodemographic data and responses to questionnaires measuring self-efficacy, decisional balance, processes of change, and stages of change on physical activity habit were collected., Results: Ninety three subjects (51.4%) had the intention to engage in regular physical activity within the next six months. Significant differences were found in self-efficacy, pros of decisional balance and processes of change across the stages of change. Moreover, overall classification accuracy was 60.8% across the stages of change., Conclusions: This study supports self-efficacy, pros of decisional balance and processes of change as useful factors in understanding physical activity behavior among patients with psychosis. Future promotions of regular physical activity can focus on improving self-efficacy, emphasizing on the benefits of regular physical activity and facilitating cognitive and behavior strategies from processes of change., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Self-stigma represents a major barrier to recovery in people with psychotic disorders but is understudied in early illness stage. Longitudinal investigation of prediction for self-stigma is scarce and none is conducted in early psychosis. We aimed to prospectively examine baseline predictors of self-stigma in early psychosis patients in the context of a 3-year follow-up of a randomized-controlled trial (RCT) comparing 1-year extension of early intervention (EI) with step-down psychiatric care for first-episode psychosis (FEP)., Method: One hundred sixty Chinese patients were recruited from a specialized EI program for FEP in Hong Kong after they had completed this 2-year EI service, and underwent a 12-month RCT. Participants were followed up and reassessed 3years after inclusion to the trial. Comprehensive evaluation encompassing clinical, functional, subjective quality of life and treatment-related variables were conducted. Data analysis was based on 136 participants who completed self-stigma assessment at 3-year follow-up., Results: Fifty patients (36.8%) had moderate to high levels of self-stigma at 3-year follow-up. Multivariate regression analysis revealed that female gender, prior psychiatric hospitalization, longer duration of untreated psychosis and greater positive symptom severity at study intake independently predicted self-stigma at the end of 3-year study period., Conclusion: Our results of more than one-third of early psychosis patients experienced significant self-stigma underscore the clinical needs for early identification and intervention of self-stigmatization in the initial years of psychotic illness. Further research is warranted to clarify prediction profile and longitudinal course of self-stigma in the early illness phase., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Deficits in verbal working memory (VWM) have consistently been observed in schizophrenia, ranging from impairments in capacity, encoding, to irregular semantic organisation. However, syntactic deficits are less well-characterised, despite its crucial role in language construction. This study examines the role of simple syntactic structure (basis of the "sentence superiority effect") in VWM of patients with psychotic disorders., Methods: Patients with schizophrenia-spectrum disorders (n=40) and healthy controls matched on age, sex and education (n=40) were administered an auditory serial recall task containing word lists with low semantic coherence and either syntactically familiar structure (noun-verb-noun sequence) or syntactically unfamiliar structure. Other neurocognitive measures, symptoms and social functioning of patients were also assessed., Results: A 4-way analysis of variance (group×version×list type×serial position) indicated that patients had significantly worse performance overall, suggesting a generalised verbal memory impairment. In addition, a significant interaction was found for list type and Group, demonstrating that healthy controls, but not patients, had superior performance in syntactically familiar word lists. A subgroup analysis of high-performing patients revealed that the interaction was not an artefact of poor verbal memory, but a selective deficit in syntactic facilitation., Conclusions: Our findings may suggest segregated mechanisms for maintenance and computational aspects of VWM, and show that even simple syntactic structure facilitates recall of syntactically unfamiliar words lists. Additionally, schizophrenic patients show difficulty utilising syntactic information, which highlights the need to understand the neuropsychological basis of working memory and linguistic impairments in psychosis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Research on antipsychotic medication non-adherence in first-episode psychosis patients tends to examine non-adherence behaviors and attitudes together. Nonetheless, attitudes do not always directly translate into behaviors. We examined the baseline predictors for antipsychotics non-adherence behaviors and attitudes separately in a first-episode psychosis cohort. We also included cognitive impairments as one of the predictor variables as this domain is rarely explored in adherence studies., Method: Participants were 313 adult-onset psychosis patients recruited from the Jockey Club Early Psychosis project in Hong Kong. Demographic, premorbid, clinical, and cognitive characteristics were first assessed at baseline. Six months later, participants completed a 14-item Medication Compliance Questionnaire, which was a modified and Cantonese-translated version of the Medication Adherence Rating Scale that includes items pertaining to both adherence behaviors and attitudes., Results: Rates of poor adherence behaviors and negative adherence attitudes were 17.6% and 27.8%, respectively. Determinants of poor adherence behavior included more severe positive symptoms, hospitalization at onset of illness, and poorer engagement in extended social network. As for negative adherence attitude, determinants included more severe general psychopathology, poorer insight, more psychic medication side-effects, and poorer performance on backward digit span test and WAIS-R information test., Conclusions: The risk factors for non-adherence behaviors and attitudes are different and they should all be taken into careful consideration while formulating appropriate intervention programs to tackle the adherence problem in adult onset psychosis., (Copyright © 2016 Elsevier B.V. All rights reserved.)