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Mentalizing, or theory of mind (ToM), impairments and self-referential hypermentalizing bias are well-evident in schizophrenia. However, findings compared to individuals with at-risk mental states (ARMS) are inconsistent, and investigations into the relationship between social cognitive impairments and social anxiety in the two populations are scarce. This study aimed to examine and compare these deficits in first-episode schizophrenia-spectrum disorder (FES) and ARMS, and to explore potential specific associations with neurocognition and symptomatology. Forty patients with FES, 40 individuals with ARMS, and 40 healthy controls (HC) completed clinical assessments, a battery of neurocognitive tasks, and three social cognitive tasks. The comic strip and hinting tasks were used to measure non-verbal and verbal mentalizing abilities, and the gaze perception task was employed to assess self-referential hypermentalizing bias. FES and ARMS showed comparable mentalizing impairments and self-referential hypermentalizing bias compared to HC. However, only ambiguous self-referential gaze perception (SRGP) bias remained significantly different between three groups after controlling for covariates. Findings suggested that self-referential hypermentalizing bias could be a specific deficit and may be considered a potential behavioral indicator in early-stage and prodromal psychosis. Moreover, working memory and social anxiety were related to the social cognitive impairments in ARMS, whereas higher-order executive functions and positive symptoms were associated with the impairments in FES. The current study indicates the presence of stage-specific mechanisms of mentalizing impairments and self-referential hypermentalizing bias, providing insights into the importance of personalized interventions to improve specific neurocognitive domains, social cognition, and clinical outcomes for FES and ARMS., (© 2024. The Author(s).)

Background: Metabolic syndrome (MetS) is common following first-episode psychosis (FEP), contributing to substantial morbidity and mortality. The Psychosis Metabolic Risk Calculator (PsyMetRiC), a risk prediction algorithm for MetS following a FEP diagnosis, was developed in the United Kingdom and has been validated in other European populations. However, the predictive accuracy of PsyMetRiC in Chinese populations is unknown., Methods: FEP patients aged 15-35 y, first presented to the Early Assessment Service for Young People with Early Psychosis (EASY) Programme in Hong Kong (HK) between 2012 and 2021 were included. A binary MetS outcome was determined based on the latest available follow-up clinical information between 1 and 12 years after baseline assessment. The PsyMetRiC Full and Partial algorithms were assessed for discrimination, calibration and clinical utility in the HK sample, and logistic calibration was conducted to account for population differences. Sensitivity analysis was performed in patients aged >35 years and using Chinese MetS criteria., Findings: The main analysis included 416 FEP patients (mean age = 23.8 y, male sex = 40.4%, 22.4% MetS prevalence at follow-up). PsyMetRiC showed adequate discriminative performance (full-model C = 0.76, 95% C.I. = 0.69-0.81; partial-model: C = 0.73, 95% C.I. = 0.65-0.8). Systematic risk underestimation in both models was corrected using logistic calibration to refine PsyMetRiC for HK Chinese FEP population (PsyMetRiC-HK). PsyMetRiC-HK provided a greater net benefit than competing strategies. Results remained robust with a Chinese MetS definition, but worse for the older age group., Interpretation: With good predictive performance for incident MetS, PsyMetRiC-HK presents a step forward for personalized preventative strategies of cardiometabolic morbidity and mortality in young Hong Kong Chinese FEP patients., Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., Competing Interests: RU is supported by the NIHR Oxford Health Biomedical Research Centre. The views expressed are those of the author and not necessarily those of the NIHR or the Department of Health and Social Care. RU has received speaker fee at non promotional educational event for Otsuka June 2022, paid consultancy for Vitaris July 2022 and for Springer Healthcare December 2021. SKWC received research funding from the Health and Medical Research Fund and General Research Fund of Hong Kong. HL received research funding from the General Research Fund of Hong Kong., (© 2024 The Author(s).)

Mentalizing impairment is one of the core features of schizophrenia, and bias judgement of others' gaze as self-directing is common to schizophrenia patients. In this case-control study, 30 patients with first-episode schizophrenia (FES) and 30 matched healthy controls were assigned gaze perception tasks with variable stimulus presentation times (300 ms and no time limit) to determine the presence of self-referential gaze perception (SRGP) bias. The eye movement pattern during the task were tracked and data were analysed using hidden Markov models (HMMs). The SRGP involves reporting of others' gaze intent and was used as a measurement of explicit mentalizing process. Eye movement measurement represents automated visual attention pattern and was considered as a measurement of implicit mentalizing process. The patients with FES had significantly more SRGP bias than the controls in the 300 ms condition but not in the no-time-limit condition. Social cognitive function was related to SRGP bias in the patient group. Two distinct eye movement patterns were identified: eye-focused and nose-focused. Significant group differences in eye movement patterns in the 300 ms condition were found with more controls had eye-focused pattern. Social anxiety symptoms were related to the nose-focused pattern, positive psychotic symptoms were related to the eye-focused pattern, and depressive symptoms were related to less consistent eye movement patterns. No significant relationship was found between SRGP bias and eye movement patterns. The dissociation between explicit and implicit mentalizing processes with different cognitive and symptom dimensions associated with the two processes suggests the presence of different mechanisms., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Aim: Sex differences are well documented in schizophrenia, but have been much less studied in at-risk mental state (ARMS) for psychosis. We aimed to examine sex differences in symptomatology, cognition, social and role functioning in individuals with ARMS, with specific focus on clarifying relationships between sex, negative symptoms and functioning., Methods: One hundred and seventy-seven Chinese participants aged 15-40 years with ARMS were recruited from a specialized early intervention service in Hong Kong. ARMS status was verified by Comprehensive Assessment of At-Risk Mental State. Assessments encompassing symptom profiles, a brief battery of cognitive tests and social and role functioning were conducted. Brief Negative Symptom Scale was adapted to measure negative symptoms at the level of five core domains., Results: Males with ARMS exhibited significantly poorer social functioning and more severe asociality of negative symptoms than female counterparts. Mediation analysis revealed that sex difference in social functioning became statistically insignificant when asocality was included in the model, indicating that asociality mediated the relationship between sex and social functioning. No sex differences were observed in other core domains of negative symptoms, other symptom dimensions, cognitive measures and role functioning., Conclusions: This study suggests that sex differences in ARMS may be less pronounced that those observed in established psychotic disorders. Our findings of differential pattern of asociality between sexes and its mediating role on sex difference in social functioning underscore the importance in investigating negative symptoms at a separable domain-level. Further research is required to identify sex-specific predictors of longitudinal outcomes in at-risk populations., (© 2021 John Wiley & Sons Australia, Ltd.)

Aim: Psychiatric comorbidity frequently occurs with at-risk mental state (ARMS) for psychosis. Its relationships with psychopathology, cognition and functioning, however, remain to be further clarified. We aimed to examine prevalence and correlates of psychiatric comorbidity, and its associations with psychosocial functioning and subjective quality-of-life (QoL) in a representative sample of Chinese ARMS individuals., Methods: One hundred ten help-seeking participants aged 15 to 40 years with ARMS were recruited from a specialized early psychosis service in Hong Kong. ARMS status was verified by comprehensive assessment of at-risk mental state (CAARMS). Comorbid Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition non-psychotic psychiatric disorders at baseline were ascertained using diagnostic interview and medical record review. Assessments encompassing symptom profiles, psychosocial functioning, subjective QoL and a brief cognitive battery were conducted., Results: Forty-nine (44.5%) ARMS participants were diagnosed as having comorbid non-psychotic psychiatric disorders at baseline, primarily depressive and anxiety disorders. Binary multiple logistic regression analysis revealed that female gender, more severe depressive symptoms, higher suicidality and poorer global cognitive functioning were independently associated with comorbid diagnosis status. ARMS participants with psychiatric comorbidity displayed significantly more limited extended social networks and poorer subjective QoL than those without psychiatric comorbidity., Conclusion: Comorbid disorders were frequently observed in Chinese ARMS individuals, and were linked to poorer cognition and higher suicide risk. Our findings underscore a potential critical role of psychiatric comorbidity in determining social functioning and subjective QoL in at-risk individuals. Further longitudinal research is required to clarify trajectories of comorbid disorder status and its prospective impact on clinical and functional outcomes in ARMS populations., (© 2020 John Wiley & Sons Australia, Ltd.)

Background: To explore the prevalence and clinicians' awareness of psychiatric comorbidities, and to identify factors associated with current psychiatric comorbidities in first-episode schizophrenia (FES) patients., Method: In this cross-sectional study, 128 patients with FES, who were in symptomatic remission, were consecutively recruited from a local early intervention clinic. All patients were interviewed using the Chinese bilingual version of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Axis I Disorders, Positive and Negative Syndrome Scales, Scale to Assess Unawareness of Mental Disorder, Social and Occupational Functioning Assessment Scale, Simpson-Angus Scale, Barnes Akathisia Rating Scale and Abnormal Involuntary Movement Scale. Bivariate and multivariate analyses were performed to investigate factors associated with psychiatric comorbidities in FES patients., Results: The lifetime and point prevalence of psychiatric comorbidities among FES patients were 47.7% and 27.3%, respectively. Current psychiatric comorbidities were documented on the medical records of 39.3% of the patients. The FES patients with current psychiatric comorbidities had a lower level of functioning. Depression in FES was also associated with akathisia., Conclusion: Psychiatric comorbidities are prevalent among community FES patients. In addition to achieving symptomatic remission in schizophrenia, both treating psychiatric comorbidities and minimizing the side-effects of treatment, particularly akathisia, are fundamental for supporting FES patients in their journey to recovery., (© 2017 John Wiley & Sons Australia, Ltd.)

Aim: To explore the changes of functioning in people suffering from first-episode psychosis throughout their first year into an early intervention service, and the baseline predictors of their functioning levels at baseline, 6 and 12 months METHOD: Consecutive subjects presenting to an early intervention service were recruited from 1 February 2013 to 31 May 2015. Information on their socio-demographic status was collected. Structured instruments were used to assess their premorbid functioning, duration of untreated psychosis, psychopathology and insight at baseline. Psychosocial functioning was assessed by Social Occupational Functioning Assessment Scale (SOFAS) and Role Functioning Scale at baseline, 6 and 12 months., Results: A total of 269 subjects were recruited. The mean baseline scores for SOFAS were 53.1 (standard deviation = 13.6) and 21.5 (standard deviation = 4.0), respectively. Positive and negative psychopathology, insight and mode of onset were significant factors associated with baseline functioning. Functioning by both instruments showed significant improvement after 6 months, and the gains were maintained at 12 months. For SOFAS, baseline insight (P = 0.008), education attainment (P = 0.016) and its own baseline score (P = 0.024) were predictive at 6 months, while for 12 months, only education attainment was predictive (P = 0.008). For Role Functioning Scale, its baseline score (P = 0.034) was predictive at 6 months, while at 12 months, only female gender predicted better role functioning., Conclusion: Factors predictive of functioning levels at the three time points were different. Phase-specific intervention should be offered to enhance functional recovery of people with first-episode psychosis., (© 2016 John Wiley & Sons Australia, Ltd.)

Background: Risks of neurological deterioration after heparin administration following cervical spinal cord injury (SCI) in humans are unknown., Objective: To elucidate the safety of heparin following cervical SCI and investigate its potential neuroprotectant role., Methods: Sixty-two Sprague Dawley adult rats were subjected to mild (0.6 mm), moderate (0.9 mm), or severe (1.2 mm) C7-SCI. At each injury severity, intravenous heparin or saline was administered for 72 hours following SCI. Behavioral tests (Basso, Beattie, Bresnahan scores, Hargreave's) were performed before killing the rats at week 7. Half of the rats were killed at day 3, and the remainder at week 7 after SCI. Immunohistochemistry, Western blot analysis, and axonal retrograde tracing were conducted at both times., Results: Subpial hemorrhage was greater in heparin-treated animals compared with controls at all severities of SCI day 3 after injury. Counterintuitively, intraparencyhmal hemorrhage was minimal in the lesion epicenter following mild SCI in the heparin-treated animals compared with controls. India ink perfusion revealed greater preservation of microcirculation in heparin-treated animals compared with a reduction in control animals. A decrease in spinal cord perfusion correlated directly with an increase in hypoxia-inducible factor-1α expression. There was significant gray matter sparing, but no change in white matter volume after heparin treatment at week 7 in the mild SCI group. Beneficial effects on hemorrhagic volume, axon sparing, and functional recovery following heparin treatment were not observed in the moderate or severe SCI group., Conclusion: Heparin treatment following SCI is safe at all degrees of injury. Heparin decreases platelet aggregation and microvascular occlusion, providing a potential neuroprotective effect following mild SCI.