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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.

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.

BACKGROUND: Reinforcement learning (RL) impairment has been observed in chronic schizophrenia and first-episode psychosis. Yet, there is a paucity of research of RL impairment in individuals at clinical high-risk (CHR) for psychosis. The current study aimed to examine RL performance in a representative cohort of Chinese CHR subjects, with particular focus on its relationship with primary negative symptoms (PNS). METHODS: Ninety-seven Chinese individuals with CHR for psychosis, aged 15–40 years, were recruited from a territory-wide specialized early intervention service for psychosis in Hong Kong. CHR status was verified using Comprehensive Assessment of At-Risk Mental State (CAARMS). Thirty-four demographically-matched healthy controls were recruited as a comparison group. Each subject completed two computerized RL tasks (Go-No-Go, GNG and Gains-Loss Avoidance GLA tasks) which have been studied in chronic and first-episode schizophrenia patients. In both tasks, rapid / gradual and positive / negative RL measures were derived for analyses. CHR subjects were categorized as having PNS if they had (1) global score ≥ 3 on at least two of the following SANS subscales: Affective flattening, Alogia, Avolition-apathy or Anhednoia-asociality; and (2) no or clinically non-significant depression with total score < 16 in Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: On GNG task, three-group comparison (PNS, non-PNS, control groups) revealed significant difference in RL accuracy, with post-hoc contrasts showing that controls performed better than both PNS and non-PNS groups in gradual positive RL. No between-group difference in Go-response bias or rapid learning was observed. On GLA task, main effect of group was noted in three-group comparison analysis on RL accuracy. Post-hoc tests indicated that PNS group displayed significantly lower accuracy than both non-PNS group and controls in gradual positive and negative RL. Additionally, PNS group exhibited significantly lower overall and block-1 win-stay rates than controls. DISCUSSION: Our results indicate RL impairment in CHR sample. In particular, such RL impairment was more evident in CHR subjects presenting with PNS relative to those without PNS. Further investigation is required to verify and confirm our findings on the relationship between negative symptoms and RL deficits. In addition, a prospective follow-up of our CHR cohort will help clarify the potential utility of baseline RL impairment in enhancing prediction of psychosis transition at follow-up.

Background Neurocognitive impairment is a core feature of schizophrenia, and has been observed among healthy non-psychotic siblings of schizophrenia patients as well as individuals at clinical high-risk (CHR) for psychosis. Thus far, few studies have directly contrasted neurocognitive performance between non-psychotic siblings and CHR samples. Potential differential patterns of neurocognitive deficits among schizophrenia patients, familial high-risk and CHR samples remain to be clarified. This study aimed to compare neurocognitive functions among first-episode schizophrenia (FES) patients, their non-psychotic siblings, CHR individuals, and healthy controls. Methods FES patients (n=69, mean age=25.3) and CHR individuals (n=97, mean age=21.1) without family history of psychosis were recruited from a territory-wide specialized early intervention service for psychosis in Hong Kong. A group of non-psychotic siblings of FES patients (n=50, mean age=25.4) and healthy controls (HC) (n=68, mean age=24.5) were also recruited. A standardized battery of neurocognitive tests encompassing working memory, processing speed, executive function, visual memory, verbal learning, and sustained attention was administered. Group differences were examined using analysis of covariance (ACOVA) with Bonferroni correction applied for statistical significance (P

The expansion of a hexanucleotide (GGGGCC) repeat in C9ORF72 is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Both the function of C9ORF72 and the mechanism by which the repeat expansion drives neuropathology are unknown. To examine whether C9ORF72 haploinsufficiency induces neurological disease, we created a C9orf72-deficient mouse line. Null mice developed a robust immune phenotype characterized by myeloid expansion, T cell activation and increased plasma cells. Mice also presented with elevated autoantibodies and evidence of immune-mediated glomerulonephropathy. Collectively, our data suggest that C9orf72 regulates immune homeostasis and an autoimmune response reminiscent of systemic lupus erythematosus (SLE) occurs in its absence. We further imply that haploinsufficiency is unlikely to be the causative factor in C9ALS/FTD pathology.