Modeling the effects of treatment resistance and anticholinergic burden on cognitive function domains in patients with schizophrenia.

The contribution of anticholinergic burden to cognitive function in patients with treatment resistant schizophrenia (TRS) is uncertain. This case-control study aims to comprehensively examine the association between treatment resistance and cognitive functions and the contribution of anticholinergic burden in patients with schizophrenia. Anticholinergic burden of all patients was calculated using the Anticholinergic Cognitive Burden scale. Exploratory Factor Analysis of 11 cognitive assessments identified four cognitive domains: verbal memory, attention and general cognitive functions, visual memory and processing speed, and executive function. Two structural equation models (SEM) examined the relationship of TRS and these cognitive functions with, and without considering anticholinergic burden. A total of 288 participants were included (TRS N=111, non-TRS N=177). Patients with TRS performed poorer than the non-TRS group only in the executive function domain. Anticholinergic burden contributed significantly to the attention and general cognitive functions, visual memory and processing speed, and executive function. The impact of TRS on executive function was no longer significant after adding anticholinergic burden to the SEM. Results suggested that anticholinergic burden contributes to a wide range of cognitive function impairment in patients with schizophrenia and is likely to be part of the apparent differences of cognitive function between TRS and non-TRS.

Sex differences in symptom severity, cognition and psychosocial functioning among individuals with at-risk mental state for psychosis.

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.

Psychiatric comorbidity in individuals at-risk for psychosis: Relationships with symptoms, cognition and psychosocial functioning.

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.