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Background.Individuals identified as at ultra-high risk (UHR) for psychosis are at risk of poor functional outcome regardless of development of psychotic disorder. Studies examining longitudinal predictors of poor functioning have tended to be small and report only medium-term follow-up data. We sought to examine clinical predictors of functional outcome in a long-term longitudinal study.Method.Participants were 268 (152 females, 116 males) individuals identified as UHR 2–14 years previously. A range of clinical and sociodemographic variables were assessed at baseline. Functioning at follow-up was assessed using the Social and Occupational Functioning Assessment Scale (SOFAS).Results.Baseline negative symptoms, impaired emotional functioning, disorders of thought content, low functioning, past substance use disorder and history of childhood maltreatment predicted poor functioning at follow-up in univariate analyses. Only childhood maltreatment remained significant in the multivariate analysis (p < 0.001). Transition to psychosis was also significantly associated with poor functioning at long-term follow-up [mean SOFAS score 59.12 (s.d. = 18.54) in the transitioned group compared to 70.89 (s.d. = 14.00) in the non-transitioned group, p < 0.001]. Childhood maltreatment was a significant predictor of poor functioning in both the transitioned and non-transitioned groups.Conclusions.Childhood maltreatment and transition to psychotic disorder independently predicted poor long-term functioning. This suggests that it is important to assess history of childhood maltreatment in clinical management of UHR individuals. The finding that transition to psychosis predicts poor long-term functioning strengthens the evidence that the UHR criteria detect a subgroup at risk for schizophrenia. [ABSTRACT FROM PUBLISHER]

BackgroundWhether there are differential effects of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) on the brain is currently debated. Although some studies report that FGAs reduce grey matter more than SGAs, others do not, and research to date is limited by a focus on schizophrenia spectrum disorders. To address this limitation, this study investigated the effects of medication in patients being treated for first-episode schizophrenia or affective psychoses.MethodCortical thickness was compared between 52 first-episode psychosis patients separated into diagnostic (i.e. schizophrenia or affective psychosis) and medication (i.e. FGA and SGA) subgroups. Patients in each group were also compared to age- and sex-matched healthy controls (n = 28). A whole-brain cortical thickness interaction analysis of medication and diagnosis was then performed. Correlations between cortical thickness with antipsychotic dose and psychotic symptoms were examined.ResultsThe effects of medication and diagnosis did not interact, suggesting independent effects. Compared with controls, diagnostic differences were found in frontal, parietal and temporal regions. Decreased thickness in FGA-treated versus SGA-treated groups was found in a large frontoparietal region (p < 0.001, corrected). Comparisons with healthy controls revealed decreased cortical thickness in the FGA group whereas the SGA group showed increases in addition to decreases. In FGA-treated patients cortical thinning was associated with higher negative symptoms whereas increased cortical thickness in the SGA-treated group was associated with lower positive symptoms.ConclusionsOur results suggest that FGA and SGA treatments have divergent effects on cortical thickness during the first episode of psychosis that are independent from changes due to illness. [ABSTRACT FROM PUBLISHER]