The Effects of Antipsychotics on Two Month Cortical Thickness and Two Year Clinical Outcomes Among Populations at Clinical High Risk for Psychosis

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BACKGROUND AND HYPOTHESIS: Antipsychotics (APs) are often used among individuals with clinical high risk (CHR) for psychosis and affect cortical thickness (CT). Whether clinical and CT changes after initial AP use correlate with long-term clinical outcomes remains largely unknown. STUDY DESIGN: One hundred and thirty-eight CHRs and 65 healthy controls accepted 2 MRI scans at an interval of 2 months. CHRs were categorized as responders (n = 53) and non-responders (n = 69) based on their response to APs after 2-month treatment. According to 2-year outcomes, they were also subdivided into converters (n = 26) and non-converters (n = 96). The relationships among short-term CT changes, AP effects, and long-term outcomes were explored. STUDY RESULTS: At baseline, CHRs had CT reduction in the right inferior temporal cortex with a correlation with clinical symptoms. At 2 month, CHRs showed steeper gray matter loss in bilateral frontotemporal regions than healthy controls. Cortical thickness change rates of the clusters located in bilateral middle temporal and right lateral orbitofrontal cortex were negatively correlated with the cumulative AP dose. Furthermore, 2-year psychosis conversion rate was significantly higher in non-responders than responders (33.3% vs 5.1%). A random forest model based on demographic, clinical, baseline, and longitudinal CT variables predicted 2-year conversion with an AUC of 0.90 (accuracy: 0.83, sensitivity: 0.78, and specificity: 0.89), with model predictive power driven primarily by symptom and CT variables. CONCLUSIONS: These findings contribute valuable insights into the potential impact of early AP treatment on brain morphology and clinical trajectories and highlight the importance of monitoring the initial treatment responses.

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