Trajectories of psychotic symptoms and fronto-parietal resting state functional connectivity MRI following an antipsychotic trial in medication-naïve first-episode psychosis patients

Evidence of heterogeneity in the trajectory of psychosis is abundant. Here, we applied group-based trajectory modeling on positive symptoms and collected resting state fMRI data of 81 medication-naïve first episode psychosis (FEP) patients during a 16-week antipsychotic drug (APD) trial. Data from 131 healthy controls (HCs) were also acquired during the trial for comparison. Three major trajectory subgroups were identified and labeled as Fast (50.6%), Delay (35.8%), and Partial responders (13.6%). Logistic regressions revealed that Fast responders (vs. Partial) showed significantly lower psychopathology symptoms prior to treatment and lower APD dosage after the trial. Moreover, Delay responders showed significant increases in executive control network resting state functional connectivity (ECN FC) during the trial towards a normalization (using HCs as reference), while Fast and Partial responders to a lesser extent. These changes were associated with treatment response (reduction in positive symptoms after the trial). Future work should harness the potential of ECN FC to inform the mechanism of delayed responses with the potential to start unraveling psychotic heterogeneity which has hampered our ability to identify new treatment strategies and lead to better clinical outcomes. (Clinical trial registration: Trajectories of Treatment Response as Window into the Heterogeneity of Psychosis: A Longitudinal Multimodal Imaging Study, NCT03442101 https://clinicaltrials.gov/ct2/show/NCT03442101 . Glutamate, Brain Connectivity and Duration of Untreated Psychosis (DUP), NCT02034253 https://clinicaltrials.gov/ct2/show/NCT02034253 ).