Brain-wide Disruptions of Anatomical Connectivity in Antipsychotic-Naive First Episode Psychosis

OBJECTIVEDisruptions of axonal connectivity are thought to be a core pathophysiological feature of psychotic illness, but whether they are present early in the illness, prior to antipsychotic exposure, and whether they can predict clinical outcome remains unknown. METHODSWe acquired diffusion-weighted MRI to map axonal connectivity between each pair of 319 parcellated brain regions in 61 antipsychotic-naive individuals with First Episode Psychosis (FEP; 15-25 years, 46% female) and a demographically matched sample of 27 control participants, along with clinical follow-up data in patients 3 months and 12 months after the scan. We used connectome-wide analyses to map disruptions of inter-regional pairwise connectivity coupled with connectome-based predictive modelling to predict longitudinal change in symptoms and functioning. RESULTSIndividuals with FEP showed disrupted connectivity in a brain-wide network linking all brain regions when compared with controls (pFWE = .03). Baseline structural connectivity significantly predicted change in functioning over 12 months (r = .44; pFWE = .041), such that lower connectivity within fronto- striato-thalamic systems predicted worse functional outcomes. CONCLUSIONSBrain-wide reductions of structural connectivity exist during the early stages of psychotic illness and cannot be attributed to antipsychotic medication. Moreover, baseline measures of structural connectivity can predict change in patient functional outcomes up to one year after engagement with treatment services.