Brainwide Anatomical Connectivity and Prediction of Longitudinal Outcomes in Antipsychotic-Naïve First-Episode Psychosis.

Background: Disruptions 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 remain unknown.

Methods: We acquired diffusion-weighted magnetic resonance images to map structural connectivity between each pair of 319 parcellated brain regions in 61 antipsychotic-naïve individuals with first-episode psychosis (15-25 years, 46% female) and a demographically matched sample of 27 control participants. Clinical follow-up data were also acquired in patients 3 and 12 months after the scan. We used connectome-wide analyses to map disruptions of inter-regional pairwise connectivity and connectome-based predictive modeling to predict longitudinal change in symptoms and functioning.

Results: Individuals with first-episode psychosis showed disrupted connectivity in a brainwide network linking all brain regions compared with controls (familywise error-corrected p = .03). Baseline structural connectivity significantly predicted change in functioning over 12 months (r = 0.44, familywise error-corrected p = .041), such that lower connectivity within fronto-striato-thalamic systems predicted worse functional outcomes.

Conclusions: Brainwide 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 1 year after engagement with treatment services.