Impact of second-generation antipsychotics on white matter microstructure in adolescent-onset psychosis

Abstract White matter abnormalities are well-established in adult patients with psychosis. Yet less is known about changes in early onset psychosis (EOP) during adolescence, especially whether antipsychotic medication might impact white matter microstructure in this sensitive phase. Here, we utilized Magnetic Resonance Imaging (MRI) in unmedicated and medicated adolescent EOP patients in comparison to healthy controls to examine the impact of antipsychotic medication status on indices of white matter microstructure. Twenty-two EOP patients (11 unmedicated) and 33 healthy controls, aged between 12-18 years, underwent 3T diffusion-weighted MRI. Using Tract-based Spatial Statistics, we calculate case-control differences in scalar diffusion measures, i.e. fractional anisotropy (FA), axial diffusion (AD) and radial diffusion (RD), and investigated their association with antipsychotic medication. We found significantly lower mean FA and AD in largely overlapping areas, particularly in left anterior corona radiata (ACR), in EOP patients relative to healthy controls. Mean FA in the left ACR was significantly associated with antipsychotic medication status (t = 2.991, p = 0.008, R 2 = 0.298), showing higher FA values in medicated compared to unmedicated EOP patients. The present study is the first to link antipsychotic medication status to altered regional FA in the left ACR, a region being discussed to contribute to the etiology of psychosis. Yet, further work with larger samples is needed to draw firm conclusions about putatively enhancing effects of antipsychotic medication on white matter microstructure early in the disease process.