Exploring white matter microstructure and the impact of antipsychotics in adolescent-onset psychosis.

Claudia Barth,Ole A Andreassen,Tiril Pedersen Gurholt,Ingrid Agartz,Anne M Myhre,Vera Lonning,Joseph Najbauer

doi:10.1371/journal.pone.0233684

Abstract

White matter abnormalities are well-established in adult patients with psychosis. Less is known about abnormalities in the rarely occurring adolescent early onset psychosis (EOP). In particular, whether antipsychotic medication might impact white matter microstructure is not known. Using 3T diffusion weighted imaging, we investigated differences in white matter microstructure and the impact of antipsychotic medication status in medicated (n = 11) and unmedicated (n = 11) EOP patients relative to healthy controls (n = 33), aged between 12-18 years. 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 in patients. We found significantly lower FA in the left genu of the corpus callosum, the left anterior corona radiata (ACR) and the right superior longitudinal fasciculus in EOP patients relative to healthy controls. AD values were also lower in the left ACR, largely overlapping with the FA findings. Mean FA in the left ACR was significantly associated with antipsychotic medication status (Cohen's d = 1.37, 95% CI [0.01, 2.68], p = 0.008), 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 hypothesized to contribute to the etiology of psychosis. Replications are warranted to draw firm conclusions about putatively enhancing effects of antipsychotic medication on white matter microstructure in adolescent-onset psychosis.

Highlights

Psychotic disorders such as schizophrenia typically emerge during late adolescence or early adulthood, with debilitating consequences
Sample demographics and clinical characteristics separated by antipsychotic medication status of early onset psychosis (EOP) patients are reported in Table 1 and Table 2, respectively
EOP patients did not differ significantly from controls in general demographic variables such as age, handedness and intelligence quotient (IQ) (Table 1). In line with their clinical diagnosis, EOP patients showed higher impairment of general functioning evaluated with CGAS and exhibited significantly more depressive symptoms assessed with MFQ, relative to their healthy counterparts

Summary

Introduction

Psychotic disorders such as schizophrenia typically emerge during late adolescence or early adulthood, with debilitating consequences. While white matter microstructural alterations are well-established in adult onset psychosis [5], less is known about putative alterations in adolescent EOP. Studies investigating white matter microstructure in EOP mainly focus on case-control differences, either reporting antipsychotic effects as secondary findings or using antipsychotic medication status as a covariate of no interest. Studies in EOP patients do not indicate an impact of either current [18,19,20] or cumulative antipsychotic exposure [12, 19, 21] on regional scalar DWI measures. Zeroing in on unmedicated relative to medicated EOP patients provides the opportunity to investigate the impact of antipsychotic medication on white matter microstructure early in disease progression. As there are no established effects of antipsychotic medication on white matter microstructure in EOP patients, our post hoc analyses are exploratory by nature

Participants

Results

Discussion