Antipsychotics cause reversible structural brain changes within one week

Determining the effects of antipsychotics on MRI brain structural metrics without the potential confounding effects related to the natural course of a psychotic illness is challenging. However, it is crucial to understand these effects to interpret the results of cross-sectional and longitudinal studies in medicated patients and, ultimately, to understand better the biological mechanisms driving antipsychotics' effects. In this work, we aim to determine whether exposure to antipsychotics is associated with alterations in brain MRI structural metrics in the absence of disease effects. A randomized, double-blind, counter-balanced order, crossover, placebo-controlled study in healthy volunteers was performed. The study comprised two arms. Within arms, participants were randomized to receive daily doses of either the active compound (Arm 1= amisulpride 400 mg/day, N = 24; Arm 2= aripiprazole 10 mg/day, N = 24) for one week, followed by placebo or vice versa. We found increased MRI volume estimates in the left putamen and in the right caudate in the amisulpride condition as compared to placebo and increased right putamen volume estimates after aripiprazole compared to placebo. No other effects were found in cortical volume estimates, cortical thickness, cortical surface area, and T1-relaxation time. Striatal changes reversed within weeks of drug withdrawal. Short-term exposure to either one of two different antipsychotics results in a transient increase in striatal volume measured with T1-weighted MRI that normalizes rapidly on stopping treatment without cortical changes. Our findings suggest that striatal volumetric MRI differences detected in people with schizophrenia taking antipsychotics are, at least in part, attributable to pharmacological effects.