Clinical and Neurobiological Characterization of Akathisia in Schizophrenia Spectrum Disorders and Mood Disorders

Akathisia is a severe psychomotor syndrome characterized by distressing subjective restlessness and observable repetitive, purposeless movements. Despite its substantial clinical impact, it remains underrecognized, and its neurobiological underpinnings are poorly understood. In this study, we examined clinical, cognitive, psychomotor, and structural brain correlates of akathisia across schizophrenia spectrum disorders (SSD) and mood disorders (MOD).

A total of 308 patients (SSD: n = 215, MOD: n = 93) underwent structural magnetic resonance imaging (MRI) and deep clinical phenotyping. Akathisia was assessed using the Barnes Akathisia Rating Scale. In addition, different scales were used to assess psychopathology, global and cognitive functioning, and other psychomotor abnormalities. Structural 3T MRI data were processed using FreeSurfer version 7.4.1.

Akathisia prevalence was 21.9% in SSD and 12.9% in MOD. In SSD, akathisia was associated with younger age, poorer global functioning, greater psychopathology, and more pronounced psychomotor abnormalities. In MOD, akathisia was linked to higher psychopathology and poorer cognitive performance. Neurobiologically, SSD patients with akathisia showed reduced cortical thickness in the paracentral lobule, primary motor cortex, and superior frontal gyrus, without differences in cortical surface area or basal ganglia structures. No structural MRI differences were observed in MOD.

As the largest transdiagnostic structural MRI study of akathisia to date, our findings support its characterization as a distinct clinical and neurobiological phenotype, particularly in SSD.