Noninvasive Mapping of Striosome-Matrix Imbalance in Early Psychosis

Background: Early psychosis offers a window to identify core neurobiological disturbances before chronic illness and medication effects. The striatum, particularly its striosome and matrix compartments, plays a key role in dopaminergic and corticostriatal function. Disruption of this organization may underlie psychotic symptoms and cognitive impairment. Methods: Diffusion magnetic resonance imaging and neuropsychological data from 170 participants from the HCP-EP (Human Connectome Project for Early Psychosis) were analyzed. Using probabilistic diffusion tractography informed by animal tracer studies, the striatum was parcellated into matrix- and striosome-like voxels based on differential connectivity to cortical and subcortical targets. Group differences were assessed using analysis of covariance controlling for age, sex, medication exposure, and intracranial volume. Associations with symptom severity (Positive and Negative Syndrome Scale [PANSS]), depressive symptoms (Montgomery-Åsberg Depression Rating Scale), and cognitive performance were evaluated using covariate-adjusted partial correlations. Conclusions: Early NAP shows matrix expansion and altered striosome-matrix organization, indicating compartment-specific corticostriatal reorganization. These findings highlight a novel, noninvasive marker of striatal imbalance linked to symptoms and cognition within dopamine circuitry.