Noninvasive Mapping of Striosome-Matrix Imbalance in Early Psychosis.

Overview

1. Psychotic Disorders Division, McLean Hospital, Belmont, Massachusetts
2. McLean Imaging Center, McLean Hospital, Belmont, Massachusetts
3. Harvard Medical School, Boston, Massachusetts
4. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts
5. Division of Pediatric Neurology, Department of Pediatrics, University of Texas Southwestern, Dallas, Texas
6. Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California

Abstract

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.

Results: Individuals with nonaffective psychosis (NAP) showed significantly larger left matrix-like volume compared with control participants (q = .001), with affective psychosis participants demonstrating intermediate values. No significant differences were observed in striosome-like volumes. Spatial analyses revealed posterior and inferior displacement of striosomal centers and increased striosome–matrix separation in NAP. Higher PANSS scores were associated with reduced right striosome-like and increased right matrix-like volumes (q < .05), while better cognitive performance correlated with greater striosome-like and lower matrix-like volumes bilaterally.

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.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

• humanconnectome.org/study/human-connectome-project-for-early-psychosis, at Human Connectome Project; found in the text, “Data Collection”

Versions

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Version 2, 28 September 2026

• Authors: added Akila Weerasekera (0000-0003-0446-7604); removed Akila Weerasekera

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 6 authors, 5 keywords, 1 funder, 53 references.

Cite

This paper

Weerasekera, A., Waugh, J. L., Öngür, D., Nolan, G. P., Mody, M., & Du, F. (2026). Noninvasive Mapping of Striosome-Matrix Imbalance in Early Psychosis. Biological psychiatry global open science, 6(5), 100785. https://doi.org/10.1016/j.bpsgos.2026.100785

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