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Brain Morphology of Cannabis Users With or Without Psychosis: A Pilot MRI Study

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Risperidone reduces individualized morphometric similarity deviation in schizophrenia and associates with cortical

Liju Liu^1,2, Mi Yang^3,4, Jinxing Chen^1,2

¹The Clinical Hospital of Chengdu Brain Science Institute, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, PR China.

Schizophrenia (Heidelberg, Germany)

|January 9, 2026

Summary

Risperidone treatment in schizophrenia patients reduced deviations in cortical morphometric similarity (MSD), aligning with normative patterns. These structural changes correlate with gene expression linked to neurotransmission and immune functions, suggesting a molecular basis for treatment benefits.

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Area of Science:

Neuroscience
Genetics
Psychiatry

Background:

Schizophrenia is associated with reduced cortical thickness and altered gene expression.
Antipsychotic treatment impacts cortical morphology and gene expression, but its effect on individual morphometric similarity and genetic mechanisms is unclear.

Purpose of the Study:

To quantify risperidone-induced changes in individual morphometric similarity.
To investigate the spatial alignment of these changes with cortical transcriptomic patterns.

Main Methods:

T1-weighted imaging in 24 drug-naive first-episode schizophrenia patients and 30 controls.
Cortical morphometric similarity matrices calculated using Wasserstein distance; Morphometric Similarity Deviation (MSD) defined.
Partial least squares regression linked MSD changes to Allen Human Brain Atlas transcriptomic data.

Main Results:

Patients showed high baseline MSD in frontal, temporal, and temporoparietal regions, linked to symptom severity.
Risperidone treatment decreased MSD, particularly in the salience/ventral attention network, correlating with improved emotional intelligence.
Treatment-induced MSD changes spatially correlated with genes in neurotransmission, cell adhesion, and immune function, expressed in astrocytes and oligodendrocytes.

Conclusions:

Risperidone normalizes cortical morphometric similarity towards a healthy pattern.
These structural normalization effects are linked to gene expression patterns, particularly in neurotransmission and immune processes.
This suggests a molecular basis for the structural and cognitive benefits of risperidone treatment in schizophrenia.