# Distinct subcortical neuroanatomic profiles of treatment-resistant schizophrenia: structural magnetic resonance imaging study

## TL;DR

This study finds that different brain structures are linked to treatment response in schizophrenia, showing that brain anatomy varies between treatment-resistant and treatment-responsive patients.

## Contribution

The study identifies distinct subcortical neuroanatomic profiles associated with treatment response subgroups in schizophrenia.

## Key findings

- Treatment-resistant patients showed reduced nucleus accumbens and enlarged lateral ventricles.
- FLR patients had larger pallidal volumes and more focal hippocampal subfield reductions.
- Hippocampal and amygdala volumes were smaller in all schizophrenia subgroups compared to controls.

## Abstract

Understanding the neuroanatomical correlates of treatment response in schizophrenia is crucial for improving clinical stratification and clarifying underlying pathophysiological mechanisms.

To examine subcortical volumetric differences across clinically defined schizophrenia treatment-response subgroups.

T1-weighted structural magnetic resonance imaging data were analysed from 109 participants, including 79 individuals with schizophrenia and 30 healthy controls. Patients were categorised into three distinct treatment response groups: ultra-treatment-resistant (UTR; n = 22), clozapine-responsive (n = 28) and first-line antipsychotic responsive (FLR; n = 29). Group differences were examined across 33 regions of interest, including subcortical, ventricular and hippocampal subfield regions.

The UTR group had higher antipsychotic dosages and exhibited greater symptom severity than other patient groups. Across all schizophrenia subgroups, hippocampal and amygdala volumes were smaller relative to controls. Treatment-resistant patients (UTR and clozapine-responsive) also showed reduced nucleus accumbens volumes, whereas FLR patients demonstrated larger pallidal volumes. In addition, the UTR subgroup exhibited enlarged lateral ventricles. Hippocampal subfield analyses revealed widespread reductions in treatment-resistant patients, most prominently in the CA4/dentate gyrus, subiculum and stratum, whereas FLR patients showed more focal reductions in the CA4/dentate gyrus and left subiculum.

These results suggest that smaller hippocampal and amygdala volumes represent a shared neuroanatomical signature of schizophrenia, whereas reduced accumbens and enlarged pallidal volumes may differentiate treatment-resistant and treatment-responsive profiles, respectively. The findings underscore the heterogeneity of schizophrenia and highlight the need for longitudinal research to disentangle illness-related pathology from medication effects.