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Distinct subcortical neuroanatomic profiles of treatment-resistant schizophrenia: structural magnetic resonance
Ibrahim Sungur1,2, Simay Selek1, Kaan Keskin1,2
1SoCAT Lab, Department of Psychiatry, School of Medicine, https://ror.org/05xv0p989Ege University, Izmir, Turkey.
Background:
Understanding the neuroanatomical correlates of treatment response in schizophrenia is crucial for improving clinical stratification and clarifying underlying pathophysiological mechanisms.
Aims:
To examine subcortical volumetric differences across clinically defined schizophrenia treatment-response subgroups.
Method:
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.
Results:
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.
Conclusions:
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.
