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Structural connectivity of striatal subregions in first-episode schizophrenia: links to positive symptoms and treatment response
Published online by Cambridge University Press: 24 October 2025
Abstract
Background
Schizophrenia is a severe psychiatric disorder characterised by positive symptoms, such as hallucinations and delusions, which are linked to dysregulated striatal connectivity. Although traditional models highlight the limbic striatum’s role in salience processing, emerging evidence suggests that the associative striatum, critical for cognitive control and habit formation, also plays a significant role. However, the structural connectivity underlying striatal subregions and its relationship to symptom severity and treatment response remains poorly understood.
Aims
This study aimed to investigate the structural connectivity of striatal subregions in first-episode schizophrenia (FE-SCZ) patients and to evaluate its association with positive symptoms and changes following antipsychotic treatment.
Method
We recruited 80 FE-SCZ patients and 80 healthy controls who underwent diffusion tensor imaging probabilistic tractography to assess white matter tract strength between the striatum and ten cortical targets. Longitudinal analysis was conducted in patients at baseline (within 2 weeks of initial antipsychotic exposure) and after ongoing treatment to evaluate changes in connectivity and their relationship to symptom improvement.
Results
FE-SCZ patients exhibited reduced connectivity between the dorsolateral prefrontal cortex (dlPFC) and associative striatum and increased connectivity between the anterior cingulate cortex (ACC) and associative striatum compared to controls. Longitudinal analysis revealed that antipsychotic treatment increased dlPFC–associative striatum connectivity and decreased ACC–associative striatum connectivity, which correlated with reductions in positive symptom severity.
Conclusions
These findings highlight the critical role of striatal subregions in the pathophysiology of schizophrenia, emphasising the associative striatum’s involvement in cognitive control and salience attribution. Changes in striatal connectivity after continued antipsychotic therapy may serve as a biomarker for symptom improvement, advancing our understanding of schizophrenia and guiding future therapeutic strategies.
Information
- Type
- Original Article
- Information
- Copyright
- © The Author(s), 2025. Published by Cambridge University Press on behalf of Royal College of Psychiatrists
Footnotes
*
These authors contributed equally.
**
Joint first authors.
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Liu et al. supplementary material
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