Magnetic resonance texture alterations in the caudate nucleus following 18 weeks of clozapine treatment in patients with treatment-resistant schizophrenia

Clozapine is the gold-standard treatment for treatment-resistant schizophrenia (TRS), yet its mechanism of action remains unclear. Previous studies implicated the caudate nucleus as a potential key region of clozapine-related structural changes. Texture analysis (TA), a quantitative image analysis technique that may sensitively capture subtle alterations of the underlying tissue microstructure, was utilized to investigate changes in the caudate following 18 weeks of clozapine treatment. Thirty-three patients with TRS initiated on clozapine and 31 first-line antipsychotic responders (FLR) on stable doses of antipsychotics underwent T1-weighted magnetic resonance imaging scans twice, at screening and at the 18-week study endpoint. The TRS group was subdivided into clozapine-responsive schizophrenia (CRS) and ultra-TRS (UTRS) groups based on treatment response to clozapine. Three-dimensional TA was performed using the gray-level co-occurrence matrix (GLCM). Texture features were extracted from the left and right caudate. A significant group-by-time interaction for TRS and FLR was observed in the GLCM Correlation of the left caudate. Both CRS and UTRS groups exhibited significant reductions in GLCM Correlation after 18 weeks of clozapine treatment compared to the FLR group. The CRS group exhibited greater baseline GLCM Correlation than the UTRS and FLR groups. Texture changes were observed in both the CRS and UTRS, suggesting a shared neural reorganization potentially linked to clozapine treatment. This may imply transition toward a more complex/heterogeneous caudate texture. By capturing early/dynamic microstructural changes following clozapine treatment, these findings may provide new insights into the neurobiological mechanisms underlying clozapine-induced modification of the caudate nucleus in TRS.