Psychiatrists' adherence to guideline-recommended pharmacotherapy for schizophrenia affects subcortical structural alterations in the brains of patients with schizophrenia

Improvements in psychiatric symptoms and functional outcomes for patients with schizophrenia are influenced by the adherence of psychiatrists to evidence-based treatment guidelines. Patients with schizophrenia exhibit subcortical structural alterations in the brain, such as reduced hippocampal volume and increased putamen and pallidum volumes, compared with healthy controls. However, no studies have examined whether psychiatrists' adherence to pharmacological guidelines is associated with subcortical structures in schizophrenia patients. We hypothesized that psychiatrist adherence to guideline-recommended pharmacological treatment attenuates the subcortical structural alterations that are characteristic of schizophrenia. Three hundred twenty-two patients with schizophrenia, including 42 patients with treatment-resistant schizophrenia (TRS) and 280 patients with non-TRS, underwent 1.5 or 3T MRI scanning. For each patient, psychiatrists' adherence to pharmacological guidelines for schizophrenia was assessed using the Individual Fitness Score (IFS). Seven subcortical structures, namely, the thalamus, caudate, putamen, pallidum, hippocampus, amygdala, and accumbens, were segmented using FreeSurfer. In patients with TRS, better adherence to guideline-recommended pharmacotherapy was associated with decreased volumes in the bilateral putamen (left β=-0.47, p = 8.63 × 10^-4; right β=-0.43, p = 2.70 × 10^-3) and left pallidum (β=-0.40, p = 3.03 × 10^-3). Specifically, clozapine prescription significantly contributed to decreased volumes in the bilateral putamen (left β=-0.52, p = 1.31 × 10^-4; right β=-0.50, p = 3.30 × 10^-4) and left pallidum (β=-0.37, p = 6.53 × 10^-3) in patients with TRS. In contrast, no significant correlations between adherence and any subcortical volumes were observed in patients with non-TRS (p > 0.05). These findings suggest that prescribing clozapine, which is a guideline-recommended treatment for TRS, may attenuate the characteristic subcortical structural alterations that are observed in patients with schizophrenia.