Different Clozapine Response in Treatment-resistant Schizophrenia in the Context of Structural MRI and Resting State EEG

Background: the identification of distinct schizophrenia subtypes based on therapeutic response, as well as the search for biomarkers of clozapine response, is still in its early stages.

Objective: to establish the profile of structural and functional abnormalities of the brain in groups of ultra-treatment-resistant schizophrenia patients (UTRS) and clozapine responders (CRS), as well as the associations of the identied abnormalities with clinical characteristics.

Patients and Methods: two groups of right-handed male patients diagnosed with paranoid schizophrenia (F20.0) and healthy controls underwent MRI, EEG and clinical examination. The MRI data analysis included 15 patients of the CRS group, 18 patients of the UTRS group, and 21 healthy controls. In the EEG data analysis, the samples consisted of 12 and 15 patients, respectively, while the control group was selected separately and included 26 subjects. For the analysis of MRI data, T1-weighted images were processed using FreeSurfer 7.1.1. For each subject, values for the cortical, subcortical, and brain stem structures were obtained. For EEG analysis, spectral power (SP) values of theta, alpha and gamma rhythms were obtained. Intergroup comparisons and correlations with clinical scales (PANSS, CDSS) and antipsychotic dosage in chlorpromazine equivalent were performed.

Results: in the UTRS group, changes in subcortical structures similar to those in the CR group were observed, along with a decrease in the cortical thickness (in CRS compared to control — right temporal cortex; in UTRS — frontal, temporal, occipital, insular, and cingulate cortices bilaterally). Additionally, the theta rhythm SP was higher in both groups. The theta rhythm SP correlated with the average daily dose of antipsychotics in the UTRS group.

Conclusion: the results indicate that ultra-treatment-resistance is associated with more widespread and pronounced cortical thinning. The effects of the therapy were primarily noted in functional characteristics (theta rhythm SP), although indirect effects from changes in the state of the brain cannot be excluded.

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