Mapping Individual Brain Deviations in ICD-11 Catatonia: Normative Modeling of Structural and Functional MRI Across Two Independent Cohorts

OBJECTIVE: Catatonia is a transdiagnostic psychomotor syndrome cutting across mood disorders (MODs) and schizophrenia spectrum disorders (SSDs). However, its neurobiological profiles remain poorly characterized. The authors examined structural and resting-state functional normative deviations associated with catatonia across two independent clinical cohorts, using hierarchical Bayesian normative modeling. METHODS: catatonia). Individual deviations from normative models were estimated using the PCNToolkit, based on healthy reference datasets (N=57,000 structural; N=22,000 functional). RESULTS: Catatonia diagnosis was associated with significant ventricular enlargement (third ventricle and left and right lateral ventricles; q<0.05) and cortical thinning in the left dorsal posterior cingulate and insular cortices (q<0.05) across both cohorts. Exploratory analyses identified a significant left orbitofrontal cortex (OFC) difference between MOD and SSD patients with catatonia. In the overall catatonia versus non-catatonia comparison, the OFC association survived false discovery rate correction only in models adjusted for demographic variables. Resting-state functional analyses showed reduced connectivity between sensorimotor, salience, limbic, and executive control networks at the nominal significance level, but did not survive correction for multiple comparisons. CONCLUSIONS: In the combined sample, catatonia was characterized by ventricular enlargement and cingulo-insular cortical thinning, supporting a transdiagnostic model implicating distributed motor-salience integration circuits. These findings provide reproducible, individual-level evidence for distributed brain network involvement in catatonia and identify candidate regions for future mechanistic and neuromodulation studies.