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Dimensional and Categorical Predictors of Theory of Mind Network Activation: A transdiagnostic fMRI Study in Psychiatric Inpatients

Nagel, P. M.; Hefner, S.; Said-Yuerekli, S.; Freinhofer, D.; Winds, K.; Freinhofer, D.; Kronbichler, M.; Kronbichler, L.

2026-09-22 neuroscience
10.64898/2026.09.21.753139 bioRxiv
Show abstract

Socio-cognitive alterations are widely observed across different psychiatric conditions, yet it remains unclear whether these deficits map onto distinct diagnostic categories or represent a shared transdiagnostic phenotype, driven by dimensional psychopathological symptom severity.This study evaluates Theory of Mind (ToM) network activation during a naturalistic functional magnetic resonance imaging (fMRI) movie paradigm in 313 participants, including 91 healthy controls and 222 psychiatric inpatients across five distinct diagnostic clusters (substance use, schizophrenia spectrum, affective, anxiety, and personality disorders). Frequentist analyses revealed decreased ToM-selective activity in psychiatric patients, compared to controls across all ToM regions of interest (ROIs). No significant difference emerged between diagnostic groups, but ROI activation correlated negatively with Adult Self-Report (ASR) scales (Total Problems, Internalising, Externalising). Subsequent Bayesian analysis of covariance (ANCOVAs) consistently favoured models that excluded traditional categorical diagnoses, suggesting that dimensional measures, especially Total Problems and Internalising, provided substantially greater predictive utility for ToM-related regional brain activation. Our findings challenge traditional categorical classifications in neurobiological research as they suggest that atypical mentalising might reflect a shared transdiagnostic vulnerability.

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