Hypothalamic subunit volumes in schizophrenia with comorbidity of metabolic syndrome

Schizophrenia and metabolic syndrome (MS) are common conditions that frequently co-occur, yet the neurobiological mechanisms underlying their comorbidity remain unclear. This study aimed to investigate whether hypothalamic structural alterations contribute to this comorbidity. A total of 194 participants were included and categorized into four groups based on diagnoses of schizophrenia and MS: schizophrenia patients with/without metabolic syndrome (SZ-wMS and SZ-nMS), and healthy controls with/without metabolic syndrome. T1-weighted structural magnetic resonance imaging (MRI) was acquired. Clinical assessments included metabolic indicators, cognitive function tests, and the Positive and Negative Syndrome Scale. Based on structural MRI, the hypothalamus was segmented into five subunits in each hemisphere. We examined the interaction effects of schizophrenia and MS on the volumes of hypothalamic subunits and conducted partial correlation and moderation analyses to explore clinical relevance. An interaction effect was found in the volume of the right superior tubular subunit (supTub), with SZ-wMS showing the greatest volume reduction. Reduced right supTub volume was associated with elevated fasting blood glucose level and higher negative symptom scores. The association between right supTub volume and negative symptom scores was moderated by triglycerides level. In the SZ-wMS group, reduced right supTub volume was associated with cognitive function scores. These findings suggest that reduced volume of the right supTub may represent a potential mechanism contributing to the comorbidity of schizophrenia and MS. The observed associations with cognitive dysfunction highlight the right supTub as a possible translational target for clinical interventions aimed at improving cognitive deficits in schizophrenia patients with comorbidity of MS.