A Systems Biology Model Linking Peripheral NIMETOX Biomarkers to Multilevel Brain Structural and Functional Alterations Across Major Depression and Schizophrenia
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Peripheral lipid and antioxidant-related biomarkers may help contextualize brain abnormalities across psychiatric disorders, but their relationships with brain structure, intrinsic activity, and dimensional symptoms remain incompletely characterized. In this cross-sectional study, 93 adults were recruited: 38 with major depressive disorder, 29 with schizophrenia, and 26 healthy controls. Eighty-seven participants met resting-state functional MRI quality-control criteria. Assessments included structural and functional MRI, serum lipids, albumin, apolipoprotein A-I, childhood maltreatment, psychological resilience, and clinical symptoms. Exploratory analyses combined regional imaging measures, within-network connectivity, statistical mediation, and partial least squares structural equation modeling. Group-related functional abnormalities involved parietal, sensorimotor, cingulate, insular, and temporal regions. Peripheral lipid and antioxidant-related measures were associated with regional gray matter measures and intrinsic activity. Childhood maltreatment and resilience were associated with mood-related symptom burden, whereas lower connectivity and nodal strength within the selected 11-region network were associated with psychosis-related and overall illness severity. Exploratory structural equation models accounted for 66.4% of the variance in the mood-related composite and 25.3% of the variance in local intrinsic activity. These findings describe cross-sectional relationships among peripheral biological measures, regional brain characteristics, developmental adversity, and psychopathology. They provide a framework for further investigation rather than evidence of a causal blood-to-brain sequence. Independent replication with prospectively defined measures and longitudinal assessments is needed.
