Network-based mapping and neurotransmitter architecture of gray matter correlates of neuroticism

Despite regional variability, GMV correlates of neuroticism converge on common large-scale brain networks involved in self-referential processing, cognitive control, and salience processing. Their significant spatial coupling with 5-HT2A, CB1, and mGluR5 receptor distributions suggests serotonergic, endocannabinoid, and glutamatergic modulatory mechanisms contributing to network-level alterations. This cross-modal and network-based approach provides a unified framework for understanding the biological substrates of neuroticism, reconciling prior inconsistencies, and identifying key targets for prevention or biomarker development.