ArticleFrontiers in systems neuroscience2025
Network-based mapping and neurotransmitter architecture of gray matter correlates of neuroticism.
Article in Frontiers in systems neuroscience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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7 authors.
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Abstract
Objectives: Although neuroticism is a major risk factor for adverse health outcomes, its neural basis is obscured by inconsistent findings from studies of regional gray matter volume (GMV) correlates. This study sought to identify convergent functional brain networks underlying these heterogeneous GMV correlates using functional connectivity network mapping (FCNM), and to explore their neurochemical basis. Methods: We systematically identified 10 voxel-based morphometry (VBM) studies ( Results: Despite spatial heterogeneity, neuroticism-related GMV changes consistently mapped onto three principal functional networks: the default mode network (DMN), frontoparietal network (FPN), and ventral attention network (VAN). These mappings were robust across varied analytical parameters. Moreover, the implicated networks demonstrated significant spatial correlation with the distributions of 5-hydroxytryptamine receptor 2A (5-HT2A), cannabinoid receptor type 1 (CB1), and metabotropic glutamate receptor 5 (mGluR5). Conclusion: 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.
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