Multiscale neurobiological correlates of human neuroticism

Neuroticism is a heritable personality trait associated with negative emotionality; however, we know little regarding the association between the microscale and macroscale neurobiological substrates of human neuroticism. Cross-scale correlation analysis may provide such information. In this study, voxel-wise neuroimaging-neuroticism correlation analyses consistently showed a positive correlation between neuroticism and functional connectivity density (FCD) in the ventral striatum in 274 young Chinese adults. Partial least squares regression analysis showed that the FCD-neuroticism correlation map was significantly spatially correlated with gene expression profiles in each of six donated human brains. Neuroticism-related genes derived from the six donors consistently showed significant enrichment in the chemical synaptic transmission, circadian entrainment, long-term potentiation, inflammatory mediator regulation of transient receptor potential channels, and amphetamine addiction pathways. The protein-protein interaction analysis revealed four hub genes involved in the above pathways, including G protein subunit gamma 10, 5-hydroxytryptamine receptor 2C, prodynorphin, and calcium/calmodulin-dependent protein kinase II alpha. By combining multiscale correlation analyses and functional annotations, this study advances our understanding of the genetic and neural substrates of human neuroticism and emphasizes the importance of striatal functional properties in human neuroticism.