Social Subordination Stress and Serotonin Transporter Polymorphisms: Associations With Brain White Matter Tract Integrity and Behavior in Juvenile Female Macaques

Abstract

We examined the relationship between social rank and brain white matter (WM) microstructure, and socioemotional behavior, and its modulation by serotonin (5HT) transporter (5HTT) polymorphisms in prepubertal female macaques. Using diffusion tensor imaging and tract-based spatial statistics, social status differences were found in medial prefrontal cortex (mPFC) WM and cortico-thalamic tracts, with subordinates showing higher WM structural integrity (measured as fractional anisotropy, FA) than dominant animals. 5HTT genotype-related differences were detected in the posterior limb of the internal capsule, where s-variants had higher FA than l/l animals. Status by 5HTT interaction effects were found in (1) external capsule (middle longitudinal fasciculus), (2) parietal WM, and (3) short-range PFC tracts, with opposite effects in dominant and subordinate animals. In most regions showing FA differences, opposite differences were detected in radial diffusivity, but none in axial diffusivity, suggesting that differences in tract integrity likely involve differences in myelin. These findings highlight that differences in social rank are associated with differences in WM structural integrity in juveniles, particularly in tracts connecting prefrontal, sensory processing, motor and association regions, sometimes modulated by 5HTT genotype. Differences in these tracts were associated with increased emotional reactivity in subordinates, particularly with higher submissive and fear behaviors.