Social subordination stress and serotonin transporter polymorphisms: Associations with brain white matter tract integrity and behavior in juvenile female macaques

Brittany R. Howell, Jodi Godfrey, David A. Gutman, Vasiliki Michopoulos, Xiaodong Zhang, Govind Nair, Xiaoping Hu, Mark E. Wilson, Mar M. Sanchez

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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 genotyperelated 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.

Original languageEnglish (US)
Pages (from-to)3334-3349
Number of pages16
JournalCerebral Cortex
Volume24
Issue number12
DOIs
StatePublished - Dec 1 2014

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health (National Institute of Mental Health: grant numbers MH079100, P50 MH078105, and MH078105-S1, MH091645, and F31 MH086203 to B.R.H., F31 MH085445 to V.M.; National Institute of Child Health & Human Development: HD055255) and the National Center for Research Resources (grant number P51RR165—YNPRC base grant—currently supported by the Office of Research Infrastructure Programs/OD—grant number OD P51OD11132). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health or National Institute of Child Health & Human Development or the National Institutes of Health.

Keywords

  • Diffusion tensor imaging
  • Emotional behavior
  • Nonhuman primates
  • Prepuberty
  • Social stress

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