title: 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.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA Division of Developmental and Cognitive Neuroscience, Yerkes National Primate Research Center.
authors.forename: Brittany R
authors.initials: BR
authors.lastname: Howell
authors.affiliation: Division of Developmental and Cognitive Neuroscience, Yerkes National Primate Research Center.
authors.forename: Jodi
authors.initials: J
authors.lastname: Godfrey
authors.affiliation: Department of Biomedical Informatics.
authors.forename: David A
authors.initials: DA
authors.lastname: Gutman
authors.affiliation: Division of Developmental and Cognitive Neuroscience, Yerkes National Primate Research Center.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Michopoulos
authors.affiliation: Division of Neuropharmacology and Neurologic Diseases and Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA and.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Govind
authors.initials: G
authors.lastname: Nair
authors.affiliation: Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Hu
authors.affiliation: Division of Developmental and Cognitive Neuroscience, Yerkes National Primate Research Center.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Wilson
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA Division of Developmental and Cognitive Neuroscience, Yerkes National Primate Research Center.
authors.forename: Mar M
authors.initials: MM
authors.lastname: Sanchez
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016880:Anisotropy; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping; D056324:Diffusion Tensor Imaging; D004644:Emotions / Q000502:physiology; D005260:Female; D005838:Genotype; D006854:Hydrocortisone / Q000097:blood; D007091:Image Processing, Computer-Assisted; D008253:Macaca mulatta; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D025341:Principal Component Analysis; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012919:Social Behavior; D012930:Social Dominance; D013315:Stress, Psychological / Q000097:blood / Q000235:genetics* / Q000473:pathology*; D066127:White Matter / Q000473:pathology*
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins; D006854:Hydrocortisone
keywords: diffusion tensor imaging; emotional behavior; nonhuman primates; prepuberty; social stress
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