Early life stress and macaque annygdala hypertrophy: preliminary evidence for a role for the serotonin transporter gene

• Authors: Jeremy D. Coplan, Emory University; Hassan M. Fathy, Emory University; Andrea P. Jackowski, Universidade Federal de São Paulo; Cheuk Y. Tang, Mount Sinai School of Medicine; Tarique D. Perera, New York State Psychiatric Institute; Sanjay J. Mathew, Michael E. Debakey VA Medical Center; Jose Martinez, Mount Sinai School of Medicine; Chadi G. Abdallah, Yale University School of Medicine; Andrew J. Dwork, New York State Psychiatric Institute; Gustavo Pantol, Mount Sinai School of Medicine; David Carpenter, Mount Sinai School of Medicine; Jack M. Gorman, Comprehensive NeuroScience Corporation; Charles B. Nemeroff, University of Miami Health Sytems; Michael Owens, Emory University; Arie Kaffman, Yale University School of Medicine; Joan Kaufman, National Center for PTSD
• Journal Title: Frontiers in Behavioral Neuroscience
• Volume: Volume 8, Number OCT
• Publisher: Frontiers | 2014-10-06, Pages 342-342
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.3389/fnbeh.2014.00342
• Subjects: Psychology, General; Psychology, Behavioral; Biology, Neuroscience
• Keywords: Science & Technology; Life Sciences & Biomedicine; Behavioral Sciences; Neurosciences; Neurosciences & Neurology; amygdala; early life stress; non-human primates; MRI; stress; serotonin transporter gene; CORTICOTROPIN-RELEASING-FACTOR; LINKED POLYMORPHIC REGION; ADULT NONHUMAN-PRIMATES; D-ASPARTATE RECEPTORS; DENTATE GYRUS; PERSONALITY-DISORDER; INTERNAL CAPSULE; BONNET MACAQUES; AMYGDALA VOLUME; ANTERIOR LIMB

Abstract

Background: Children exposed to early life stress (ELS) exhibit enlarged amygdala volume in comparison to controls. The primary goal of this study was to examine amygdala volumes in bonnet macaques subjected to maternal variable foraging demand (VFD) rearing, a well-established model of ELS. Preliminary analyses examined the interaction of ELS and the serotonin transporter gene on amygdala volume. Secondary analyses were conducted to examine the association between amygdala volume and other stress-related variables previously found to distinguish VFD and non-VFD reared animals. Methods: Twelve VFD-reared and nine normally reared monkeys completed MRI scans on a 3T system (mean age = 5.2 years). Results: Left amygdala volume was larger in VFD vs. control macaques. Larger amygdala volume was associated with: “high” cerebrospinal fluid concentrations of corticotropin releasing-factor (CRF) determined when the animals were in adolescence (mean age = 2.7 years); reduced fractional anisotropy (FA) of the anterior limb of the internal capsule (ALIC) during young adulthood (mean age = 5.2 years) and timid anxiety-like responses to an intruder during full adulthood (mean age = 8.4 years). Right amygdala volume varied inversely with left hippocampal neurogenesis assessed in late adulthood (mean age = 8.7 years). Exploratory analyses also showed a gene-by-environment effect, with VFD-reared macaques with a single short allele of the serotonin transporter gene exhibiting larger amygdala volume compared to VFD-reared subjects with only the long allele and normally reared controls. Conclusion: These data suggest that the left amygdala exhibits hypertrophy after ELS, particularly in association with the serotonin transporter gene, and that amygdala volume variation occurs in concert with other key stress-related behavioral and neurobiological parameters observed across the lifecycle. Future research is required to understand the mechanisms underlying these diverse and persistent changes associated with ELS and amygdala volume.