title: Early life stress and macaque amygdala hypertrophy: preliminary evidence for a role for the serotonin transporter gene.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, State University of New York, Downstate Medical Center Brooklyn, NY, USA.
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Coplan
authors.affiliation: Department of Psychiatry and Behavioral Sciences, State University of New York, Downstate Medical Center Brooklyn, NY, USA.
authors.forename: Hassan M
authors.initials: HM
authors.lastname: Fathy
authors.affiliation: Departamento de Psiquiatria, Neuroradiology, Universidade Federal de São Paulo São Paolo, Brazil.
authors.forename: Andrea P
authors.initials: AP
authors.lastname: Jackowski
authors.affiliation: Departments of Psychiatry, Neuroscience, and Radiology, Mount Sinai School of Medicine New York, NY, USA.
authors.forename: Cheuk Y
authors.initials: CY
authors.lastname: Tang
authors.affiliation: Psychiatry, New York State Psychiatric Institute New York, NY, USA.
authors.forename: Tarique D
authors.initials: TD
authors.lastname: Perera
authors.affiliation: Mental Health Care Line, Michael E. Debakey VA Medical Center Houston, TX, USA ; Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine Houston, TX, USA.
authors.forename: Sanjay J
authors.initials: SJ
authors.lastname: Mathew
authors.affiliation: Department of Psychiatry, Mount Sinai School of Medicine New York, NY, USA.
authors.forename: Jose
authors.initials: J
authors.lastname: Martinez
authors.affiliation: Department of Psychiatry, Yale University School of Medicine New Haven, CT, USA ; Clinical Neuroscience Division, National Center for PTSD West Haven, CT, USA.
authors.forename: Chadi G
authors.initials: CG
authors.lastname: Abdallah
authors.affiliation: Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute New York, NY, USA ; Departmets of Psychiatry and Pathology and Cell Biology, College of Physicians and Surgeons of Columbia University New York, NY, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Dwork
authors.affiliation: Departments of Psychiatry, Neuroscience, and Radiology, Mount Sinai School of Medicine New York, NY, USA.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Pantol
authors.affiliation: Departments of Psychiatry, Neuroscience, and Radiology, Mount Sinai School of Medicine New York, NY, USA.
authors.forename: David
authors.initials: D
authors.lastname: Carpenter
authors.affiliation: Comprehensive NeuroScience Corporation Westchester, NY, USA.
authors.forename: Jack M
authors.initials: JM
authors.lastname: Gorman
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Miami Health Sytems Miami, FL, USA.
authors.forename: Charles B
authors.initials: CB
authors.lastname: Nemeroff
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine Emory, GA, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owens
authors.affiliation: Department of Psychiatry, Yale University School of Medicine New Haven, CT, USA.
authors.forename: Arie
authors.initials: A
authors.lastname: Kaffman
authors.affiliation: Clinical Neuroscience Division, National Center for PTSD West Haven, CT, USA ; Department of Psychiatry, Yale University School of Medicine New Haven, CT, USA.
authors.forename: Joan
authors.initials: J
authors.lastname: Kaufman
keywords: MRI; amygdala; early life stress; non-human primates; serotonin transporter gene; stress