title: Neuroanatomic Differences Associated With Stress Susceptibility and Resilience.
abstract: BACKGROUND
  We examined the neurobiological mechanisms underlying stress susceptibility using structural magnetic resonance imaging and diffusion tensor imaging to determine neuroanatomic differences between stress-susceptible and resilient mice. We also examined synchronized anatomic differences between brain regions to gain insight into the plasticity of neural networks underlying stress susceptibility.
  
  
  METHODS
  C57BL/6 mice underwent 10 days of social defeat stress and were subsequently tested for social avoidance. For magnetic resonance imaging, brains of stressed (susceptible, n = 11; resilient, n = 8) and control (n = 12) mice were imaged ex vivo at 56 µm resolution using a T2-weighted sequence. We tested for behavior-structure correlations by regressing social avoidance z-scores against local brain volume. For diffusion tensor imaging, brains were scanned with a diffusion-weighted fast spin echo sequence at 78 μm isotropic voxels. Structural covariance was assessed by correlating local volume between brain regions.
  
  
  RESULTS
  Social avoidance correlated negatively with local volume of the cingulate cortex, nucleus accumbens, thalamus, raphe nuclei, and bed nucleus of the stria terminals. Social avoidance correlated positively with volume of the ventral tegmental area (VTA), habenula, periaqueductal gray, cerebellum, hypothalamus, and hippocampal CA3. Fractional anisotropy was increased in the hypothalamus and hippocampal CA3. We observed synchronized anatomic differences between the VTA and cingulate cortex, hippocampus and VTA, hippocampus and cingulate cortex, and hippocampus and hypothalamus. These correlations revealed different structural covariance between brain regions in susceptible and resilient mice.
  
  
  CONCLUSIONS
  Stress-integrative brain regions shape the neural architecture underlying individual differences in susceptibility and resilience to chronic stress.
authors.affiliation: Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada; Department of Psychiatry, New York State Psychiatric Institute/Research Foundation for Mental Hygiene, Inc., New York, New York; Columbia University, and Division of Integrative Neuroscience, New York State Psychiatric Institute/Research Foundation for Mental Hygiene, Inc., New York, New York.
authors.forename: Christoph
authors.initials: C
authors.lastname: Anacker
authors.affiliation: Mouse Imaging Centre, Hospital for Sick Children, and Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jan
authors.initials: J
authors.lastname: Scholz
authors.affiliation: Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Kieran J
authors.initials: KJ
authors.lastname: O'Donnell
authors.affiliation: Mouse Imaging Centre, Hospital for Sick Children, and Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Rylan
authors.initials: R
authors.lastname: Allemang-Grand
authors.affiliation: Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Josie
authors.initials: J
authors.lastname: Diorio
authors.affiliation: Fishberg Department of Neuroscience Icahn School of Medicine at Mount Sinai, Singapore; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai; Singapore.
authors.forename: Rosemary C
authors.initials: RC
authors.lastname: Bagot
authors.affiliation: Fishberg Department of Neuroscience Icahn School of Medicine at Mount Sinai, Singapore; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai; Singapore.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Nestler
authors.affiliation: Department of Psychiatry, New York State Psychiatric Institute/Research Foundation for Mental Hygiene, Inc., New York, New York; Department of Neuroscience, New York State Psychiatric Institute/Research Foundation for Mental Hygiene, Inc., New York, New York; Department ofPharmacology, New York State Psychiatric Institute/Research Foundation for Mental Hygiene, Inc., New York, New York; Columbia University, and Division of Integrative Neuroscience, New York State Psychiatric Institute/Research Foundation for Mental Hygiene, Inc., New York, New York.
authors.forename: René
authors.initials: R
authors.lastname: Hen
authors.affiliation: Mouse Imaging Centre, Hospital for Sick Children, and Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Lerch
authors.affiliation: Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada; Singapore Institute for Clinical Sciences, Singapore. Electronic address: michael.meaney@mcgill.ca.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Meaney
mesh_terms: D000818:Animals; D001362:Avoidance Learning; D001921:Brain / Q000000981:diagnostic imaging*; D056324:Diffusion Tensor Imaging; D004198:Disease Susceptibility; D004291:Dominance-Subordination; D008279:Magnetic Resonance Imaging; D008297:Male; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000000981:diagnostic imaging; D009929:Organ Size; D055500:Resilience, Psychological; D013315:Stress, Psychological / Q000000981:diagnostic imaging*
keywords: Chronic stress; Cingulate cortex; DTI; Depression; Hippocampus; MRI; Neural circuits; Ventral tegmental area