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Neuroanatomic Differences Associated With Stress Susceptibility and Resilience

  • Christoph Anacker
    Affiliations
    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
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  • Jan Scholz
    Affiliations
    Mouse Imaging Centre, Hospital for Sick Children, and Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
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  • Kieran J. O’Donnell
    Affiliations
    Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada
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  • Rylan Allemang-Grand
    Affiliations
    Mouse Imaging Centre, Hospital for Sick Children, and Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
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  • Josie Diorio
    Affiliations
    Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada
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  • Rosemary C. Bagot
    Affiliations
    Fishberg Department of Neuroscience Icahn School of Medicine at Mount Sinai, Singapore

    Friedman Brain Institute, Icahn School of Medicine at Mount Sinai; Singapore
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  • Eric J. Nestler
    Affiliations
    Fishberg Department of Neuroscience Icahn School of Medicine at Mount Sinai, Singapore

    Friedman Brain Institute, Icahn School of Medicine at Mount Sinai; Singapore
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  • René Hen
    Affiliations
    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
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  • Jason P. Lerch
    Affiliations
    Mouse Imaging Centre, Hospital for Sick Children, and Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
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  • Michael J. Meaney
    Correspondence
    Address correspondence to Michael J. Meaney, Ph.D., Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, 6875 LaSalle, Montreal, Quebec H4H 1R3, Canada
    Affiliations
    Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada

    Singapore Institute for Clinical Sciences, Singapore
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      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.

      Keywords

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