TY - JOUR
T1 - Neuroanatomic Differences Associated with Stress Susceptibility and Resilience
AU - Anacker, Christoph
AU - Scholz, Jan
AU - O'Donnell, Kieran J.
AU - Allemang-Grand, Rylan
AU - Diorio, Josie
AU - Bagot, Rosemary C.
AU - Nestler, Eric J.
AU - Hen, René
AU - Lerch, Jason P.
AU - Meaney, Michael J.
N1 - Publisher Copyright:
© 2016 Published by Elsevier Inc on behalf of Society of Biological Psychiatry
PY - 2016/5/15
Y1 - 2016/5/15
N2 - 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.
AB - 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.
KW - Chronic stress
KW - Cingulate cortex
KW - DTI
KW - Depression
KW - Hippocampus
KW - MRI
KW - Neural circuits
KW - Ventral tegmental area
UR - http://www.scopus.com/inward/record.url?scp=84945353518&partnerID=8YFLogxK
U2 - 10.1016/j.biopsych.2015.08.009
DO - 10.1016/j.biopsych.2015.08.009
M3 - Article
C2 - 26422005
AN - SCOPUS:84945353518
SN - 0006-3223
VL - 79
SP - 840
EP - 849
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 10
ER -