Neuroanatomic Differences Associated with Stress Susceptibility and Resilience

• Published in: Biological psychiatry (1969) 2016-05, Vol.79 (10), p.840-849
• Main Authors: Anacker, Christoph, Scholz, Jan, O’Donnell, Kieran J, Allemang-Grand, Rylan, Diorio, Josie, Bagot, Rosemary C, Nestler, Eric J, Hen, René, Lerch, Jason P, Meaney, Michael J
• Format: Article
• Language: English
• Subjects: Animals; Avoidance Learning; Brain - diagnostic imaging; Chronic stress; Cingulate cortex; Depression; Diffusion Tensor Imaging; Disease Susceptibility; Dominance-Subordination; DTI; Hippocampus; Magnetic Resonance Imaging; Male; Mice, Inbred C57BL; MRI; Neural circuits; Neural Pathways - diagnostic imaging; Organ Size; Psychiatry; Resilience, Psychological; Stress, Psychological - diagnostic imaging; Ventral tegmental area
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2015.08.009

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.