Post-traumatic stress disorder (PTSD) is a chronic disease caused by traumatic incidents. Numerous studies have revealed grey matter volume differences in affected individuals. The nature of the disease renders it difficult to distinguish between a priori versus a posteriori changes. To overcome this difficulty, we studied the consequences of a traumatic event on brain morphology in mice before and 4 weeks after exposure to brief foot shocks (or sham treatment), and correlated morphology with symptoms of hyperarousal. In the latter context, we assessed hyperarousal upon confrontation with acoustic, visual, or composite (acoustic/visual/tactile) threats and integrated the individual readouts into a single Hyperarousal Score using logistic regression analysis. MRI scans with subsequent whole-brain deformation-based morphometry (DBM) analysis revealed a volume decrease of the dorsal hippocampus and an increase of the reticular nucleus in shocked mice when compared to non-shocked controls. Using the Hyperarousal Score as regressor for the post-exposure MRI measurement, we observed negative correlations with several brain structures including the dorsal hippocampus. If the development of changes with respect to the basal MRI was considered, reduction in globus pallidus volume reflected hyperarousal severity. Our findings demonstrate that a brief traumatic incident can cause volume changes in defined brain structures and suggest the globus pallidus as an important hub for the control of fear responses to threatening stimuli of different sensory modalities.

Department Stress Neurobiology and Neurogenetics Max Planck Institute of Psychiatry 80804 Munich Germany; Department of Neurobiology Weizmann Institute of Science 76100 Rehovot Israel

Department Stress Neurobiology and Neurogenetics Max Planck Institute of Psychiatry 80804 Munich Germany; International Max Planck Research School for Translational Psychiatry 80804 Munich Germany

International Max Planck Research School for Translational Psychiatry 80804 Munich Germany; Department Translational Research in Psychiatry Max Planck Institute of Psychiatry 80804 Munich Germany

Research Group Neuronal Plasticity Max Planck Institute of Psychiatry 80804 Munich Germany

Research Group Neuronal Plasticity Max Planck Institute of Psychiatry 80804 Munich Germany; Max Planck School of Cognition 04103 Leipzig Germany

Research Group Neuronal Plasticity Max Planck Institute of Psychiatry 80804 Munich Germany; Max Planck School of Cognition 04103 Leipzig Germany; Central Nervous System Diseases Research Boehringer Ingelheim Pharma GmbH and Co KG 88397 Biberach an der Riss Germany

Scientific Core Unit Neuroimaging Max Planck Institute of Psychiatry 80804 Munich Germany

Scientific Core Unit Neuroimaging Max Planck Institute of Psychiatry 80804 Munich Germany; Department of Pharmacology Faculty of Medicine Masaryk University 62500 Brno Czechia

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