title: Trauma exposure relates to heightened stress, altered amygdala morphology and deficient extinction learning: Implications for psychopathology.
abstract: Stress exposure causes a structural reorganization in neurons of the amygdala. In particular, animal models have repeatedly shown that both acute and chronic stress induce neuronal hypertrophy and volumetric increase in the lateral and basolateral nuclei of amygdala. These effects are visible on the behavioral level, where stress enhances anxiety behaviors and provokes greater fear learning. We assessed stress and anxiety levels in a group of 18 healthy human trauma-exposed individuals (TR group) compared to 18 non-exposed matched controls (HC group), and related these measurements to amygdala volume. Traumas included unexpected adverse experiences such as vehicle accidents or sudden loss of a loved one. As a measure of aversive learning, we implemented a cued fear conditioning paradigm. Additionally, to provide a biological marker of chronic stress, we measured the sensitivity of the hypothalamus-pituitary-adrenal (HPA) axis using a dexamethasone suppression test. Compared to the HC, the TR group showed significantly higher levels of chronic stress, current stress and trait anxiety, as well as increased volume of the left amygdala. Specifically, we observed a focal enlargement in its lateral portion, in line with previous animal data. Compared to HC, the TR group also showed enhanced late acquisition of conditioned fear and deficient extinction learning, as well as salivary cortisol hypo-suppression to dexamethasone. Left amygdala volumes positively correlated with suppressed morning salivary cortisol. Our results indicate differences in trauma-exposed individuals which resemble those previously reported in animals exposed to stress and in patients with post-traumatic stress disorder and depression. These data provide new insights into the mechanisms through which traumatic stress might prompt vulnerability for psychopathology.
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, 68159 Mannheim, Germany; Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Passeig de la vall d'Hebron 171, Barcelona, Catalonia, Spain. Electronic address: raffaele.cacciaglia@ub.edu.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Cacciaglia
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, 68159 Mannheim, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Nees
authors.affiliation: Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital of Frankfurt, Frankfurt, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Grimm
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, 68159 Mannheim, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Ridder
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, 68159 Mannheim, Germany.
authors.forename: Sebastian T
authors.initials: ST
authors.lastname: Pohlack
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, 68159 Mannheim, Germany.
authors.forename: Slawomira J
authors.initials: SJ
authors.lastname: Diener
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, 68159 Mannheim, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Liebscher
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, 68159 Mannheim, Germany. Electronic address: herta.flor@zi-mannheim.de.
authors.forename: Herta
authors.initials: H
authors.lastname: Flor
mesh_terms: D000328:Adult; D000679:Amygdala / Q000000981:diagnostic imaging / Q000473:pathology*; D003214:Conditioning, Classical / Q000502:physiology*; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D000067073:Psychological Trauma / Q000150:complications*; D012463:Saliva / Q000737:chemistry; D013313:Stress Disorders, Post-Traumatic / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D055815:Young Adult
chemical_list: D006854:Hydrocortisone
keywords: Amygdala; Depression; Extinction learning; Fear conditioning; Post-traumatic stress disorder; Stress; Trauma