Hippocampal Threat Reactivity Interacts with Physiological Arousal to Predict PTSD Symptoms

• DOI: 10.1523/jneurosci.0911-21.2022
• Publication Date: 2022-07-25T17:50:13Z
• Authors: Büşra Tanriverdi; David F. Gregory; Thomas M. Olino; Timothy D. Ely; Nathaniel G. Harnett; Sanne J.H. van Rooij; Lauren A.M. Lebois; Antonia V. Seligo...; Tanja Jovanovic; Kerry J. Ressler; Stacey L. House; Francesca L. Beau...; Xinming An; Thomas C. Neylan; Gari D. Clifford; Sarah D. Linnstaedt; Laura T. Germine; Kenneth A. Bollen; Scott L. Rauch; John P. Haran; Alan B. Storrow; Christopher Lewan...; Paul I. Musey; Phyllis L. Hendry; Sophia Sheikh; Christopher W. Jones; Brittany E. Punches; Michael C. Kurz; Meghan E. McGrath; Lauren A. Hudak; Jose L. Pascual; Mark J. Seamon; Elizabeth M. Datner; Claire Pearson; Robert M. Domeier; Niels K. Rathlev; Brian J. O'Neil; Leon D. Sanchez; Steven E. Bruce; Mark W. Miller; Robert H. Pietrzak; Jutta Joormann; Deanna M. Barch; Diego A. Pizzagalli; John F. Sheridan; Jordan W. Smoller; Steven E. Harte; James M. Elliott; Samuel A. McLean; Ronald C. Kessler; Karestan C. Koenen; Jennifer S. Stevens; Vishnu P. Murty
• Keywords: hippocampus; fMRI; 150; Fear; Hippocampus; Trauma; 3. Good health; 03 medical and health sciences; trauma; 0302 clinical medicine; arousal; Emergency Medicine; Medicine and Health Sciences; fear; Arousal

Prior studies highlight how threat-related arousal may impair hippocampal function. Hippocampal impairments are reliably associated with post-traumatic stress disorder (PTSD); however, little research has characterized how increased threat-sensitivity may drive arousal responses to alter hippocampal reactivity, and further how these alterations relate to the sequelae of trauma-related symptoms. In a sample of individuals recently exposed to trauma (N=117, 76 Female), we found that PTSD symptoms at 2-weeks and 3-months were associated with decreased hippocampal responses to threat as assessed with functional magnetic resonance imaging (fMRI). Further, decreased hippocampal threat sensitivity was predicted by individual differences in fear-potentiated startle, an arousal-mediated behavior. Critically, the relationship between hippocampal threat sensitivity and PTSD symptomology only emerged in individuals who showed high threat-related arousal. Collectively, our finding suggests that development of PTSD is associated with threat-related decreases in hippocampal function, due to increases in fear-potentiated arousal.