Hippocampal Threat Reactivity Interacts with Physiological Arousal to Predict PTSD Symptoms.

Hippocampal impairments are reliably associated with post-traumatic stress disorder (PTSD); however, little research has characterized how increased threat-sensitivity may interact with arousal responses to alter hippocampal reactivity, and further how these interactions relate to the sequelae of trauma-related symptoms. In a sample of individuals recently exposed to trauma (N=116, 76 Female), we found that PTSD symptoms at 2-weeks were associated with decreased hippocampal responses to threat as assessed with functional magnetic resonance imaging (fMRI). Further, the relationship between hippocampal threat sensitivity and PTSD symptomology only emerged in individuals who showed transient, high threat-related arousal, as assayed by an independently collected measure of Fear Potentiated Startle. Collectively, our finding suggests that development of PTSD is associated with threat-related decreases in hippocampal function, due to increases in fear-potentiated arousal.

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Dr. Ressler has served on advisory boards for Takeda, Resilience Therapeutics, Janssen and Verily/Google. His research has been sponsored by Alkermes and Brainsway and he has worked as a consultant for Alkermes. In the last three years, Dr. Clifford has received research funding from the NSF, NIH and LifeBell AI, and unrestricted donations from AliveCor, Amazon Research, the Center for Discovery, the Gordon and Betty Moore Foundation, MathWorks, Microsoft Research, the Gates Foundation, Google, One Mind Foundation, and Samsung Research. Dr. Clifford has financial interest in AliveCor and receives unrestricted funding from the company. He also is the CTO of MindChild Medical and CSO of LifeBell AI and has ownership in both companies. These relationships are unconnected to the current work. Dr. Germine is on the scientific advisory board of the nonprofit Sage Bionetworks, for which she receives a small honorarium. Dr. Sheikh has received funding from the Florida Medical Malpractice Joint Underwriter’s Association Dr. Alvin E. Smith Safety of Healthcare Services Grant, Allergan Foundation, the NIH/NIA-funded Jacksonville Aging Studies Center (JAX-ASCENT; R33AG05654), the Substance Abuse and Mental Health Services Administration (1H79TI083101-01), and the Florida Blue Foundation. Dr. Jones reports no direct conflicts related to this paper, and no ongoing conflicts. He has been an investigator on studies funded by Hologic Inc, Janssen, and AstraZeneca, for which his department has received research funding. Over the past 3 years, Dr. Pizzagalli has received consulting fees from BlackThorn Therapeutics, Boehringer Ingelheim, Compass Pathway, Concert Pharmaceuticals, Engrail Therapeutics, Neurocrine Biosciences, Otsuka Pharmaceuticals, and Takeda Pharmaceuticals; one honorarium from Alkermes, and research funding from Millennium Pharmaceuticals. In addition, he has received stock options from BlackThorn Therapeutics. No funding from these entities was used to support the current work, and all views expressed are solely those of the authors. Dr. Elliott reports support from the National Institutes of Health (NIH) through Grant Numbers R01HD079076 & R03HD094577, Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Center for Medical Rehabilitation Research, and South Wales Health Spinal Cord Injury Research Grants Program. In the past 3 years, Dr. Kessler was a consultant for Datastat, Inc., RallyPoint Networks, Inc., Sage Pharmaceuticals, and Takeda. The remaining authors report no financial relationships with commercial interests.