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.Significance StatementAlterations in hippocampal function linked to threat-related arousal are reliably associated with post-traumatic stress disorder (PTSD); however, how these alterations relate to the sequelae of trauma-related symptoms is unknown. Prior models based on non-trauma samples suggest that arousal may impact hippocampal neurophysiology leading to maladaptive behavior. Here we show that decreased hippocampal threat sensitivity interacts with fear-potentiated startle to predict PTSD symptoms. Specifically, individuals with high fear-potentiated startle and low, transient hippocampal threat sensitivity showed the greatest PTSD symptomology. These findings bridge literatures of threat-related arousal and hippocampal function to better understand PTSD risk.
Tanriverdi B, Gregory DF, Olino TM, Ely TD, Harnett NG, van Rooij SJH, Lebois LAM, Seligowski AV, Jovanovic T, Ressler KJ, House SL, Beaudoin FL, An X, Neylan TC, Clifford GD, Linnstaedt SD, Germine LT, Bollen KA, Rauch SL, Haran JP, Storrow AB, Lewandowski C, Musey PI Jr, Hendry PL, Sheikh S, Jones CW, Punches BE, Kurz MC, McGrath ME, Hudak LA, Pascual JL, Seamon MJ, Datner EM, Pearson C, Domeier RM, Rathlev NK, O'Neil BJ, Sanchez LD, Bruce SE, Miller MW, Pietrzak RH, Joormann J, Barch DM, Pizzagalli DA, Sheridan JF, Smoller JW, Harte SE, Elliott JM, McLean SA, Kessler RC, Koenen KC, Stevens JS, Murty VP. Hippocampal Threat Reactivity Interacts with Physiological Arousal to Predict PTSD Symptoms. J Neurosci. 2022 Jul 25:JN-RM-0911-21. doi: 10.1523/JNEUROSCI.0911-21.2022. Epub ahead of print.