Jennifer S Stevens1, Ye Ji Kim2, Isaac R Galatzer-Levy3, Renuka Reddy2, Timothy D Ely2, Charles B Nemeroff4, Lauren A Hudak5, Tanja Jovanovic2, Barbara O Rothbaum2, Kerry J Ressler6. 1. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia. Electronic address: jennifer.stevens@emory.edu. 2. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia. 3. Department of Psychiatry, New York University School of Medicine, New York, New York. 4. Department of Psychiatry and Behavioral Sciences, University of Miami Leonard M. Miller School of Medicine, Miami, Florida. 5. Department of Emergency Medicine, Emory University School of Medicine, Atlanta, Georgia. 6. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia; Department of Psychiatry, Harvard Medical School, Cambridge, Massachusetts; McLean Hospital, Belmont, Massachusetts.
Abstract
BACKGROUND: Studies suggest that exaggerated amygdala reactivity is a vulnerability factor for posttraumatic stress disorder (PTSD); however, our understanding is limited by a paucity of prospective, longitudinal studies. Recent studies in healthy samples indicate that, relative to reactivity, habituation is a more reliable biomarker of individual differences in amygdala function. We investigated reactivity of the amygdala and cortical areas to repeated threat presentations in a prospective study of PTSD. METHODS: Participants were recruited from the emergency department of a large level I trauma center within 24 hours of trauma. PTSD symptoms were assessed at baseline and approximately 1, 3, 6, and 12 months after trauma. Growth curve modeling was used to estimate symptom recovery trajectories. Thirty-one individuals participated in functional magnetic resonance imaging around the 1-month assessment, passively viewing fearful and neutral face stimuli. Reactivity (fearful > neutral) and habituation to fearful faces was examined. RESULTS: Amygdala reactivity, but not habituation, 5 to 12 weeks after trauma was positively associated with the PTSD symptom intercept and predicted symptoms at 12 months after trauma. Habituation in the ventral anterior cingulate cortex was positively associated with the slope of PTSD symptoms, such that decreases in ventral anterior cingulate cortex activation over repeated presentations of fearful stimuli predicted increasing symptoms. CONCLUSIONS: Findings point to neural signatures of risk for maintaining PTSD symptoms after trauma exposure. Specifically, chronic symptoms were predicted by amygdala hyperreactivity, and poor recovery was predicted by a failure to maintain ventral anterior cingulate cortex activation in response to fearful stimuli. The importance of identifying patients at risk after trauma exposure is discussed.
BACKGROUND: Studies suggest that exaggerated amygdala reactivity is a vulnerability factor for posttraumatic stress disorder (PTSD); however, our understanding is limited by a paucity of prospective, longitudinal studies. Recent studies in healthy samples indicate that, relative to reactivity, habituation is a more reliable biomarker of individual differences in amygdala function. We investigated reactivity of the amygdala and cortical areas to repeated threat presentations in a prospective study of PTSD. METHODS:Participants were recruited from the emergency department of a large level I trauma center within 24 hours of trauma. PTSD symptoms were assessed at baseline and approximately 1, 3, 6, and 12 months after trauma. Growth curve modeling was used to estimate symptom recovery trajectories. Thirty-one individuals participated in functional magnetic resonance imaging around the 1-month assessment, passively viewing fearful and neutral face stimuli. Reactivity (fearful > neutral) and habituation to fearful faces was examined. RESULTS: Amygdala reactivity, but not habituation, 5 to 12 weeks after trauma was positively associated with the PTSD symptom intercept and predicted symptoms at 12 months after trauma. Habituation in the ventral anterior cingulate cortex was positively associated with the slope of PTSD symptoms, such that decreases in ventral anterior cingulate cortex activation over repeated presentations of fearful stimuli predicted increasing symptoms. CONCLUSIONS: Findings point to neural signatures of risk for maintaining PTSD symptoms after trauma exposure. Specifically, chronic symptoms were predicted by amygdala hyperreactivity, and poor recovery was predicted by a failure to maintain ventral anterior cingulate cortex activation in response to fearful stimuli. The importance of identifying patients at risk after trauma exposure is discussed.
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