Amygdala Hyperactivity in Posttraumatic Stress Disorder: Disentangling Predisposing From Consequential Factors Using a Prospective Longitudinal Design

Biological Psychiatry, vol. 98, pp. 427–435

Abstract

BACKGROUND: Substantial interindividual differences exist in the vulnerability to develop posttraumatic stress disorder (PTSD) symptoms following trauma exposure. Identification of neurocognitive risk markers for PTSD symptoms could aid early assessment and identification of preventive intervention targets for PTSD, particularly in high-risk professionals. Therefore, large prospective longitudinal studies with pretrauma measurements are essential to disentangle whether previously observed neurobiological alterations in PTSD are a cause or consequence of trauma exposure or PTSD symptoms. METHODS: In police recruits (n = 221) without current trauma symptoms but at high risk for trauma exposure, we used functional magnetic resonance imaging to disentangle predictive and acquired neural markers of posttraumatic stress symptoms. Using an experimental paradigm, we investigated anticipatory threat responses and the switch into defensive action. RESULTS: Recruits who showed relatively heightened dorsal amygdala responses and heightened amygdala-precuneus coupling during threat anticipation demonstrated relatively stronger increase in PTSD symptoms after trauma exposure. The experience of traumatic events, independent of PTSD symptoms, was associated with increased lateral amygdala activation in response to an aversive stimulus (i.e., receiving an electrical shock). CONCLUSIONS: This prospective longitudinal study shows a predictive role for dorsal amygdala responsivity during threat anticipation for the development of trauma symptoms, while lateral amygdala responding to aversive events after trauma may reflect a failure to regulate. Our findings not only inform neurobiological theories of PTSD risk and vulnerability but also provide a starting point for prediction and intervention studies.

Authors 8

1. Lycia D. de Voogd corresponding Aachen

   Leiden University · Radboud University Nijmegen · Donders Centre for Cognitive Neuroimaging · Donders Institute for Brain, Cognition and Behaviour

   Affiliation as printed

   Donders Institute, Centre for Cognitive Neuroimaging, Radboud University, Nijmegen, the Netherlands; Behavioural Science Institute, Radboud University, Nijmegen, the Netherlands; Institute of Psychology, Leiden University, Leiden, the Netherlands; Leiden Institute for Brain and Cognition, Leiden University, Leiden, the Netherlands. Electronic address: l.d.de.voogd@fsw.leidenuniv.nl

   Donders Institute, Centre for Cognitive Neuroimaging, Radboud University, Nijmegen, the Netherlands; Behavioural Science Institute, Radboud University, Nijmegen, the Netherlands; Institute of Psychology, Leiden University, Leiden, The Netherlands; Leiden Institute for Brain and Cognition (LIBC), Leiden University, Leiden, The Netherlands. Electronic address: l.d.de.voogd@fsw.leidenuniv.nl

2. Mahur Melina Hashemi

   Radboud University Nijmegen · Donders Centre for Cognitive Neuroimaging · Donders Institute for Brain, Cognition and Behaviour

   Affiliation as printed

   Donders Institute, Centre for Cognitive Neuroimaging, Radboud University, Nijmegen, the Netherlands; Behavioural Science Institute, Radboud University, Nijmegen, the Netherlands

3. Wei Zhang

   Washington University in St. Louis

   Affiliation as printed

   Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri

   Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, United States

4. Reinoud Kaldewaij

   Linköping University

   Affiliation as printed

   Center for Social and Affective Neuroscience, Linköping University, Linköping, Sweden; Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden

5. Saskia B.J. Koch

   Radboud University Nijmegen · Donders Centre for Cognitive Neuroimaging · Donders Institute for Brain, Cognition and Behaviour

   Affiliation as printed

   Donders Institute, Centre for Cognitive Neuroimaging, Radboud University, Nijmegen, the Netherlands

6. Vanessa Anna van Ast

   University of Amsterdam

   Affiliation as printed

   Department of Clinical Psychology, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Brain and Cognition, University of Amsterdam, Amsterdam, the Netherlands

7. Floris Klumpers

   Radboud University Nijmegen · Donders Centre for Cognitive Neuroimaging · Donders Institute for Brain, Cognition and Behaviour

   Affiliation as printed

   Donders Institute, Centre for Cognitive Neuroimaging, Radboud University, Nijmegen, the Netherlands; Behavioural Science Institute, Radboud University, Nijmegen, the Netherlands

8. Karin Roelofs

   Radboud University Nijmegen · Donders Centre for Cognitive Neuroimaging · Donders Institute for Brain, Cognition and Behaviour

   Affiliation as printed

   Donders Institute, Centre for Cognitive Neuroimaging, Radboud University, Nijmegen, the Netherlands; Behavioural Science Institute, Radboud University, Nijmegen, the Netherlands