Perceived threat predicts the neural sequelae of combat stress

Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, The Netherlands.
Molecular Psychiatry (Impact Factor: 14.5). 01/2011; 16(6):664-71. DOI: 10.1038/mp.2010.132
Source: PubMed


Exposure to severe stressors increases the risk for psychiatric disorders in vulnerable individuals, but can lead to positive outcomes for others. However, it remains unknown how severe stress affects neural functioning in humans and what factors mediate individual differences in the neural sequelae of stress. The amygdala is a key brain region involved in threat detection and fear regulation, and previous animal studies have suggested that stress sensitizes amygdala responsivity and reduces its regulation by the prefrontal cortex. In this study, we used a prospective design to investigate the consequences of severe stress in soldiers before and after deployment to a combat zone. We found that combat stress increased amygdala and insula reactivity to biologically salient stimuli across the group of combat-exposed individuals. In contrast, its influence on amygdala coupling with the insula and dorsal anterior cingulate cortex was dependent on perceived threat, rather than actual exposure, suggesting that threat appraisal affects interoceptive awareness and amygdala regulation. Our results demonstrate that combat stress has sustained consequences on neural responsivity, and suggest a key role for the appraisal of threat on an amygdala-centered neural network in the aftermath of severe stress.

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Available from: Guido A van Wingen
    • "This debilitating disorder affects approximately 10% of the population in the United States (Kessler, 2000; Kessler et al., 2005), and carries an economic burden now approximating 85 billion dollars per year (Greenberg et al., 2015). The neurobiology underlying PTSD and related disorders is not well understood (Newport and Nemeroff, 2000), and adding to its complexity is the fact that PTSD can also develop in individuals who simply witness a fearful/traumatic event (Perlman et al., 2011; van Wingen et al., 2011). Unfortunately, there is a considerable gap in our basic understanding of the neurobiological consequences of psychological/emotional stress alone and its influence on mental health of the individual. "
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    ABSTRACT: Background: Animal models capable of differentiating the neurobiological intricacies between physical and emotional stress are scarce. Current models rely primarily on physical stressors (e.g. chronic unpredictable or mild stress, social defeat, learned helplessness), and neglect the impact of psychological stress alone. This is surprising given extensive evidence that a traumatic event needs not be directly experienced to produce enduring perturbations on an individual's health and psychological well-being. Post-traumatic stress disorder (PTSD), a highly debilitating neuropsychiatric disorder characterized by intense fear of trauma-related stimuli, often occurs in individuals that have only witnessed a traumatic event. New method: By modifying the chronic social defeat stress (CSDS) paradigm to include a witness component (witnessing the social defeat of another mouse), we demonstrate a novel behavioral paradigm capable of inducing a robust behavioral syndrome reminiscent of PTSD in emotionally stressed adult mice. Results: We describe the vicarious social defeat stress (VSDS) model that is capable of inducing a host of behavioral deficits that include social avoidance and other depressive- and anxiety-like phenotypes in adult male mice. VSDS exposure induces weight loss and spike in serum corticosterone (CORT) levels. A month after stress, these mice retain the social avoidant phenotype and have an increased CORT response when exposed to subsequent stress. Comparison with existing method(s): The VSDS is a novel paradigm capable of inducing emotional stress by isolating physical stress/confrontation in mice. Conclusions: The VSDS model can be used to study the short- and long-term neurobiological consequences of exposure to emotional stress in mice.
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    • "The design allows for identification of blood-based biomarkers, (epi)genetic analyses and symptom trajectories as this cohort is being followed up at multiple time points up to 10 years post deployment. A small group has been scanned with functional neuroimaging of the brain before and after deployment driving new findings e.g. on the role of the amygdala and glucocorticoid receptor number (Geuze et al., 2012; van Wingen et al., 2011). This special issue contains four studies by Boks et al., van Zuiden et al, Reijnen et al, and Smid et al., published from this cohort. "

    Full-text · Article · Jan 2015 · Psychoneuroendocrinology
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    • "Stressful events have both short-and long-term effects on the brain [1] [2]. Acute and chronic stress-induced brain microstructural changes have been observed in prefrontal areas in rodents [3]. "
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    ABSTRACT: Stressful events can have both short- and long-term effects on the brain. Our recent investigation identified short-term white matter integrity (WMI) changes in 30 subjects soon after the Japanese earthquake. Our findings suggested that lower WMI in the right anterior cingulum (Cg) was a pre-existing vulnerability factor and increased WMI in the left anterior Cg and uncinate fasciculus (Uf) after the earthquake was an acquired sign of postearthquake distress. However, the long-term effects on WMI remained unclear. Here, we examined the 1-year WMI changes in 25 subjects to clarify long-term effects on the WMI. We found differential FAs in the right anterior Cg, bilateral Uf, left superior longitudinal fasciculus (SLF), and left thalamus, suggesting that synaptic enhancement and shrinkage were long-term effects. Additionally, the correlation between psychological measures related to postearthquake distress and the degree of WMI alternation in the right anterior Cg and the left Uf led us to speculate that temporal WMI changes in some subjects with emotional distress occurred soon after the disaster. We hypothesized that dynamic WMI changes predict a better prognosis, whereas persistently lower WMI is a marker of cognitive dysfunction, implying the development of anxiety disorders.
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