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.

Download full-text


Available from: Guido A van Wingen,
1 Follower
105 Reads
  • Source
    • "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. "
    Psychoneuroendocrinology 01/2015; 51C:441-443. DOI:10.1016/j.psyneuen.2014.11.017 · 4.94 Impact Factor
  • Source
    • "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]. "
    [Show abstract] [Hide abstract]
    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.
    01/2014; 2014(1):180468. DOI:10.1155/2014/180468
  • Source
    • "Repeated stress also leads to increased amygdala activity, observed as increased amygdala activation in humans exposed to chronic or traumatic stress (Shin et al, 1997; Armony et al, 2005; Protopopescu et al, 2005; Ganzel et al, 2007; van Wingen et al, 2011; Bogdan et al, 2012; Dannlowski et al, 2012), and an increase in immediateearly genes' expression in neurons of the basolateral amygdala (BLA) area (comprised of basal, lateral, and basomedial nuclei) upon exposure to a novel stressor (Bhatnagar and Dallman, 1998; Mikics et al, 2008). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Chronic stress leads to heightened affective behaviors, and can precipitate the emergence of depression and anxiety. These disorders are associated with increased amygdala activity. In animal models, chronic stress leads to increased amygdala-dependent behaviors, as well as hyperactivity of amygdala neurons. However, it is not known whether increased excitatory synaptic drive after chronic stress contributes to hyperactivity of basolateral amygdala (BLA; comprised of basal, lateral and accessory basal nucei) neurons. This study tested whether repeated stress causes an increase in excitatory drive of basal amygdala (BA) neurons in vivo, and whether this is correlated with an increase in the number of dendritic spines and a shift in dendritic distribution. Using in vivo intracellular recordings this study found that repeated restraint stress caused an increase in the frequency of spontaneous excitatory synaptic events in vivo correlated with the number of dendritic spines in reconstructed neurons. Furthermore, parallel changes in the kinetics of the synaptic events and the distribution of spines indicated a more prominent functional contribution of synaptic inputs from across the dendritic tree. The shift in spine distribution across the dendritic tree was further confirmed with examination of Golgi-stained tissue. This abnormal physiological drive of BA neurons after repeated stress may contribute to heightened affective responses after chronic stress. A reduction in the impact of excitatory drive in the BA may therefore be a potential treatment for the harmful effects of chronic stress in psychiatric disorders.Neuropsychopharmacology (2013) accepted article preview online, 27 March 2013; doi:10.1038/npp.2013.74.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 03/2013; 38(9). DOI:10.1038/npp.2013.74 · 7.05 Impact Factor
Show more