At-risk individuals display altered brain activity following stress

Abstract

Stress is a major risk factor for almost all psychiatric disorders, however, the underlying neurobiological mechanisms remain largely elusive. In healthy individuals, a successful stress response involves an adequate neuronal adaptation to a changing environment. This adaptive response may be dysfunctional in vulnerable individuals, potentially contributing to the development of psychopathology. In the current study, we investigated brain responses to emotional stimuli following stress in healthy controls and at-risk individuals. An fMRI study was conducted in healthy male controls (N = 39) and unaffected healthy male siblings of schizophrenia patients (N = 39) who are at increased risk for the development of a broad range of psychiatric disorders. Brain responses to pictures from the International Affective Picture System (IAPS) were measured 33 min after exposure to stress induced by the validated trier social stress test (TSST) or a control condition. Stress-induced levels of cortisol, alpha-amylase, and subjective stress were comparable in both groups. Yet, stress differentially affected brain responses of schizophrenia siblings versus controls. Specifically, control subjects, but not schizophrenia siblings, showed reduced brain activity in key nodes of the default mode network (PCC/precuneus and mPFC) and salience network (anterior insula) as well as the STG, MTG, MCC, vlPFC, precentral gyrus, and cerebellar vermis in response to all pictures following stress. These results indicate that even in the absence of a psychiatric disorder, at-risk individuals display abnormal functional activation following stress, which in turn may increase their vulnerability and risk for adverse outcomes.

Glucocorticoid enhancement of recognition memory via basolateral amygdala-driven facilitation of prelimbic cortex interactions

“…In further support of such functional interactions, we found that GR agonist administration into the PrL after object recognition training induces activity-dependent neuronal activity changes within the aIC and dHPC during the postlearning consolidation period as well as structural changes in spine morphology assessed 24 h later. Our finding that GR agonist-induced enhancement of recognition memory is associated with reduced c-Fos expression, and possibly neuronal activity, of the aIC is in agreement with previous findings indicating reduced aIC neuronal activity after systemic corticosterone treatment following inhibitory avoidance training in rats (55) or after stress-induced glucocorticoid release in human subjects (56). Such reduced aIC activity might be needed to facilitate local consolidation processes, possibly by temporarily increasing the threshold for the detection of salient stimuli (23,57).…”

“…Such reduced aIC activity might be needed to facilitate local consolidation processes, possibly by temporarily increasing the threshold for the detection of salient stimuli (23,57). Alternatively, as the aIC might work as a "switch" between different neural network systems (58), reduced aIC activity could reflect a reallocation of neural resources and therefore disinhibition of other brain systems involved in the storage of object information and higher-order cognitive processes (56). By contrast, the GR agonist administration increased the number of c-Fos-positive pyramidal cells within CA1, without affecting c-Fos expression within the dDG region of the dHPC.…”

Molecular characterization of the stress network in the human brain

“…2 Moreover, acute social stress deactivates the DMN in the aftermath of stress during emotion processing in healthy controls but not in siblings of schizophrenia patients who are at-risk for several psychiatric disorders. 8,9 Yet, the molecular mechanisms underlying differences in brain reactivity to stress in humans remain unknown as access to the tissue of interest in humans is limited.…”

“…2 Moreover, acute social stress deactivates the DMN in the aftermath of stress during emotion processing in healthy controls but not in siblings of schizophrenia patients who are at-risk for several psychiatric disorders. 8,9 Yet, the molecular mechanisms underlying differences in brain reactivity to stress in humans remain unknown as access to the tissue of interest in humans is limited.Nevertheless, stress-related brain regions and networks as identified by fMRI can be further characterized based on transcriptomic signatures. Mapping gene expression atlases of the healthy brain to imaging data allows the identification of the molecular mechanisms underlying imaging phenotypes.…”

Impaired cognitive performance under psycho-social stress in cannabis-dependent males is mediated by attenuated precuneus activity

“…12,16 Impairments in the neural circuits that mediate the acute adaptive response may contribute to reduced access to adaptive coping, such that cognitive functions, including sustained attention and regulatory control, become compromised. 16,17 A growing number of functional imaging studies reported abnormal emotional reactivity and emotion regulation in cannabis users, including abnormal neural reactivity to affective stimuli 18,19 and deficient amygdala downregulation during cognitive reappraisal. 20 However, despite accumulating evidence for altered emotional reactivity and cognitive emotion regulation, it remains unknown whether deficient stress regulation may contribute to cannabis dependence.…”