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.

Fig. 1

Endocrine, subjective, and autonomic stress measures. Con control, Sib schizophrenia sibling, TSST trier social stress test, AUCi area under the curve with respect to increase. Error bars represent standard error of the mean (SEM)

Fig. 2

Significant clusters showing a group (control/sibling) × stress (stress/no-stress) interaction during the IAPS task after stress induction. Activation maps overlaid onto an anatomical scan in MNI-space (cluster-defining threshold of p < 0.001, cluster probability of p < 0.05, FWE-corrected). Con control, Sib schizophrenia sibling, PCC posterior cingulate cortex, MCC midcingulate cortex, mPFC medial prefrontal cortex, vlPFC ventrolateral prefrontal cortex, STG superior temporal gyrus, L left, R right. X and z coordinates refer to MNI coordinates. *survived Bonferroni correction of p < 0.00125 (p < 0.05/(four groups × ten ROIs)). Error bars represent standard error of the mean (SEM)