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.

Highlights

  • Stress increases the risk for almost all psychiatric disorders [1]

  • This study investigated the effects of stress on subsequent brain responses in healthy controls and unaffected siblings of schizophrenia patients

  • We found that controls and siblings display large differences in brain activity in response to neutral and emotional pictures half an hour after acute stress, even though the endocrine, subjective, and autonomic stress responses were comparable

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Summary

Introduction

Stress increases the risk for almost all psychiatric disorders [1]. It is thought that a maladaptive response to stress may impair an individual’s capacity to deal with a demanding environment and that this contributes to the risk for psychopathology [2]. Acute stress rapidly facilitates threat detection and habitual behavior, but inhibits the ability to focus attention and make complex decisions. These types of behavior are accompanied by increased activity within the default mode network (DMN) [6] and salience network (SN) [7]. In the aftermath of stress, the stress hormone cortisol plays a major role in the normalization in emotional reactivity with concomitant decreases in the SN [5, 8,] and DMN [9] This dynamic shift in brain functioning during and following stress is hypothesized to underlie an adaptive stress response. Studies investigating the effects of stress on the brain of at-risk individuals are relatively scarce

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