Absence of default mode downregulation in response to a mild psychological stressor marks stress-vulnerability across diverse psychiatric disorders

Neuroimage Clin. 2020:25:102176. doi: 10.1016/j.nicl.2020.102176. Epub 2020 Jan 11.

Abstract

Clinically, it is well-established that vulnerability to stress is a common feature across a broad spectrum of psychiatric disorders. However, this link has been mechanistically studied almost exclusively in patients with so-called stress-related disorders such as depression and anxiety. To probe transdiagnostic mechanisms, we set out to study the acute stress response across a broader range of psychiatric disorders taking a large-scale brain network perspective. We investigated the brain's response to a mild, experimentally well-controlled psychological stressor in the form of an aversive movie. We studied 168 patients with stress-related and/or neurodevelopmental disorders (including comorbidity) and 46 control subjects. We focused on three networks that have a central role in the brain's stress response and are affected in a wide range of psychiatric disorders: the salience network (SN), default mode network (DMN) and frontoparietal network (FPN). Our results support an increased vulnerability to stress across all patients, indicated by a higher subjective stress level at baseline and follow-up compared to matched controls. At the brain systems level, the stress response was characterized by a relatively decreased FPN connectivity and an absence of a decrease in the within DMN connectivity across all disorders compared to controls. At the neurocognitive level, these findings may reflect a diminished top-down control and a tendency to more pronounced (negative) self-referential processing. Besides these shared aspects of the maladaptive stress response, we also discuss indications for disorder-specific aspects. Taken together, our results emphasize the importance of investigating the mechanistic underpinnings of psychiatric disorders transdiagnostically as recently done in neurogenetics.

Keywords: Default; Frontoparietal; Network; Salience; Stress; fMRI.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anxiety Disorders / diagnostic imaging
  • Anxiety Disorders / epidemiology
  • Anxiety Disorders / physiopathology*
  • Attention Deficit Disorder with Hyperactivity / diagnostic imaging
  • Attention Deficit Disorder with Hyperactivity / epidemiology
  • Attention Deficit Disorder with Hyperactivity / physiopathology*
  • Autism Spectrum Disorder / diagnostic imaging
  • Autism Spectrum Disorder / epidemiology
  • Autism Spectrum Disorder / physiopathology*
  • Bipolar Disorder / diagnostic imaging
  • Bipolar Disorder / epidemiology
  • Bipolar Disorder / physiopathology*
  • Comorbidity
  • Connectome*
  • Depressive Disorder / diagnostic imaging
  • Depressive Disorder / epidemiology
  • Depressive Disorder / physiopathology*
  • Female
  • Follow-Up Studies
  • Frontal Lobe / diagnostic imaging
  • Frontal Lobe / physiopathology*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Nerve Net / diagnostic imaging
  • Nerve Net / physiopathology*
  • Parietal Lobe / diagnostic imaging
  • Parietal Lobe / physiopathology*
  • Stress, Psychological / diagnostic imaging
  • Stress, Psychological / physiopathology*
  • Young Adult