Stress Molecular Signaling in Interaction With Cognition

Biol Psychiatry. 2025 Feb 15;97(4):349-358. doi: 10.1016/j.biopsych.2024.09.023. Epub 2024 Oct 4.

Abstract

Exposure to stressful life events is associated with a high risk of developing psychiatric disorders with a wide variety of symptoms. Cognitive symptoms in stress-related psychiatric disorders can be particularly challenging to understand, both for those experiencing them and for health care providers. To gain insights, it is important to capture stress-induced structural, epigenomic, transcriptomic, and proteomic changes in relevant brain regions such as the amygdala, hippocampus, locus coeruleus, and prefrontal cortex that result in long-lasting alterations in brain function. In this review, we will emphasize a subset of stress molecular mechanisms that alter neuroplasticity, neurogenesis, and balance between excitatory and inhibitory neurons. Then, we discuss how to identify genetic risk factors that may accelerate stress-driven or stress-induced cognitive impairment. Despite the development of new technologies such as single-cell resolution sequencing, our understanding of the molecular effects of stress in the brain remains to be deepened. A better understanding of the diversity of stress effects in different brain regions and cell types is a prerequisite to open new avenues for mechanism-informed prevention and treatment of stress-related cognitive symptoms.

Keywords: Cognition; Epigenetic; Genetics; Sequencing; Stress; Synaptic plasticity.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain* / metabolism
  • Brain* / physiopathology
  • Cognition* / physiology
  • Cognitive Dysfunction* / genetics
  • Cognitive Dysfunction* / metabolism
  • Cognitive Dysfunction* / physiopathology
  • Humans
  • Neurogenesis / physiology
  • Neuronal Plasticity / physiology
  • Signal Transduction* / physiology
  • Stress, Psychological* / complications
  • Stress, Psychological* / genetics
  • Stress, Psychological* / metabolism
  • Stress, Psychological* / physiopathology