How stress physically re-shapes the brain: Impact on brain cell shapes, numbers and connections in psychiatric disorders

Neurosci Biobehav Rev. 2021 May;124:193-215. doi: 10.1016/j.neubiorev.2021.01.025. Epub 2021 Feb 5.


Severe stress is among the most robust risk factors for the development of psychiatric disorders. Imaging studies indicate that life stress is integral to shaping the human brain, especially regions involved in processing the stress response. Although this is likely underpinned by changes to the cytoarchitecture of cellular networks in the brain, we are yet to clearly understand how these define a role for stress in human psychopathology. In this review, we consolidate evidence of macro-structural morphometric changes and the cellular mechanisms that likely underlie them. Focusing on stress-sensitive regions of the brain, we illustrate how stress throughout life may lead to persistent remodelling of the both neurons and glia in cellular networks and how these may lead to psychopathology. We support that greater translation of cellular alterations to human cohorts will support parsing the psychological sequalae of severe stress and improve our understanding of how stress shapes the human brain. This will remain a critical step for improving treatment interventions and prevention outcomes.

Keywords: Adversity; Amygdala; Bipolar disorder; Cytoarchitecture; Depression; Glia; Hippocampus; Neuron; Prefrontal cortex; Psychiatric disorder; Schizophrenia; Stress.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Brain
  • Cell Shape
  • Humans
  • Mental Disorders*
  • Prefrontal Cortex*
  • Stress, Psychological