Progress in research on effects of chronic stress on brain structure and function

Abstract

As a cumulative and persistent form of stress, chronic stress has been shown to have a profound impact on the structure and function of the human brain. This article reviews the neurobiological mechanisms of chronic stress acting on the brain and its key role in mood and cognitive dysfunction. Long-term activation of the hypothalamic-pituitary-adrenal (HPA) axis leads to sustained elevation of cortisol, disrupting negative feedback regulation and causing neurotoxic damage to key brain regions such as the hippocampus and prefrontal cortex. At the same time, chronic stress can interfere with the neurotransmitter system, especially the dopamine and serotonin pathways, leading to emotional instability, anhedonia, and decreased cognitive flexibility. In addition, synaptic plasticity and functional remodeling of neural networks are also significantly affected, manifested by inhibition of long-term enhancement (LTP), abnormal enhancement of long-term inhibition (LTD), decreased synaptic connectivity, and dysregulation of emotion-cognitive circuits. These mechanisms interact to form a vicious circle that increases the risk of depression, anxiety disorders, and mental illnesses such as post-traumatic stress disorder (PTSD). A deeper understanding of the neural mechanisms of chronic stress not only helps to reveal the brain's adaptation and dysregulation response to stress, but also provides a theoretical basis for early intervention, biomarker identification and treatment strategy development.