Mechanisms underlying stress effects on the brain: Basic concepts and clinical implications

Chronic stress impacts the brain through complex physiological, neurological, and immunological responses. The stress response involves the activation of the sympathetic-adrenal-medullary (SAM) system and the hypothalamic-pituitary-adrenal (HPA) axis, releasing stress hormones like norepinephrine and cortisol. While these responses are adaptive short-term, chronic stress disrupts homeostasis, increasing the risk of cardiovascular diseases, neurodegenerative disorders, and psychiatric conditions such as depression. This dysregulation is linked to persistent neuroinflammation, oxidative stress, and neurotransmitter imbalances involving dopamine and serotonin, impairing neuroplasticity and leading to structural changes in critical brain areas, such as the hippocampus and prefrontal cortex. Moreover, stress affects gene expression, particularly neuroinflammatory pathways, contributing to long-term cognitive function and emotional regulation alterations. Advancements in neuroimaging and molecular techniques, including MRI, PET, and SPECT, hold promise for identifying biomarkers and better understanding stress-induced brain changes. These insights are critical for developing targeted interventions to mitigate the adverse effects of chronic stress on brain health.