Distinct Neurobiological Mechanisms of Chronic and Acute Stress in Major Depressive Disorder: A Review

Chronic and acute stress are well-known risk factors for major depressive disorder (MDD), yet their distinct neurobiological mechanisms remain incompletely understood. Acute stress disorder (ASD) is most prevalent in adolescents and young adults (ages 15-25), while chronic stress is most common in middle-aged individuals (30-50), with higher rates among women. This review synthesizes current evidence to contrast the effects of acute stress, which is the transient prefrontal-amygdala decoupling and executive dysfunction, with chronic stress, which promotes sustained neuroinflammation, HPA axis dysregulation, and structural brain changes. Key findings demonstrate that acute stress impairs "cool" executive functions (working memory, cognitive flexibility) via amygdala-prefrontal circuit disruption, while chronic stress induces hippocampal atrophy and peripheral immune activation through glucocorticoid resistance and BBB (blood-brain barrier) permeability. Despite these advances, limitations exist, such as the insufficient direct evidence linking specific neural pathways to cognitive deficits.