Role of the locus coeruleus-noradrenergic system in stress-related psychopathology and resilience: Clinical and pre-clinical evidences

Abstract

Stressful events, from daily stressors to traumatic experiences, are common and occur at any age. Despite the high prevalence of trauma, not everyone develops stress-related disorders like major depressive disorder (MDD) and post-traumatic stress disorder (PTSD), a variation attributed to resilience, the ability to adapt and avoid negative consequences of significant stress. This review examines the locus coeruleus-norepinephrine (LC-NE) system, a critical component in the brain's stress response. It discusses the LC-NE system's anatomical and functional complexity and its role in individual variability in stress responses. How different etiological factors and stress modalities affect the LC-NE system, influencing both adaptive stress responses and psychopathologies, are discussed and supported by evidence from human and animal studies. It also explores molecular and cellular adaptations in the LC that contribute to resilience, including roles of neuropeptide, inflammatory cytokines, and genetic modulation, and addresses developmental and sex differences in stress vulnerability. The need for a multifaceted approach to understand stress-induced psychopathologies is emphasized and pave the way for more personalized interventions for stress-related disorders.