Stressed, Sick, and Sad: Neuroendoimmune Pathways between Subjective Lifetime Stress and Depression

Abstract Disruptions in stress-sensitive biological systems, notably the immune system and hypothalamic-pituitary-adrenal axis, are strongly implicated in depression, and disturbances in these neuroendoimmune systems could reflect potential pathways through which experiences of stress are translated into depression. To characterize the links between stress and depression, the present study investigated whether neuroendoimmune activity mediates the relationship between perceived stress and depressive symptoms in 59 medically healthy adult females with varying levels of depression. Consistent with hypotheses, both greater perceived stress and higher concentrations of the proinflammatory immune marker, interleukin-6 (IL-6), were associated with greater depressive symptoms. Although neuroendoimmune activity did not significantly mediate the relationship between lifetime perceived stress and depressive symptoms, when considered together, elevated concentrations of IL-6 and lower free cortisol mediated the relationship between severity of childhood stress and current depressive symptoms. These findings shed light on how early life stress may be translated into adulthood depression.