A longitudinal study of neurotrophic, oxidative, and inflammatory markers in first-onset depression in midlife women

Abstract

Prospective studies have shown during the years preceding and following menopause, also known as "menopause transition", that midlife women are at higher risk for developing first-onset major depressive disorder (MDD). The biological factors associated with risk and resilience in this population are, however, largely unknown. Considering the growing body of evidence suggesting that inflammation, oxidative stress, and brain-derived neurotrophic factor (BDNF) are associated with the pathophysiology of MDD, we investigated serum levels of protein carbonyl, lipid peroxidation (thiobarbituric acid reactive substances-TBARS), thiol group content, BDNF, 3-nitrotyrosine, and heat shock protein 70 (HSP70) in a longitudinal cohort of first-onset MDD. One hundred and forty-eight women from the Harvard Study of Moods and Cycles, a prospective study of midlife women monitored throughout the transition to menopause, were studied. Within- and between-groups analyses of these peripheral markers were conducted in 37 women who developed and 111 women that did not develop MDD during the 3-year follow-up period. In women who developed MDD, HSP70 and 3-nitrotyrosine were elevated at baseline, whereas TBARS were elevated 6 months prior to development of MDD, as compared to those who did not develop MDD. Within-group analyses showed that HSP70, 3-nitrotyrosine, and BDNF decreased over time, whereas protein carbonyl was elevated only at 12 months prior to development of MDD. In women who did not develop MDD, HSP70 and thiol decreased over time. The development of MDD in midlife women may be associated with a systemic cascade of pro-oxidative and pro-inflammatory events including increased HSP70, 3-nitrotyrosine, protein carbonyl, and lipid peroxidation and decreased BDNF.

Gut Microbiota in Alzheimer’s Disease, Depression, and Type 2 Diabetes Mellitus: The Role of Oxidative Stress

“…Extracellular HSPs, in fact, are able to stimulate an inflammatory response leading to an increased proinflammatory cytokine secretion [84]. The demonstration of high plasmatic concentration of extracellular HSP70 in depressed patients has led to hypothesize that it could play a role in the occurrence of mood disorders [85]. Interestingly, the physiological epithelial HSP tone is influenced by gut microbiota activity and diversity.…”

Natural regulatory IgM‐mediated autoimmune responses directed against malondialdehyde regulate oxidative and nitrosative pathways and coupled with IgM responses to nitroso adducts attenuate depressive and physiosomatic symptoms at the end of term pregnancy

“…Another consequence of elevated iNOS and NO production is peroxynitrite formation, which may lead to increased nitration of proteins, and NO 2 tyrosine formation . NO 2 tyrosine levels are increased in depression and bipolar disorder . Moreover, NO 2 tyrosine is immunogenic and may trigger IgM responses directed against NO 2 tyrosine .…”

“…31 NO 2 tyrosine levels are increased in depression and bipolar disorder. 12,[32][33][34] Moreover, NO 2 tyrosine is immunogenic and may trigger IgM responses directed against NO 2 tyrosine. 35,36 However, there are no data on possible correlations between increased NO production and IgM responses to NO adducts or NO 2 tyrosine.…”

The Role of Oxidative Stress in Common Risk Factors and Mechanisms of Cardio-Cerebrovascular Ischemia and Depression

“…Similar mechanisms involving active OS action also happens in depression. Studies indicate that NOX1-derived ROS induces the oxidation of NMDA receptor 1 (NR1) in the prefrontal cortex to facilitate depressive-like behaviors [75], whereas a longitudinal study suggests a cascade of prooxidative and proinflammatory events in the development of depression [76]. Furthermore, OS acts as a link between ischemic CVD and depression (Figure 1 F).…”