A longitudinal study of neurotrophic, oxidative, and inflammatory markers in first-onset depression in midlife women
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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.
KeywordsBDNF Blood Inflammation Major depression Menopause Oxidative stress Women
This work was supported in part by an unrestricted educational Pfizer Fellowship in Women’s Mental Health (Dr. Pasquali). Original funding for the Harvard Study of Moods and Cycles was from NIH Grants R01-MH-50013 and R01-MH-69732 from the National Institute of Mental Health.
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Conflict of interest
Dr. Otto has served as a paid consultant for MicroTransponder Inc., Concert Pharmaceuticals, and ProPhase; provided expert consensus opinion for Otsuka Pharmaceuticals, received royalty support for use of the SIGH-A from ProPhase, and received book royalties from Oxford University Press, Routledge, and Springer. Dr. Cohen has received research support from AstraZeneca Pharmaceuticals, Bayer HealthCare Pharmaceuticals, Bristol-Myers Squibb, Cephalon, Inc., Forest Laboratories, Inc., GlaxoSmithKline, National Institute on Aging, National Institutes of Health, National Institute of Mental Health, Ortho-McNeil Janssen, Pfizer Inc., and Sunovion Pharmaceuticals, Inc. He has done advisory/consulting activities with Noven Pharmaceuticals, and PamLab LLC. Dr. Gelain has received grants from Foundation For Supporting Research of Rio Grande do Sul, Brazil (FAPERGS: PIPG 0427-2551/14-0; and PqG 12099/8), and National Council for Scientific and Technological Development, Brazil (PVE 400437/2013-9). Dr. Moreira has received grants from Foundation For Supporting Research of Rio Grande do Sul, Brazil (FAPERGS: PIPG 0427-2551/14-0; and FAPERGS: PG 12/1060-6), and National Council for Scientific and Technological Development, Brazil (CNPq: 470973/2012-9). Dr. Frey has received grant/research support from Alternative Funding Plan Innovations Award, Brain and Behavior Research Foundation, Canadian Institutes of Health Research, Hamilton Health Sciences Foundation, J.P. Bickell Foundation, Ontario Brain Institute, Ontario Mental Health Foundation, Society for Women’s Health Research, Eli Lilly, and Pfizer, and has received consultant and/or speaker fees from AstraZeneca, Bristol-Myers Squibb, Canadian Psychiatric Association, CANMAT, Lundbeck, Pfizer, Servier, and Sunovion. Drs. Pasquali, Harlow, Soares, and Minuzzi report no financial relationships with commercial interests.
- 12.Cattaneo A, Ferrari C, Uher R, Bocchio-Chiavetto L, Riva MA, MRC ImmunoPsychiatry Consortium, Pariante CM (2016) Absolute measurements of macrophage migration inhibitory factor and interleukin-1-β mrna levels accurately predict treatment response in depressed patients. Int J Neuropsychopharmacol 19. doi: 10.1093/ijnp/pyw045 CrossRefGoogle Scholar
- 21.Frey BN, Andreazza AC, Houenou J, Jamain S, Goldstein BI, Frye MA, Leboyer M, Berk M, Malhi GS, Lopez-Jaramillo C, Taylor VH, Dodd S, Frangou S, Hall GB, Fernandes BS, Kauer-Sant’Anna M, Yatham LN, Kapczinski F, Young LT (2013) Biomarkers in bipolar disorder: a positional paper from the international society for bipolar disorders biomarkers task force. Aust N Z J Psychiatry 47:321–332CrossRefGoogle Scholar
- 24.Grunwald MS, Ligabue-Braun R, Souza CS, Verli H, Gelain DP, Moreira JCF (2017) Putative model for heat shock protein 70 complexation with receptor of advanced glycation end products through fluorescence proximity assays and normal mode analyses. Cell Stress Chaperones 22:99–111CrossRefGoogle Scholar
- 46.Scaini G, Comim CM, Oliveira GM, Pasquali MA, Quevedo J, Gelain DP, Moreira JC, Schuck PF, Ferreira GC, Bogo MR, Streck EL (2013) Chronic administration of branched-chain amino acids impairs spatial memory and increases brain-derived neurotrophic factor in a rat model. J Inherit Metab Dis 36:721–730CrossRefGoogle Scholar
- 55.Weissman MM, Bland RC, Canino GJ, Faravelli C, Greenwald S, Hwu HG, Joyce PR, Karam EG, Lee CK, Lellouch J, Lepine JP, Newman SC, Rubio-Stipec M, Wells JE, Wickramaratne PJ, Wittchen H, Yeh EK (1996) Cross-national epidemiology of major depression and bipolar disorder. JAMA 276:293–299CrossRefGoogle Scholar
- 58.Yoshida T, Ishikawa M, Niitsu T, Nakazato M, Watanabe H, Shiraishi T, Shiina A, Hashimoto T, Kanahara N, Hasegawa T, Enohara M, Kimura A, Iyo M, Hashimoto K (2012) Decreased serum levels of mature brain-derived neurotrophic factor (BDNF), but not its precursor proBDNF, in patients with major depressive disorder. PLoS One 7(8):e42676CrossRefGoogle Scholar