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

  • Matheus A. Pasquali
  • Bernard L. Harlow
  • Claudio N. Soares
  • Michael W. Otto
  • Lee S. Cohen
  • Luciano Minuzzi
  • Daniel P. Gelain
  • Jose Claudio F. Moreira
  • Benicio N. FreyEmail author
Original Paper


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.


BDNF 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.

Compliance with ethical standards

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.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Matheus A. Pasquali
    • 1
    • 2
    • 3
  • Bernard L. Harlow
    • 4
  • Claudio N. Soares
    • 5
  • Michael W. Otto
    • 6
  • Lee S. Cohen
    • 7
  • Luciano Minuzzi
    • 1
    • 2
    • 8
  • Daniel P. Gelain
    • 3
  • Jose Claudio F. Moreira
    • 3
  • Benicio N. Frey
    • 1
    • 2
    • 8
    Email author
  1. 1.Women’s Health Concerns ClinicSt. Joseph’s Healthcare HamiltonHamiltonCanada
  2. 2.Mood Disorders ProgramSt. Joseph’s Healthcare HamiltonHamiltonCanada
  3. 3.Centro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, Instituto de Ciências Básicas da SaúdeUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  4. 4.Department of EpidemiologyBoston University School of Public HealthBostonUSA
  5. 5.Department of PsychiatryQueen’s University School of MedicineKingstonCanada
  6. 6.Department of Psychological and Brain SciencesBoston UniversityBostonUSA
  7. 7.Center for Women’s Mental Health Department of Psychiatry, Massachusetts General HospitalBostonUSA
  8. 8.Department of Psychiatry and Behavioural NeurosciencesMcMaster UniversityHamiltonCanada

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