Molecular Neurobiology

, Volume 56, Issue 1, pp 141–156 | Cite as

Major Differences in Neurooxidative and Neuronitrosative Stress Pathways Between Major Depressive Disorder and Types I and II Bipolar Disorder

  • Michael MaesEmail author
  • Kamila Landucci Bonifacio
  • Nayara Rampazzo Morelli
  • Heber Odebrecht Vargas
  • Décio Sabbatini Barbosa
  • André F. Carvalho
  • Sandra Odebrecht Vargas Nunes


Accumulating evidence indicates that oxidative and nitrosative stress (O&NS) pathways play a key role in the pathophysiology of bipolar disorder (BD) and major depressive disorder (MDD). However, only a handful of studies have directly compared alterations in O&NS pathways among patients with MDD and BD types I (BPI) and BPII. Thus, the current study compared superoxide dismutase (SOD1), lipid hydroperoxides (LOOH), catalase, nitric oxide metabolites (NOx), malondialdehyde (MDA), and advanced oxidation protein products (AOPP) between mood disorder patients in a clinically remitted state. To this end 45, 23, and 37 participants with BPI, BPII, and MDD, respectively, as well as 54 healthy controls (HCs) were recruited. Z-unit weighted composite scores were computed as indices of reactive oxygen species (ROS) production and nitro-oxidative stress driving lipid or protein oxidation. SOD1, NOx, and MDA were significantly higher in MDD than in the other three groups. AOPP was significantly higher in BPI than in HCs and BPII patients. BPII patients showed lower SOD1 compared to all other groups. Furthermore, MDD was characterized by increased indices of ROS and lipid hydroperoxide production compared to BPI and BPII groups. Indices of nitro-oxidative stress coupled with aldehyde production or protein oxidation were significantly different among the three patient groups (BDII > BDI > MDD). Finally, depressive symptom scores were significantly associated with higher LOOH and AOPP levels. In conclusion, depression is accompanied by increased ROS production, which is insufficiently dampened by catalase activity, thereby increasing nitro-oxidative damage to lipids and aldehyde production. Increased protein oxidation with formation of AOPP appeared to be hallmark of MDD and BPI. In addition, patients with BPII may have protection against the damaging effects of ROS including lipid peroxidation and aldehyde formation. This study suggests that biomarkers related to O&NS could aid in the differentiation of MDD, BPI, and BPII.


Depression Bipolar disorder Oxidative and nitrosative stress Immune Inflammation 



The authors wish to thank the Centre of Approach and Treatment for Smokers, Psychiatric Unit at UEL, Clinical Laboratory of the University Hospital and Laboratory of Research and Graduate College Hospital (LPG), Brazil.

Author Contributions

All authors contributed to the writing up of the paper. The work was designed by SOVN, MM, DSB, and HOV. Data were collected by SOVN and HOV. Laboratory analyses were conducted by KLB, NRM, and DSB. Statistics were performed by MM. AFC revised the manuscript and provided relevant intellectual content. All authors revised and approved the final draft.


This study was supported by Health Sciences Postgraduate Program at Londrina State University, Parana, Brazil (UEL), and Ministry for Science and Technology of Brazil (CNPq). CNPq number 470344/2013-0 and CNPq number 465928/2014-5. MM is supported by a CNPq - PVE fellowship and the Health Sciences Graduate Program fellowship, State University of Londrina.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Michael Maes
    • 1
    • 2
    • 3
    • 4
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  • Kamila Landucci Bonifacio
    • 1
  • Nayara Rampazzo Morelli
    • 1
  • Heber Odebrecht Vargas
    • 1
  • Décio Sabbatini Barbosa
    • 1
  • André F. Carvalho
    • 5
    • 6
  • Sandra Odebrecht Vargas Nunes
    • 1
  1. 1.Health Sciences Graduation Program, Health Sciences CenterState University of LondrinaParanáBrazil
  2. 2.Department of Psychiatry, Faculty of MedicineChulalongkorn UniversityBangkokThailand
  3. 3.Department of PsychiatryMedical University of PlovdivPlovdivBulgaria
  4. 4.IMPACT Strategic Research Centre, School of MedicineDeakin UniversityVicAustralia
  5. 5.Department of PsychiatryUniversity of TorontoTorontoCanada
  6. 6.Centre for Addiction & Mental HealthTorontoCanada

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