Metabolic Brain Disease

, Volume 33, Issue 4, pp 1081–1096 | Cite as

In major affective disorders, early life trauma predict increased nitro-oxidative stress, lipid peroxidation and protein oxidation and recurrence of major affective disorders, suicidal behaviors and a lowered quality of life

  • Juliana Brum Moraes
  • Michael MaesEmail author
  • Chutima Roomruangwong
  • Kamila Landucci Bonifacio
  • Decio Sabbatini Barbosa
  • Heber Odebrecht Vargas
  • George Anderson
  • Marta Kubera
  • Andre F. Carvalho
  • Sandra Odebrecht Vargas Nunes
Original Article


Early life trauma (ELT) may increase the risk towards bipolar disorder (BD) and major depression (MDD), disorders associated with activated neuro-oxidative and neuro-nitrosative stress (O&NS) pathways. It has remained elusive whether ELTs are associated with O&NS and which ELTs are associated with distinct affective disorder phenotypes. This case-control study examined patients with BD (n = 68) and MDD (n = 37) and healthy controls (n = 66). The Child Trauma Questionnaire (CTQ) was used to assess specific ELT. We measured malondialdehyde (MDA), lipid hydroperoxides (LOOH), superoxide dismutase (SOD), catalase, advanced oxidation protein products (AOPP); NO metabolites (NOx), paraoxonase 1 activity, zinc, albumin, high density lipoprotein cholesterol and -SH groups and computed z-unit weighted composite scores. Physical neglect significantly predicts higher z-unit weighted composite scores of LOOH+SOD, LOOH+SOD+NOx, LOOH+SOD+NOx + MDA and LOOH+SOD+NOx + AOPP. Sexual abuse was associated with a significantly lower composite score of zinc+albumin+SH. Emotional abuse was associated with severity of depression and anxiety, number of depressive and manic episodes, alcohol and hypnotics use, lifetime suicidal behavior and lowered quality of life. Sexual abuse was associated with an increased risk towards BD, but not MDD. ELT, especially physical neglect, may drive increased (nitro-)oxidative stress coupled with lipid and protein oxidation, which - together with emotional abuse - may play a role in severity of illness, lowered quality of life and MDD. ELTs are also associated with the onset of BD, but this link did not appear to be related to activated O&NS pathways. These novel findings deserve confirmation in prospective studies.


Depressive disorder Bipolar disorder Child abuse Oxidative stress Antioxidants Suicide 



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 contribution

All authors contributed to the writing up of the paper. The work was designed by SOVN, MM, HOV and JBM. Data were collected by SOVN, JBM and HOV. Laboratory analyses were conducted by KLB and DSB. Statistics were performed by MM. MM, GA, CR, MK and 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.


  1. Aas M, Henry C, Andreassen OA, Bellivier F, Melle I, Etain B (2016) The role of childhood trauma in bipolar disorders. Int J Bipolar Disord 4:2PubMedPubMedCentralCrossRefGoogle Scholar
  2. Afifi TO, Enns MW, Cox BJ, de Graaf R, ten Have M, Sareen J (2007) Child abuse and health-related quality of life in adulthood. J Nerv Ment Dis 195:797–804PubMedCrossRefGoogle Scholar
  3. Agnew-Blais J, Danese A (2016) Childhood maltreatment and unfavourable clinical outcomes in bipolar disorder: a systematic review and meta-analysis. Lancet Psychiatry 3:342–349PubMedCrossRefGoogle Scholar
  4. Aleksandrovskii IA, Poiurovskii MV, Neznamov GG, Seredeniia SB, Krasova EA (1988) Lipid peroxidation in emotional stress and neurotic disorders. Zh Nevropatol Psikhiatr Im S S Korsakova 88:95–101PubMedGoogle Scholar
  5. Al-Fayez GA, Ohaeri JU, Gado OM (2012) Prevalence of physical, psychological, and sexual abuse among a nationwide sample of Arab high school students: association with family characteristics, anxiety, depression, self-esteem, and quality of life. Soc Psychiatry Psychiatr Epidemiol 47:53–66PubMedCrossRefGoogle Scholar
  6. Alvarez MJ, Roura P, Oses A, Foguet Q, Sola J, Arrufat FX (2011) Prevalence and clinical impact of childhood trauma in patients with severe mental disorders. J Nerv Ment Dis 199:156–161PubMedCrossRefGoogle Scholar
  7. American Psychiatric Association (2013) Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5®). American Psychiatric Association Publishing, ArlingtonCrossRefGoogle Scholar
  8. Anderson G, Maes M (2015) Bipolar disorder: role of immune-inflammatory cytokines, oxidative and nitrosative stress and tryptophan catabolites. Curr Psychiatry Rep 17:8PubMedCrossRefGoogle Scholar
  9. Andreazza AC, Kauer-Sant'anna M, Frey BN, Bond DJ, Kapczinski F, Young LT, Yatham LN (2008) Oxidative stress markers in bipolar disorder: a meta-analysis. J Affect Disord 111:135–144PubMedCrossRefGoogle Scholar
  10. Barceloux DG, Barceloux D (1999) Zinc. J Toxicol 2:179–192Google Scholar
  11. Bastos AS, Loureiro AP, de Oliveira TF, Corbi SC, Caminaga RM, Junior CR, Orrico SR (2012) Quantitation of malondialdehyde in gingival crevicular fluid by a high-performance liquid chromatography-based method. Anal Biochem 423:141–146Google Scholar
  12. Bengesser SA, Lackner N, Birner A, Fellendorf FT, Platzer M, Mitteregger A, Unterweger R, Reininghaus B, Mangge H, Wallner-Liebmann SJ, Zelzer S, Fuchs D, McIntyre RS, Kapfhammer HP, Reininghaus EZ (2015) Peripheral markers of oxidative stress and antioxidative defense in euthymia of bipolar disorder--Gender and obesity effects. J Affect Disord 172:367–374PubMedCrossRefGoogle Scholar
  13. Bergink V, Larsen JT, Hillegers MH, Dahl SK, Stevens H, Mortensen PB, Petersen L, Munk-Olsen T (2016) Childhood adverse life events and parental psychopathology as risk factors for bipolar disorder. Transl Psychiatry 6:e929PubMedPubMedCentralCrossRefGoogle Scholar
  14. Berk M, Kapczinski F, Andreazza AC, Dean OM, Giorlando F, Maes M, Yucel M, Gama CS, Dodd S, Dean B, Magalhaes PV, Amminger P, McGorry P, Malhi GS (2011) Pathways underlying neuroprogression in bipolar disorder: focus on inflammation, oxidative stress and neurotrophic factors. Neurosci Biobehav Rev 35:804–817PubMedCrossRefGoogle Scholar
  15. Bernstein DP, Stein JA, Newcomb MD, Walker E, Pogge D, Ahluvalia T, Stokes J, Handelsman L, Medrano M, Desmond D, Zule W (2003) Development and validation of a brief screening version of the Childhood Trauma Questionnaire. Child Abuse Negl 27:169–190PubMedCrossRefGoogle Scholar
  16. Bilici M, Efe H, Koroglu MA, Uydu HA, Bekarolu M, Deger O (2001) Antioxidative enzyme activities and lipid peroxidation in major depression: alterations by antidepressant treatments. J Affect Disord 64:43–51PubMedCrossRefGoogle Scholar
  17. Birnbaum HG, Kessler RC, Kelley D, Ben-Hamadi R, Joish VN, Greenberg PE (2010) Employer burden of mild, moderate, and severe major depressive disorder: mental health services utilization and costs, and work performance. Depress Anxiety 27:78–89PubMedCrossRefGoogle Scholar
  18. Bolton JM, Gunnell D, Turecki G (2015) Suicide risk assessment and intervention in people with mental illness. BMJ 351:h4978PubMedCrossRefGoogle Scholar
  19. Bortolasci CC, Vargas HO, Souza-Nogueira A, Barbosa DS, Moreira EG, Nunes SO, Berk M, Dodd S, Maes M (2014) Lowered plasma paraoxonase (PON)1 activity is a trait marker of major depression and PON1 Q192R gene polymorphism-smoking interactions differentially predict the odds of major depression and bipolar disorder. J Affect Disord 159:23–30PubMedCrossRefGoogle Scholar
  20. Brown NC, Andreazza AC, Young LT (2014) An updated meta-analysis of oxidative stress markers in bipolar disorder. Psychiatry Res 218:61–68PubMedCrossRefGoogle Scholar
  21. Catone G, Marwaha S, Kuipers E, Lennox B, Freeman D, Bebbington P, Broome M (2015) Bullying victimisation and risk of psychotic phenomena: analyses of British national survey data. Lancet Psychiatry 2:618–624PubMedCrossRefGoogle Scholar
  22. Chahine EF (2014) Child Abuse and its Relation to Quality of Life of Male and Female Children. Procedia Soc Behav Sci 159:161–168CrossRefGoogle Scholar
  23. Chelikani P, Fita I, Loewen PC (2004) Diversity of structures and properties among catalases. Cell Mol Life Sci 61:192–208PubMedCrossRefGoogle Scholar
  24. Chowdhury MI, Hasan M, Islam MS, Sarwar MS, Amin MN, Uddin SM, Rahaman MZ, Banik S, Hussain MS, Yokota K, Hasnat A (2017) Elevated serum MDA and depleted non-enzymatic antioxidants, macro-minerals and trace elements are associated with bipolar disorders. J Trace Elem Med Biol 39:162–168PubMedCrossRefGoogle Scholar
  25. Cichoń N, Bijak M, Miller E, Niwald M, Saluk J (2015) Poststroke depression as a factor adversely affecting the level of oxidative damage to plasma proteins during a brain stroke. Oxidative Med Cell Longev 2015:408745CrossRefGoogle Scholar
  26. Coelho R, Viola TW, Walss-Bass C, Brietzke E, Grassi-Oliveira R (2014) Childhood maltreatment and inflammatory markers: a systematic review. Acta Psychiatr Scand 129:180–192PubMedCrossRefGoogle Scholar
  27. Dargel AA, Godin O, Kapczinski F, Kupfer DJ, Leboyer M (2015) C-reactive protein alterations in bipolar disorder: a meta-analysis. J Clin Psychiatry 76:142–150PubMedCrossRefGoogle Scholar
  28. Daruy-Filho L, Brietzke E, Lafer B, Grassi-Oliveira R (2011) Childhood maltreatment and clinical outcomes of bipolar disorder. Acta Psychiatr Scand 124:427–434PubMedCrossRefGoogle Scholar
  29. Dean BB, Gerner D, Gerner RH (2004) A systematic review evaluating health-related quality of life, work impairment, and healthcare costs and utilization in bipolar disorder. Curr Med Res Opin 20:139–154PubMedCrossRefGoogle Scholar
  30. Del-Ben CM, Vilela JAA, Crippa JAS, Hallak JEC, Labate CM, Zuardi AW (2001) Confiabilidade da “Entrevista Clínica Estruturada para o DSM-IV - Versao Clinica” traduzida para o portugues. Rev Bras Psiquiatr 23:156–159CrossRefGoogle Scholar
  31. Depp CA, Mausbach BT, Harmell AL, Savla GN, Bowie CR, Harvey PD, Patterson TL (2012) Meta-analysis of the association between cognitive abilities and everyday functioning in bipolar disorder. Bipolar Disord 14:217–226PubMedPubMedCentralCrossRefGoogle Scholar
  32. Eren I, Nazirogglu M, Demirdass A (2007a) Protective effects of lamotrigine, aripiprazole and escitalopram on depression-induced oxidative stress in rat brain. Neurochem Res 32:1188–1195PubMedCrossRefGoogle Scholar
  33. Eren I, Nazirogglu M, Demirdass A, Celik O, Ugguz AC, Altunbassak A, Ozmen I, Uz E (2007b) Venlafaxine modulates depression-induced oxidative stress in brain and medulla of rat. Neurochem Res 32:497–505PubMedCrossRefGoogle Scholar
  34. Etain B, Henry C, Bellivier F, Mathieu F, Leboyer M (2008) Beyond genetics: childhood affective trauma in bipolar disorder. Bipolar Disord 10:867–876PubMedCrossRefGoogle Scholar
  35. Etain B, Mathieu F, Henry C, Raust A, Roy I, Germain A, Leboyer M, Bellivier F (2010) Preferential association between childhood emotional abuse and bipolar disorder. J Trauma Stress 23:376–383PubMedGoogle Scholar
  36. Fernandes BS, Steiner J, Molendijk ML, Dodd S, Nardin P, Gonzalves CA, Jacka F, Kohler CA, Karmakar C, Carvalho AF, Berk M (2016) C-reactive protein concentrations across the mood spectrum in bipolar disorder: a systematic review and meta-analysis. Lancet Psychiatry 3:1147–1156PubMedCrossRefGoogle Scholar
  37. Fisher HL, Jones PB, Fearon P, Craig TK, Dazzan P, Morgan K, Hutchinson G, Doody GA, McGuffin P, Leff J, Murray RM, Morgan C (2010) The varying impact of type, timing and frequency of exposure to childhood adversity on its association with adult psychotic disorder. Psychol Med 40:1967–1978PubMedPubMedCentralCrossRefGoogle Scholar
  38. Fleck MP, Louzada S, Xavier M, Chachamovich E, Vieira G, Santos L, Pinzon V (2000) Application of the Portuguese version of the abbreviated instrument of quality life WHOQOL-bref. Rev Saude Publica 34:178–183PubMedCrossRefGoogle Scholar
  39. Furlong CE, Holland N, Richter RJ, Bradman A, Ho A, Eskenazi B (2006) PON1 status of farmworker mothers and children as a predictor of organophosphate sensitivity. Pharmacogenet Genomics 16:183–190PubMedGoogle Scholar
  40. Galecki P, Maes M, Florkowski A, Lewinski A, Galecka E, Bienkiewicz M, Szemraj J (2011) Association between inducible and neuronal nitric oxide synthase polymorphisms and recurrent depressive disorder. J Affect Disord 129:175–182PubMedCrossRefGoogle Scholar
  41. Garno JL, Goldberg JF, Ramirez PM, Ritzler BA (2005) Impact of childhood abuse on the clinical course of bipolar disorder. Br J Psychiatry 186:121–125PubMedCrossRefGoogle Scholar
  42. GBD 2015 DALYs and HALE Collaborators (2016) Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 388:1603–1658CrossRefGoogle Scholar
  43. Gomes C, Martinho FC, Barbosa DS, Antunes LS, Póvoa HCC, Baltus THL, Morelli NR, Vargas HO, Nunes SOV, Anderson G, Maes M. (2017) Increased root canal endotoxin levels are associated with chronic apical periodontitis, increased oxidative and nitrosative stress, major depression, severity of depression, and a lowered quality of life. Mol Neurobiol.
  44. Gonzalez Flecha B, Llesuy S, Boveris A (1991) Hydroperoxide-initiated chemiluminescence: an assay for oxidative stress in biopsies of heart, liver, and muscle. Free Radic Biol Med 10:93–100PubMedCrossRefGoogle Scholar
  45. Grassi-Oliveira R, Stein LM, Pezzi JC (2006) Translation and content validation of the Childhood Trauma Questionnaire into Portuguese language. Rev Saude Publica 40:249–255PubMedCrossRefGoogle Scholar
  46. Gutteridge JMC, Halliwell B (1994) Antioxidants in Nutrition, Health and Disease. Oxford University Press, OxfordGoogle Scholar
  47. Hadland SE, Marshall BD, Kerr T, Qi J, Montaner JS, Wood E (2012) Suicide and history of childhood trauma among street youth. J Affect Disord 136:377–380PubMedCrossRefGoogle Scholar
  48. Hamilton M (1959) The assessment of anxiety states by rating. Br J Med Psychol 32:50–55PubMedCrossRefGoogle Scholar
  49. Hanasand M, Omdal R, Norheim KB, Gransson LG, Brede C, Jonsson G (2012) Improved detection of advanced oxidation protein products in plasma. Clin Chim Acta 413:901–906PubMedCrossRefGoogle Scholar
  50. Hayyan M, Hashim MA, AlNashef IM (2016) Superoxide Ion: Generation and Chemical Implications. Chem Rev 116:3029–3085PubMedCrossRefGoogle Scholar
  51. Heim C, Shugart M, Craighead WE, Nemeroff CB (2010) Neurobiological and psychiatric consequences of child abuse and neglect. Dev Psychobiol 52:671–690PubMedCrossRefGoogle Scholar
  52. Henrique IFS, De Micheli D, Lacerda RB, Lacerda LA, Formigoni MLOS (2004) Validacao da versao brasileira do teste de triagem do envolvimento com alcool, cigarro e outras substancias (ASSIST). Rev Assoc Med Bras 5:199–206CrossRefGoogle Scholar
  53. Ho DH, Burch ML, Musall B, Musall JB, Hyndman KA, Pollock JS (2016) Early life stress in male mice induces superoxide production and endothelial dysfunction in adulthood. Am J Physiol Heart Circ Physiol 310:H1267–H1274PubMedPubMedCentralCrossRefGoogle Scholar
  54. Hu ML (1994) Measurement of protein thiol groups and glutathione in plasma. Methods Enzymol 233:380–385PubMedCrossRefGoogle Scholar
  55. Irie M, Asami S, Nagata S, Miyata M, Kasai H (2001) Relationships between perceived workload, stress and oxidative DNA damage. Int Arch Occup Environ Health 74:153–157PubMedCrossRefGoogle Scholar
  56. Jansen K, Cardoso TA, Fries GR, Branco JC, Silva RA, Kauer-Sant'Anna M, Kapczinski F, Magalhaes PV (2016) Childhood trauma, family history, and their association with mood disorders in early adulthood. Acta Psychiatr Scand 134:281–286PubMedCrossRefGoogle Scholar
  57. Kendler KS, Sheth K, Gardner CO, Prescott CA (2002) Childhood parental loss and risk for first-onset of major depression and alcohol dependence: the time-decay of risk and sex differences. Psychol Med 32:1187–1194PubMedGoogle Scholar
  58. Khanzode SD, Dakhale GN, Khanzode SS, Saoji A, Palasodkar R (2003) Oxidative damage and major depression: the potential antioxidant action of selective serotonin re-uptake inhibitors. Redox Rep 8:365–370PubMedCrossRefGoogle Scholar
  59. Köhler CA, Freitas TH, Stubbs B, Maes M, Solmi M, Veronese N, de Andrade NQ, Morris G, Fernandes BS, Brunoni AR, Herrmann N, Raison CL, Miller BJ, Lanctôt KL, Carvalho AF (2017) Peripheral alterations in cytokine and chemokine levels after antidepressant drug treatment for major depressive disorder: systematic review and meta-analysis. Mol Neurobiol.
  60. Kohler CA, Freitas TH, Stubbs B, Maes M, Solmi M, Veronese N, de Andrade NQ, Morris G, Fernandes BS, Brunoni AR, Herrmann N, Raison CL, Miller BJ, Lanctot KL, Carvalho AF (2017b) Peripheral alterations in cytokine and chemokine levels after antidepressant drug treatment for major depressive disorder: systematic review and meta-analysis. Mol NeurobiolGoogle Scholar
  61. Kunz M, Gama CS, Andreazza AC, Salvador M, Cereser KM, Gomes FA, Belmonte-de-Abreu PS, Berk M, Kapczinski F (2008) Elevated serum superoxide dismutase and thiobarbituric acid reactive substances in different phases of bipolar disorder and in schizophrenia. Prog Neuro-Psychopharmacol Biol Psychiatry 32:1677–1681CrossRefGoogle Scholar
  62. Leverich GS, Post RM (2006) Course of bipolar illness after history of childhood trauma. Lancet 367:1040–1042PubMedCrossRefGoogle Scholar
  63. Liu T, Zhong S, Liao X, Chen J, He T, Lai S, Jia Y (2015) A Meta-Analysis of Oxidative Stress Markers in Depression. PLoS One 10:e0138904PubMedPubMedCentralCrossRefGoogle Scholar
  64. Lucca G, Comim CM, Valvassori SS, Réus GZ, Vuolo F, Petronilho F, Dal Pizzol F (2009a) Effects of chronic mild stress on the oxidative parameters in the rat brain. Neurochem Int 54:358–362PubMedCrossRefGoogle Scholar
  65. Lucca G, Comim CM, Valvassori SS, Reus GZ, Vuolo F, Petronilho F, Gavioli EC, Dal-Pizzol F, Quevedo J (2009b) Increased oxidative stress in submitochondrial particles into the brain of rats submitted to the chronic mild stress paradigm. J Psychiatr Res 43:864–869PubMedCrossRefGoogle Scholar
  66. Machado-Vieira R, Andreazza AC, Viale CI, Zanatto V, Cereser VJ, da Silva Vargas R, Kapczinski F, Portela LV, Souza DO, Salvador M, Gentil V (2007) Oxidative stress parameters in unmedicated and treated bipolar subjects during initial manic episode: a possible role for lithium antioxidant effects. Neurosci Lett 421:33–36Google Scholar
  67. Maes M, Vandewoude M, Scharpe S, De Clercq L, Stevens W, Lepoutre L, Schotte C (1991) Anthropometric and biochemical assessment of the nutritional state in depression: evidence for lower visceral protein plasma levels in depression. J Affect Disord 23:25–33PubMedCrossRefGoogle Scholar
  68. Maes M, Delanghe J, Meltzer HY, Scharpe S, D'Hondt P, Cosyns P (1994) Lower degree of esterification of serum cholesterol in depression: relevance for depression and suicide research. Acta Psychiatr Scand 90:252–258PubMedCrossRefGoogle Scholar
  69. Maes M, Smith R, Christophe A, Vandoolaeghe E, Van Gastel A, Neels H, Demedts P, Wauters A, Meltzer HY (1997) Lower serum high-density lipoprotein cholesterol (HDL-C) in major depression and in depressed men with serious suicidal attempts: relationship with immune-inflammatory markers. Acta Psychiatr Scand 95:212–221PubMedCrossRefGoogle Scholar
  70. Maes M, Christophe A, Delanghe J, Altamura C, Neels H, Meltzer HY (1999) Lowered omega3 polyunsaturated fatty acids in serum phospholipids and cholesteryl esters of depressed patients. Psychiatry Res 85:275–291PubMedCrossRefGoogle Scholar
  71. Maes M, Christophe A, Bosmans E, Lin A, Neels H (2000) In humans, serum polyunsaturated fatty acid levels predict the response of proinflammatory cytokines to psychologic stress. Biol Psychiatry 47:910–920PubMedCrossRefGoogle Scholar
  72. Maes M, Yirmyia R, Noraberg J, Brene S, Hibbeln J, Perini G, Kubera M, Bob P, Lerer B, Maj M (2009) The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab Brain Dis 24:27–53PubMedCrossRefGoogle Scholar
  73. Maes M, Mihaylova I, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E (2010) Increased plasma peroxides and serum oxidized low density lipoprotein antibodies in major depression: markers that further explain the higher incidence of neurodegeneration and coronary artery disease. J Affect Disord 125:287–294PubMedCrossRefGoogle Scholar
  74. Maes M, Galecki P, Chang YS, Berk M (2011) A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro)degenerative processes in that illness. Prog Neuro-Psychopharmacol Biol Psychiatry 35:676–692CrossRefGoogle Scholar
  75. Maes M, Kubera M, Leunis JC, Berk M, Geffard M, Bosmans E (2013a) In depression, bacterial translocation may drive inflammatory responses, oxidative and nitrosative stress (O&NS), and autoimmune responses directed against O&NS-damaged neoepitopes. Acta Psychiatr Scand 127:344–354PubMedCrossRefGoogle Scholar
  76. Maes M, Kubera M, Mihaylova I, Geffard M, Galecki P, Leunis JC, Berk M (2013b) Increased autoimmune responses against auto-epitopes modified by oxidative and nitrosative damage in depression: implications for the pathways to chronic depression and neuroprogression. J Affect Disord 149:23–29PubMedCrossRefGoogle Scholar
  77. Marklund S, Marklund G (1974) Involvement of the superoxide dismutase anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47:469–471PubMedCrossRefGoogle Scholar
  78. Marsche G, Frank S, Hrzenjak A, Holzer M, Dirnberger S, Wadsack C, Scharnagl H, Stojakovic T, Heinemann A, Oettl K (2009) Plasma-advanced oxidation protein products are potent high-density lipoprotein receptor antagonists in vivo. Circ Res 104:750–757PubMedPubMedCentralCrossRefGoogle Scholar
  79. Mhillaj E, Morgese MG, Trabace L (2015) Early life and oxidative stress in psychiatric disorders: what can we learn from animal models? Curr Pharm Des 21:1396–1403PubMedCrossRefGoogle Scholar
  80. Miret M, Ayuso-Mateos JL, Sanchez-Moreno J, Vieta E (2013) Depressive disorders and suicide: Epidemiology, risk factors, and burden. Neurosci Biobehav Rev 37:2372–2374PubMedCrossRefGoogle Scholar
  81. Monaghan P, Haussmann MF (2015) The positive and negative consequences of stressors during early life. Early Hum Dev 91:643–647PubMedPubMedCentralCrossRefGoogle Scholar
  82. Moraes JB, Maes M, Barbosa DS, Ferrari TZ, Uehara MK, Carvalho AF, Nunes SO (2017) Elevated C-reactive protein levels in women with bipolar disorder may be explained by a history of childhood trauma, especially sexual abuse, body mass index, and age. CNS Neurol Disord Drug TargetsGoogle Scholar
  83. Moreira EG, Correia DG, Bonifacio KL et al. (2017) Lowered PON1 activities are strongly associated with depression and bipolar disorder, recurrence of (hypo)mania and depression, increased disability and lowered quality of life. World J Biol Psychiatry 30:1–13Google Scholar
  84. Moreno RA, Moreno DH (1998) Escalas de depressao de Montgomery & Asberg (MADRS) e de Hamilton (HAM-D) /Hamilton and Montgomery & Asberg depression rating scales. Rev Psiquiatr Clin 25:262–272Google Scholar
  85. Morris G, Berk M, Klein H, Walder K, Galecki P, Maes M (2017) Nitrosative stress, hypernitrosylation, and autoimmune responses to nitrosylated proteins: new pathways in neuroprogressive disorders including depression and chronic fatigue syndrome. Mol Neurobiol 54(6):4271–4291
  86. Murray CJ, Atkinson C, Bhalla K, Birbeck G, Burstein R, Chou D, U.S. Burden of Disease Collaborators, et al., 2013. The state of US health, 1990-2010: burden of diseases, injuries, and risk factors. JAMA 310:591–608Google Scholar
  87. Nanni V, Uher R, Danese A (2012) Childhood maltreatment predicts unfavorable course of illness and treatment outcome in depression: a meta-analysis. Am J Psychiatry 169:141–151PubMedCrossRefGoogle Scholar
  88. Navarro-Gonzalvez JA, Garcia-Benayas C, Arenas J (1998) Semiautomated measurement of nitrate in biological fluids. Clin Chem 44:679–681PubMedGoogle Scholar
  89. Novick DM, Swartz HA, Frank E (2010) Suicide attempts in bipolar I and bipolar II disorder: a review and meta-analysis of the evidence. Bipolar Disord 12:1–9PubMedPubMedCentralCrossRefGoogle Scholar
  90. Nowak G (2015) Zinc, future mono/adjunctive therapy for depression: Mechanisms of antidepressant action. Pharmacol Rep 67:659–662PubMedCrossRefGoogle Scholar
  91. Nunes SO, Piccoli de Melo LG, Pizzo de Castro MR, Barbosa DS, Vargas HO, Berk M, Maes M (2015) Atherogenic index of plasma and atherogenic coefficient are increased in major depression and bipolar disorder, especially when comorbid with tobacco use disorder. J Affect Disord 172:55–62PubMedCrossRefGoogle Scholar
  92. Ozcan ME, Gulec M, Ozerol E, Polat R, Akyol O (2004) Antioxidant enzyme activities and oxidative stress in affective disorders. Int Clin Psychopharmacol 19:89–95PubMedCrossRefGoogle Scholar
  93. Pacher P, Beckman JS, Liaudet L (2007) Nitric oxide and peroxynitrite in health and disease. Physiol Rev 87:315–424PubMedPubMedCentralCrossRefGoogle Scholar
  94. Pal SN, Dandiya PC (1994) Glutathione as a cerebral substrate in depressive behavior. Pharmacol Biochem Behav 48:845–851PubMedCrossRefGoogle Scholar
  95. Panis C, Herrera ACSA, Victorino VJ, Campos FC, Freitas LF, De Rossi T, Colado Simao AN, Cecchini AL, Cecchini R (2012) Oxidative stress and hematological profiles of advanced breast cancer patients subjected to paclitaxel or doxorubicin chemotherapy. Breast Cancer Res Treat 133:89–97PubMedCrossRefGoogle Scholar
  96. Peet M, Murphy B, Shay J, Horrobin D (1998) Depletion of omega-3 fatty acid levels in red blood cell membranes of depressive patients. Biol Psychiatry 43:315–319PubMedCrossRefGoogle Scholar
  97. Pertsov SS, Balashova TS, Kubatieva AA, Sosnovskii AS, Pirogova GV, Abramov VM (1995) Lipid peroxidation and antioxidant enzymes in rat brain in acute emotional stress: effect of interleukin-1beta. Biull Eksp Biol Med 120:244–247PubMedGoogle Scholar
  98. Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, Currier GW, Melvin GA, Greenhill L, Shen S, Mann JJ (2011) The Columbia-Suicide Severity Rating Scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry 168:1266–1277PubMedPubMedCentralCrossRefGoogle Scholar
  99. do Prado CH, Grassi-Oliveira R, Wieck A, Zaparte A, Filho LD, da Silva Morrone M, Moreira JC, Bauer ME (2016) The impact of childhood maltreatment on redox state: Relationship with oxidative damage and antioxidant defenses in adolescents with no psychiatric disorder. Neurosci Lett 617:173–177PubMedCrossRefGoogle Scholar
  100. Ranjekar PK, Hinge A, Hegde MV, Ghate M, Kale A, Sitasawad S, Wagh UV, Debsikdar VB, Mahadik SP (2003) Decreased antioxidant enzymes and membrane essential polyunsaturated fatty acids in schizophrenic and bipolar mood disorder patients. Psychiatry Res 121:109–122PubMedCrossRefGoogle Scholar
  101. Richter RJ, Jarvik GP, Furlong CE (2008) Determination of paraoxonase 1 status without the use of toxic organophosphate substrates. Circ Cardiovasc Genet 1:147–152PubMedPubMedCentralCrossRefGoogle Scholar
  102. Roy A, Janal M (2005) Family history of suicide, female sex, and childhood trauma: separate or interacting risk factors for attempts at suicide? Acta Psychiatr Scand 112:367–371PubMedCrossRefGoogle Scholar
  103. Runyan D, Wattam C, Ikeda R, Hassan F, Ramiro L (2002) Child abuse and neglect by parents and other caregivers. In: Krug E, Dahlberg LL, Mercy JA, Zwi AB, Lozano R (eds) World report on violence and health. World Health Organization, Geneva,Switzerland, p. 59–86Google Scholar
  104. Sarandol A, Sarandol E, Eker SS, Erdinc S, Vatansever E, Kirli S (2007) Major depressive disorder is accompanied with oxidative stress: short-term antidepressant treatment does not alter oxidative-antioxidative systems. Hum Psychopharmacol 22:67–73PubMedCrossRefGoogle Scholar
  105. Schiavone S, Colaianna M, Curtis L (2015) Impact of early life stress on the pathogenesis of mental disorders: relation to brain oxidative stress. Curr Pharm Des 21:1404–1412PubMedCrossRefGoogle Scholar
  106. Schoedl AF, Costa MC, Mari JJ, Mello MF, Tyrka AR, Carpenter LL, Price LH (2010) The clinical correlates of reported childhood sexual abuse: an association between age at trauma onset and severity of depression and PTSD in adults. J Child Sex Abus 19:156–170PubMedPubMedCentralCrossRefGoogle Scholar
  107. Sfoggia A, Pacheco MA, Grassi-Oliveira R (2008) History of childhood abuse and neglect and suicidal behavior at hospital admission. Crisis 29:154–158PubMedCrossRefGoogle Scholar
  108. Shao Y, Yan G, Xuan Y, Peng H, Huang QJ, Wu R, Xu H (2015) Chronic social isolation decreases glutamate and glutamine levels and induces oxidative stress in the rat hippocampus. Behav Brain Res 282:201–208PubMedCrossRefGoogle Scholar
  109. Sheehan DV, Harnett-Sheehan K, Raj BA (1996) The measurement of disability. Int Clin Psychopharmacol 11:89–95PubMedCrossRefGoogle Scholar
  110. Simcek S, Kaplan I, Uysal C, Yuksel T, Alaca R (2016) The Levels of Cortisol, Oxidative Stress, and DNA Damage in the Victims of Childhood Sexual Abuse: A Preliminary Study. J Child Sex Abus 25:175–184CrossRefGoogle Scholar
  111. Simon NM, Herlands NN, Marks EH, Mancini C, Letamendi A, Li Z, Pollack MH, Van Ameringen M, Stein MB (2009) Childhood maltreatment linked to greater symptom severity and poorer quality of life and function in social anxiety disorder. Depress Anxiety 26:1027–1032PubMedPubMedCentralCrossRefGoogle Scholar
  112. Sivonova M, Zitnanova I, Hlincikova L, Skodacek I, Trebaticka J, Durackova Z (2004) Oxidative stress in university students during examinations. Stress 7:183–188PubMedCrossRefGoogle Scholar
  113. Skevington SM, Lotfy M, O'Connell KA, WHOQOL Group (2004) The World Health Organization's WHOQOL-BREF quality of life assessment: psychometric properties and results of the international field trial. A report from the WHOQOL group. Qual Life Res 13:299–310PubMedCrossRefGoogle Scholar
  114. Sobczak S, Honig A, Christophe A, Maes M, Helsdingen RW, De Vriese SA, Riedel WJ (2004) Lower high-density lipoprotein cholesterol and increased omega-6 polyunsaturated fatty acids in first-degree relatives of bipolar patients. Psychol Med 34:103–112Google Scholar
  115. Song C, Killeen AA, Leonard BE (1994) Catalase, superoxide dismutase and glutathione peroxidase activity in neutrophils of sham-operated and olfactory-bulbectomised rats following chronic treatment with desipramine and lithium chloride. Neuropsychobiology 30:24–28PubMedCrossRefGoogle Scholar
  116. Sosnovskiii AS, Kozlov AV (1992) Increased lipid peroxidation in the rat hypothalamus after short-term emotional stress. Biull Eksp Biol Med 113:486–488CrossRefGoogle Scholar
  117. de Souza FG, Rodrigues MD, Tufik S, Nobrega JN, D'Almeida V (2006) Acute stressor-selective effects on homocysteine metabolism and oxidative stress parameters in female rats. Pharmacol Biochem Behav 85:400–407PubMedCrossRefGoogle Scholar
  118. Swardfager W, Herrmann N, Mazereeuw G, Goldberger K, Harimoto T, Lanctôt KL (2013) Zinc in depression: a meta-analysis. Biol Psychiatry 74:872–878PubMedCrossRefGoogle Scholar
  119. Takizawa R, Maughan B, Arseneault L (2014) Adult health outcomes of childhood bullying victimization: evidence from a five-decade longitudinal British birth cohort. Am J Psychiatry 171:777–784PubMedCrossRefGoogle Scholar
  120. Teicher MH, Samson JA (2013) Childhood maltreatment and psychopathology: A case for ecophenotypic variants as clinically and neurobiologically distinct subtypes. Am J Psychiatry 170:1114–1133PubMedPubMedCentralCrossRefGoogle Scholar
  121. Tsuboi H, Tatsumi A, Yamamoto K, Kobayashi F, Shimoi K, Kinae N (2006) Possible connections among job stress, depressive symptoms, lipid modulation and antioxidants. J Affect Disord 91:63–70PubMedCrossRefGoogle Scholar
  122. Vaccarino V, Brennan ML, Miller AH, Bremner JD, Ritchie JC, Lindau F, Veledar E, Su S, Murrah NV, Jones L, Jawed F, Dai J, Goldberg J, Hazen SL (2008) Association of major depressive disorder with serum myeloperoxidase and other markers of inflammation: a twin study. Biol Psychiatry 64:476–483PubMedPubMedCentralCrossRefGoogle Scholar
  123. Vargas HO, Nunes SO, Pizzo de Castro M, Bortolasci CC, Sabbatini Barbosa D, Kaminami Morimoto H, Venugopal K, Dodd S, Maes M, Berk M (2013) Oxidative stress and lowered total antioxidant status are associated with a history of suicide attempts. J Affect Disord 150:923–930PubMedCrossRefGoogle Scholar
  124. Ventriglio A, Gentile A, Baldessarini RJ, Bellomo A (2015) Early-life stress and psychiatric disorders: epidemiology, neurobiology and innovative pharmacological targets. Curr Pharm Des 21:1379–1387PubMedCrossRefGoogle Scholar
  125. Vilela JA, Crippa JA, Del-Ben CM, Loureiro SR (2005) Reliability and validity of a Portuguese version of the Young Mania Rating Scale. Braz J Med Biol Res 38:1429–1439PubMedCrossRefGoogle Scholar
  126. Walker ER, McGee RE, Druss BG (2015) Mortality in mental disorders and global disease burden implications: a systematic review and meta-analysis. JAMA Psychiatry 72:334–341PubMedPubMedCentralCrossRefGoogle Scholar
  127. WHO ASSIST Working Group (2002) The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST): development, reliability and feasibility. Addiction 97:1183–1194CrossRefGoogle Scholar
  128. Zhang D, Wen XS, Wang XY, Shi M, Zhao Y (2009) Antidepressant effect of Shudihuang on mice exposed to unpredictable chronic mild stress. J Ethnopharmacol 123:55–60PubMedCrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  • Juliana Brum Moraes
    • 1
  • Michael Maes
    • 1
    • 2
    • 3
    • 4
    • 5
    • 6
    Email author
  • Chutima Roomruangwong
    • 2
  • Kamila Landucci Bonifacio
    • 1
  • Decio Sabbatini Barbosa
    • 1
  • Heber Odebrecht Vargas
    • 1
  • George Anderson
    • 7
  • Marta Kubera
    • 8
  • Andre F. Carvalho
    • 9
  • Sandra Odebrecht Vargas Nunes
    • 1
  1. 1.Health Sciences Graduate Program, Health Sciences CenterState University of LondrinaLondrinaBrazil
  2. 2.Department of PsychiatryChulalongkorn UniversityBangkokThailand
  3. 3.Department of PsychiatryMedical University of PlovdivPlovdivBulgaria
  4. 4.RevitalisWaalreThe Netherlands
  5. 5.IMPACT Strategic Research CentreDeakin UniversityGeelongAustralia
  6. 6.IMPACT Strategic Research Centre, School of MedicineDeakin UniversityGeelongAustralia
  7. 7.CRC Scotland & LondonLondonUK
  8. 8.Department of Experimental Neuroendocrinology, Institute of PharmacologyPolish Academy of SciencesKrakowPoland
  9. 9.Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of MedicineFortalezaBrazil

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