Springer Nature is making Coronavirus research free. View research | View latest news | Sign up for updates

Association of paraoxonase-1 activity and major depressive disorder in patients with metabolic syndrome

  • 77 Accesses

  • 1 Citations


Associations between metabolic syndrome (MS) and major depressive disorder (MDD) are well documented although the underlying biological mechanisms for this relationship are less studied. Paraoxonase (PON1) is a high-density lipoprotein (HDL)-associated enzyme, with demonstrated evidence of strong antioxidant activity. Oxidative stress has been implicated in the pathophysiology of MS and MDD. PON1 activity has been studied to some extent in patients with MS and less in MDD. The aim of this study was to compare serum PON1 activity in patients with MS and MDD, MS without MDD, and normal control groups in the context of the biological mechanism of the association between MS and MDD. In this case-control study, 67 patients with MS and 25 healthy controls from the hospital–university staff were recruited. All patients and healthy controls were assessed by a semi-structured psychiatric interview. Patients with MDD were diagnosed according to the DSM-IV criteria for MDD. Serum PON1 activity was determined with a spectrophotometric method, and the activity was compared between patients with MS and MDD, with MS but without MDD, and control groups. Serum PON1 activity levels were lower in patients with MS and MDD group compared to those in the patients with MS and without MDD group and control group (69.5 ± 24.2, 84.3 ± 34.6, and 97.1 ± 40.8 U/ml, p = 0.03, respectively). Post hoc analysis showed that PON1 activity was statically significantly lower in the MS with MDD group than in the control group (p = 0.02). Impaired PON1 activity, in the context of enhanced oxidative stress, could be one of the possible underlying biological mechanisms of the MS–MDD association.

This is a preview of subscription content, log in to check access.


  1. 1.

    Grundy SM. Metabolic syndrome: a multiplex cardiovascular risk factor. J Clin Endocrinol Metab. 2007;92(2):399–404.

  2. 2.

    Li WF, Costa LG, Furlong CE. Serum paraoxonase status: a major factor in determining resistance to organophosphates. J Toxicol Environ Health. 1993;40(2–3):337–46.

  3. 3.

    Primo-Parmo SL, Sorenson RC, et al. The human serum paraoxonase/arylesterase gene (PON1) is one member of a multigene family. Genomics. 1996;33(3):498–507.

  4. 4.

    Mackness MI, Mackness B, Durrington PN, et al. Paraoxonase: biochemistry, genetics and relationship to plasma lipoproteins. Curr Opin Lipidol. 1996;7(2):69–76.

  5. 5.

    Mackness MI, Arrol S, Abbott C, et al. Protection of low-density lipoprotein against oxidative modification by high-density lipoprotein associated paraoxonase. Atherosclerosis. 1993;104(1):129–35.

  6. 6.

    Watson AD, Berliner JA, Hama SY, et al. Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low density lipoprotein. J Clin Invest. 1995;96(6):2882–91.

  7. 7.

    Leviev I, James RW. Promoter polymorphisms of human paraoxonase PON1 gene and serum paraoxonase activities and concentrations. Arterioscler Thromb Vasc Biol. 2000;20(2):516–21.

  8. 8.

    Sentí M, Tomás M, Fitó M, et al. Antioxidant paraoxonase 1 activity in the metabolic syndrome. J Clin Endocrinol Metab. 2003;88(11):5422–6.

  9. 9.

    Lawlor DA, Day IN, Gaunt TR, et al. The association of the paraoxonase (PON1) Q192R polymorphism with depression in older women: findings from the British Women’s Heart and Health Study. J Epidemiol Community Health. 2007;61(1):85–7.

  10. 10.

    Sanghera DK, Saha N, Aston CE, et al. Genetic polymorphism of paraoxonase and the risk of coronary heart disease. Arterioscler Thromb Vasc Biol. 1997;17(6):1067–73.

  11. 11.

    Wheeler JG, Keavney BD, Watkins H, et al. Four paraoxonase gene polymorphisms in 11212 cases of coronary heart disease and 12786 controls: meta-analysis of 43 studies. Lancet. 2004;363(9410):689–95.

  12. 12.

    Sarandol A, Sarandol E, Eker SS, et al. Oxidation of apolipoprotein B-containing lipoproteins and serum paraoxonase/arylesterase activities in major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30(6):1103–8.

  13. 13.

    Mackness B, Davies GK, Turkie W, et al. Paraoxonase status in coronary heart disease: are activity and concentration more important than genotype? Arterioscler Thromb Vasc Biol. 2001;21(9):1451–7.

  14. 14.

    World Health Organization. Definition, diagnosis and classification of diabetes mellitus and its complications: report of a WHO Consultation. Part 1: diagnosis and classification of diabetes mellitus. Geneva, Switzerland: World Health Organization; 1999. Available at: Accessed 25 Mar 2015.

  15. 15.

    American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR). 4th ed. Washington: American Psychiatric Association; 2000.

  16. 16.

    Eckerson HW, Wyte MC, La Du BN. The human serum paraoxonase/arylesterase polymorphism. Am J Hum Genet. 1983;35(6):1126–38.

  17. 17.

    Pan A, Keum N, Okereke OI, et al. Bidirectional association between depression and metabolic syndrome: a systematic review and meta-analysis of epidemiological studies. Diabetes Care. 2012;35(5):1171–80.

  18. 18.

    Marazziti D, Rutigliano G, Baroni S, et al. Metabolic syndrome and major depression. CNS Spectr. 2013;19(4):293–304.

  19. 19.

    Whaley-Connell A, McCullough PA, Sowers JR. The role of oxidative stress in the metabolic syndrome. Rev Cardiovasc Med. 2011;12(1):21–9.

  20. 20.

    Evans PH. Free radicals in brain metabolism and pathology. Br Med Bull. 1993;49(3):577–87.

  21. 21.

    Wolkowitz OM, Reus VI, Mellon SH. Of sound mind and body: depression, disease, and accelerated aging. Dialogues Clin Neurosci. 2011;13(1):25–39.

  22. 22.

    Paz-Filho G, Licinio J, Wong ML. Pathophysiological basis of cardiovascular disease and depression: a chicken-and-egg dilemma. Rev Bras Psiquiatr. 2010;32(2):181–91.

  23. 23.

    Goldston K, Baillie AJ. Depression and coronary heart disease: a review of the epidemiological evidence, explanatory mechanisms and management approaches. Clin Psychol Rev. 2008;28(2):288–306.

  24. 24.

    Wagner G, Icks A, Redaelli M, Albers B, et al. Association of diabetes type 2 and depression - behavioural and biological aspects. Dtsch Med Wochenschr. 2014;139(8):369–74.

  25. 25.

    Cho KH. Biomedicinal implications of high-density lipoprotein: its composition, structure, functions, and clinical applications. BMB Rep. 2009;42(7):393–400.

  26. 26.

    She ZG, Chen HZ, Yan Y, et al. The human paraoxonase gene cluster as a target in the treatment of atherosclerosis. Antioxid Redox Signal. 2012;16(6):597–632.

  27. 27.

    Gur M, Aslan M, Yildiz A, et al. Paraoxonase and arylesterase activities in coronary artery disease. Eur J Clin Investig. 2006;36(11):779–87.

  28. 28.

    Granér M, James RW, Kahri J, et al. Association of paraoxonase-1 activity and concentration with angiographic severity and extent ofcoronary artery disease. J Am Coll Cardiol. 2006;47(12):2429–35.

  29. 29.

    Garin MC, Kalix B, Morabia A, et al. Small, dense lipoprotein particles and reduced paraoxonase-1 in patients with the metabolic syndrome. J Clin Endocrinol Metab. 2005;90(4):2264–9.

  30. 30.

    Zhou C, Cao J, Shang L, et al. Reduced paraoxonase 1 activity as a marker for severe coronary artery disease. Dis Markers. 2013;35(2):97–103.

  31. 31.

    Martinelli N, Micaglio R, Consoli L, et al. Low levels of serum paraoxonase activities are characteristic of metabolic syndrome and may influence the metabolic-syndrome-related risk of coronary artery disease. Exp Diabetes Res.2012:231502.

  32. 32.

    Gaidukov L, Tawfik DS. The development of human sera tests for HDL-bound serum PON1 and its lipolactonase activity. J Lipid Res. 2007;48(7):1637–46.

  33. 33.

    Kodydková J, Vávrová L, Zeman M, et al. Antioxidative enzymes and increased oxidative stress in depressive women. Clin Biochem. 2009;42(13–14):1368–74.

  34. 34.

    James RW, Leviev I, Righetti A. Smoking is associated with reduced serum paraoxonase activity and concentration in patients with coronary artery disease. Circulation. 2000;101(19):2252–7.

  35. 35.

    Ferré N, Camps J, Fernández-Ballart J, et al. Regulation of serum paraoxonase activity by genetic, nutritional, and lifestyle factors in the general population. Clin Chem. 2003;49(9):1491–7.

  36. 36.

    Seres I, Paragh G, Deschene E, et al. Study of factors influencing the decreased HDL associated PON1 activity with aging. Exp Gerontol. 2004;39(1):59–66.

Download references


We thank the staff at the Cardiology and Psychiatry outpatient clinics for their kind cooperation during the study.

Conflict of interest

The authors report no financial relationships or conflicts of interest regarding the content herein.

Author information

Correspondence to Hatem Ari.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Ari, H., Kayrak, M., Gündüz, M. et al. Association of paraoxonase-1 activity and major depressive disorder in patients with metabolic syndrome. Int J Diabetes Dev Ctries 35, 258–263 (2015).

Download citation


  • Metabolic syndrome
  • Depressive disorder
  • Paraoxonase-1 activity