Evaluation of adiponectin and leptin levels and oxidative stress in bipolar disorder patients with metabolic syndrome treated by valproic acid

Abstract

Introduction:

An increased risk for metabolic syndrome (MS) has been described for people with psychotic and mood disorders. The aim of this study was to determine the influence of valproic acid (VPA) treatment on adiponectin, leptin levels and oxidative stress in bipolar disorder (BD).

Methods:

Forty patients with BD receiving VPA monotherapy and 20 healthy control subjects were included in this study. BD patients were divided into two groups with and without MS as group 1 and group 2, respectively. Twenty BD patients diagnosed according to the Diagnostic and Statistical Manual for Mental Disorders (DSM IV) were assessed for MS according to the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP III) criteria. Adiponectin, leptin, protein carbonyls, sulfhydryl (–SH) and malondialdehyde (MDA) levels were measured in 40 BD patients and 20 control subjects.

Results:

Serum adiponectin levels were significantly lower in group 1 patients than in group 2 and control subjects (p<.001). Serum leptin levels were significantly higher in group 1 patients than in group 2 and control subjects (p<.001). Serum –SH levels were significantly lower in group 2 patients than in group 1 (p<.001) and control subjects (p<.05). Serum carbonyl levels were significantly higher in group 1 and group 2 patients than in control subjects (p<.001). Serum MDA levels were significantly higher in group 1 patients than in group 2 and control subjects (p<.001).

Conclusion:

These results provide further evidence that VPA treatment for patients with BD contributed to the metabolic disturbances, such as the decreased serum adiponectin and –SH levels, as well as the increased serum leptin, MDA and carbonyl levels.

Keywords

Bipolar disorder valproic acid metabolic syndrome adipokines oxidative stress

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References

Antonijevic

Murck

Frieboes

et al (1998) Elevated nocturnal profiles of serum leptin in patients with depression. J Psychiatr Res 32: 403–410.

Arita

Kihara

Ouchi

et al (1999) Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 257: 79–83.

Atmaca

Kuloğlu

Tezcan

et al (2002) Serum leptin and cholesterol levels in patients with bipolar disorder. Neuropsychobiology 46: 176–179.

Bakos

Berecz

Degrell

(2004) Effect of atypical antipsychotics on metabolism [in Hungarian]. Neuropsychopharmacol Hung 6: 86–89.

Baptista

Teneud

Contreras

et al (1995) Lithium and body weight gain. Pharmacopsychiatry 28: 35–44.

Cengiz

Yuksel

Seven

(2000) The effects of carbamazepine and valproic acid on the erythrocyte glutathione, glutathione peroxidase, superoxide dismutase and serum lipid peroxidation in epileptic children. Pharmacol Res 41: 423–425.

Chandran

Phillips

Ciaraldi

et al (2003) Adiponectin: More than just another fat cell hormone? Diabetes Care 26: 2442–2450.

Combs

Berg

Obici

et al (2001) Endogenous glucose production is inhibited by the adipose-derived protein Acrp30. J Clin Invest 108: 1875–1881.

DeFronzo

(2004) Pathogenesis of type 2 diabetes mellitus. Med Clin North Am 88: 787–835.

10.

Deuschle

Blum

Eglaro

et al (1996) Plasma leptin in depressed patients and healthy controls. Horm Metab Res 28: 714–717.

11.

Elmslie

Silverstone

Mann

et al (2000) Prevalence of overweight and obesity in bipolar patients. J Clin Psychiatry 61: 179–184.

12.

Fernandes

Dash

Jacka

et al (2016) Leptin in bipolar disorder: A systematic review and meta-analysis. Eur Psychiatry 35: 1–7.

13.

Friedman

(2011) Leptin and the regulation of body weight. Keio J Med 60: 1–9.

14.

Fulop

Tessier

Carpentier

(2006) The metabolic syndrome. Pathol Biol 54:375–386.

15.

Gajwani

(2009) Treatment-refractory bipolar disorder: Classification to aid in clinical management. Expert Opin Pharmacother 10: 1907–1915.

16.

Haddad

Das

Ashfaq

et al (2009) A review of valproate in psychiatric practice. Expert Opin Drug Metab Toxicol 5: 539–551.

17.

Kato

Currier

Gomez

et al (2004) Prevalence of metabolic syndrome in Hispanic and non-Hispanic patients with schizophrenia. Prim Care Companion J Clin Psychiatry 6: 74–77.

18.

Kershaw

Flier

(2004) Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 89: 2548–2556.

19.

Koster

Biemond

Swaak

(1986) Intracellular and extracellular sulfhydryl levels in rheumatoid arthritis. Ann Rheum Dis 45: 44–46.

20.

Kuryszko

Sławuta

Sapikowski

(2016) Secretory function of adipose tissue. Pol J Vet Sci 19: 441–446.

21.

Levine

Garland

Oliver

(1990) Determination of carbonyl content in oxidatively modified proteins. Method Enzymol 186: 464–478.

22.

Loughrey

Young

Lightbody

et al (1994) Oxidative stress in haemodialysis. QJM 87: 679–683.

23.

Huang

Chang

et al (2008) Adiponectin: A biomarker of obesity-induced insulin resistance in adipose tissue and beyond. J Biomed Sci 15: 565–576.

24.

McIntyre

Mancini

Basile

et al (2003) Antipsychotic-induced weight gain: Bipolar disorder and leptin. J Clin Psychopharmacol 23: 323–327.

25.

Maffei

Halaas

Ravussin

et al (1995) Leptin levels in human and rodent: Measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med 1: 1155–1161.

26.

Mansur

Rizzo

Santos

et al (2016) Adipokines, metabolic dysfunction and illness course in bipolar disorder. J Psychiatr Res 74: 63–69.

27.

Meier

Gressner

(2004) Endocrine regulation of energy metabolism: Review of pathobiochemical and clinical chemical aspects of leptin, ghrelin, adiponectin, and resistin. Clin Chem 50: 1511–1525.

28.

Morriss

Mohammed

(2005) Metabolism, lifestyle and bipolar affective disorder. J Psychopharmacol 19: 94–101.

29.

Berk

Dean

et al (2008) Oxidative stress in psychiatric disorders: Evidence base and therapeutic implications. Int J Neuropsychopharmacol 11: 851–876.

30.

Oral

Simha

Ruiz

et al (2002) Leptin replacement therapy for lipodystrophy. N Engl J Med 346: 570–578.

31.

Pylvanen

Knip

Pakarinen

et al (2002) Serum insulin and leptin levels in valproate-associated obesity. Epilepsia 43: 514–517.

32.

Pylvanen

Pakarinen

Knip

et al (2006) Characterization of insulin secretion in valproate-treated patients with epilepsy. Epilepsia 47: 1460–1464.

33.

Sarbijani

Khoshnia

Marjani

(2016) The association between metabolic syndrome and serum levels of lipid peroxidation and interleukin-6 in Gorgan. Diabetes Metab Syndr 10 (1 Suppl. 1): S86–S89.

34.

Simiti

Todor

Stoia

et al (2016) Better prognosis in overweight/obese coronary heart disease patients with high plasma levels of leptin. Clujul Med 89: 65–71.

35.

Toalson

Ahmed

Hardy

et al (2004) The metabolic syndrome in patients with severe mental illnesses. Prim Care Companion J Clin Psychiatry 6: 152–158.

36.

Valko

Rhodes

Moncol

et al (2006) Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 160: 1–40.

37.

Vanina

Podolskaya

Sedky

et al (2002) Body weight changes associated with psychopharmacology. Psychiatr Serv 53: 842–847.

38.

Verrotti

Basciani

De Simone

et al (2002) Insulin resistance in epileptic girls who gain weight after therapy with valproic acid. J Child Neurol 17: 256–258.

39.

Verrotti

Scardapane

Franzoni

et al (2008) Increased oxidative stress in epileptic children treated with valproic acid. Epilepsy Res 78: 171–177.

40.

Webber

(2003) Energy balance in obesity. Proc Nutr Soc 62: 539–543.

41.

Yang

Lee

Funahashi

et al (2001) Weight reduction increases plasma levels of an adipose-derived anti-inflammatory protein, adiponectin. J Clin Endocrinol Metab 86: 3815–3819.

42.

Yang

Lee

Funahashi

et al (2002) Plasma adiponectin levels in overweight and obese Asians. Obes Res 10: 1104–1110.