Burhanettin KAYA, Nihal AKDAĞ, Ersin FADILLIOĞLU, Serap TAYCAN ERDOĞAN, Mehmet H EMRE, SÜHEYLA ÜNAL, Ahmet SAYAL, Hasan ERDOĞAN, Ruhcan POLAT

Elements levels and glucose- 6-phosphate dehydrogenase activity in blood of patients with schizophrenia

Amaç: Glukoz-6-fosfat dehidrogenaz (G6PD); nukleotid, indirgenmiş glutatyon, yağ asidi ve kolesterol öncüllerinin sentezlerinde rol alan heksoz monofosfat kaskadının hız kısıtlayıcı enzimidir. Aynı zamanda, fetal dönem sırasında ve sonrasında nöral gelişim ve nörotransmitterler için önemli bir enzimdir. Serumda bulunan elementler nöral gelişim, enzim ve hormonların sentez ve aktiviteleri için gereklidirler. Bu çalışmanın amacı, şizofreni hastaları ve sağlıklı kontrollerin bazı serum element düzeylerini ve G6PD enzim aktivitelerini karşılaştırmaktır. Yöntem: Çalışmaya, 32 şizofreni hastası ile yaş ve cinsiyet açısından eşleştirilmiş 32 sağlıklı kontrol dahil edilmiştir. Bakır, çinko, demir ve magnezyum düzeyleri çifte ışıklandırılmış, döteryum kaynaklı, zemin düzeltmesi yapabilen alevli atomik spektrofotometre ile belirlenmiş; alüminyum ve manganez düzeylerini belirlemek içinse grafit atomizer tüp spektroskop kullanılmıştır. G6PD enzim aktivitesi Glock ve Mclean yöntemiyle değerlendirilmiştir. Bulgular: Analiz sonuçları; G6PD aktivitesi, bakır, demir, magnezyum ve alüminyum düzeylerinin hastalarda kontrol grubuna göre daha yüksek olduğunu, çinko ve manganez düzeylerinin ise tersine düşüş gösterdiğini ortaya koymuştur. Tartışma: Şizofreni hastalarındaki G6PD aktivite yüksekliği, literatürle uyumlu bir bulgu değildir. G6PD aktivitesi ve element düzeyleri ile ilgili bu sonuçların, belirli hormonların, antipsikotik tedavilerin ya da şizofreninin doğrudan etkileri ile ilgili olabileceği düşünülmektedir. Sonuç: Araştırdığımız elementler ve G6PD, antioksidan sistemler için önem taşımaktadır. Bu nedenle, şizofreni hastalarındaki element düzey değişiklikleri antioksidan enzimlerin ve G6PDnin işlevlerinde bozulmaya neden olabilir. Bu alanda daha geniş hasta grupları ile ve ilaç kullanmayan hastalarla yapılacak çalışmalara ihtiyaç vardır.

Şizofreni hastalarında kanda glukoz-6-fosfat dehidrogenaz aktivitesi ve element düzeyleri

Elements levels and glucose-6-phosphate dehydrogenase activity in blood of patients with schizophrenia Objectives: Glucose-6-phosphate dehydrogenase (G6PD) is the rate limiting enzyme of the hexose monophosphate cascade which plays role in the synthesis of nucleotide, reduced glutathion, fatty acid and cholesterol precursors. At the same time, it is an important enzyme for neuronal development during and after fetal life and for neurotransmitters. Serum elements are necessary for neuronal development and synthesis and activity of enzymes and hormones. The aim of this study was to compare serum levels of some elements and G6PD enzyme activity in schizophrenic patients with those in healthy individuals. Methods: This study involved blood serum analysis of 32 schizophrenia patients and 32 age- and sex- matched healthy controls. Copper, zinc, iron, magnesium levels were determined with a double lighted, deuterium sourced, background proof reading fire atomic spectrophotometer and in order to determine aluminum and manganese levels, a graphite tube atomizer spectroscope was used. G6PD enzyme activity was analyzed by the Glock and Mclean Method. Results: This analysis revealed higher levels of G6PD activity, copper, iron, magnesium and aluminum in schizophrenia patients compared to controls, whereas zinc and manganese levels showed a decreasing trend on the contrary. Discussion: The higher levels of G6PD activity in schizophrenic patients is not consistent with the literature in general. It is considered that results on G6PD and element levels may be explained as the effects of specific hormones, antipsychotic medications, or by schizophrenia itself. Conclusion: The elements we investigated and G6PD are important for the antioxidant system. Thus changing levels of elements in patients with schizophrenia may lead to disturbed functions of antioxidant enzymes and G6PD. Further researches on this subject conducted with larger and drug naïve patient groups are needed.

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1. Stone WS, Seidman LJ, Wojcik JD, Green AI. Glucose effects on cognition in schizophrenia. Schizophr Res 2003; 62:93-103.
2. Corpas FJ, García-Salguero L, Peragón JA, Lupianez JA. Kinetic properties of hexose-monophosphate dehyrogenases. I. Isolation and partial purification of glucose-6-phosphate dehydrogenase from rat liver and kidney cortex. Life Sci 1995; 56:179-189.
3. Roos D, van Zwieten R, Wijnen JT, Gomez-Gallego F, de Boer M, Stevens D, Pronk-Admiraal CJ, de Rijk T, van Noorden CJ, Weening RS, Vulliamy TJ, Ploem JE, Mason PJ, Bautista JM, Khan PM, Beutler E. Molecular basis and enzymatic properties of glucose 6-phosphate dehydrogenasevolendam, leading to chronic nonspherocytic anemia, granulocyte dysfunction and increased susceptibility to infections. Blood 1999; 94:2955-2962.
4. Verrotti A, Basciani F, Trotta D, Pomilio PM, Morgese G, Chiarelli F. Serum copper, zinc, selenium, glutathione peroxidase and superoxide dismutase levels in epileptic children before and after 1 year of sodium valproate and carbamazepine therapy. Epilepsy Res 2002; 48:71-75.
5. Herran A, Garcia-Unzueta MT, Fernandez-Gonzalez MD, Vazquez-Barquero JL, Alvarez C, Amado JA. Higher levels of serum copper in schizophrenic patients treated with depot neuroleptics. Psychiatry Res 2000; 94:51-58.
6. Kazi S, Ali SS, Furrukh F, Kazi TG, Kazi GH, Kazoo TG. Comparison of metal ions in biological samples of schizophrenic patients and control subjects. Am Clin Lab 2000; 19:8.
7. Janicak PG, Davis JM, Preskorn SH, Ayd FJ, Pavuluri MN, Marder SR (editors). General Principles. In: Principles and Practice of Psychopharmacotherapy. Third ed. Baltimore: Williams & Wilkins, 2001, 1-19.
8. Mental Bozuklukların Tanısal ve Sayımsal El Kitabı, (DSM-IV). Köroğlu E (Çeviri Ed.). 4. Baskı, Ankara: Hekimler Yayın Birliği, 1995 (Book chapter in Turkish).
9. Yüksel N (Editör). Antipsikotik ilaçlar. İçinde: Psikofarmakoloji. Üçüncü Baskı. Ankara: M&N Medikal Nobel, 2007, 47-143 (Book chapter in Turkish).
10. Glock GE, McLean P. Further studies on the properties and assay of glucose 6-phospahate dehydrogenase and 6-phosphogluconate dehydrogenase of rat liver. Biochem J 1953; 55:400-408.
11. Fang YZ, Yang S, Wu G. Free radicals, antioxidants, and nutrition. Nutrition 2000; 18:872-879.
12. Kletzien RP, Harris PK, Foellmi LA. Glucose-6-phosphate dehydrogenase: a housekeeping enzyme subject to tissue- specific regulation by hormones, nutrients, and oxidant stress. FASEB J 1994; 8:174-181.
13. Bocchetta A. Psychotic mania in glucose-6-phosphate dehydrogenase deficient subjects. Ann Gen Hosp Psychiatry 2003; 2:6.
14. Matsuzawa D, Hashimoto K, Hashimoto T, Shimizu E, Watanabe H, Fujita Y, Iyo M. Association study between the genetic polymorphisms of glutathione-releated enzymes and schizophrenia in a Japanese population. Am J Med Genet B Neuropsychiatr Genet 2009; 5:86-94.
15. Novello F, Gumaa JA, McLean P. The pentose phosphate pathway of glucose metabolism. Hormonal and dietary control of the oxidative and non-oxidative reactions of the cycle in liver. Biochem J 1969; 111:713-725.
16. Lehmann HE, Ban TA. The history of the psychopharmacology of schizophrenia. Can J Psychiatry 1997; 42:152-162.
17. Kumar AR, Kurup PA. A hypothalamic digoxin mediated model for conscious and subliminal perception. J Neural Transm 2001; 108:855-868.
18. Akyol O, Herken H, Uz E, Fadillioglu E, Unal S, Söğüt S, Ozyurt H, Savaş HA. The indices of endogenous oxidative and antioxidative processes in plasma from schizophrenic patients. The possible role of oxidant/antioxidant imbalance. Prog Neuropsychopharmacol Biol Psychiatry 2002; 26:995-1005.
19. Ranjekar PK, Hinge A, Hegde MV, Ghate M, Kale A, Sitasawad S, Wagh UV, Debsikdar VB, Mahadik SP. Decreased antioxidant enzymes and membrane essential polyunsaturated fatty acids in schizophrenic and bipolar mood disorder patients. Psychiatry Res 2003; 121:109-122.
20. Padurariu M, Ciobica A, Dobrin I, Stefanescu C. Evaluation of antioxidant enzymes activities and lipid peroxidation in schizophrenic patients treated with typical and atypical antipsychotics. Neurosci Lett 2010; 479:317-320. 21. Pfeiffer CC, Braverman ER. Zinc, the brain and behavior. Biol Psychiatry 1982; 17:513-532.
22. Rahman A, Azad MA, Hossain I, Qusar MM, Bari W, Begum F, Huq SM, Hasnat A. Zinc, manganese, calcium, copper, and cadmium level in scalp hair samples of schizophrenic patients. Biol Trace Elem Res 2009; 127:102-108.
23. Arinola OG, Idonije OB. Status of plasma nitric oxide and non- enzymatic antioxidants before and after antipsychotic treatment in Nigerian patients with schizophrenia. J Res Med Sci 2009; 14:37-42.
24. Johnson S. Micronutrient accumulation and depletion in schizophrenia, epilepsy, autism and Parkinsons disease. Med Hypotheses 2001; 56:641-645.
25. Taneli B. Zinc in Anatolian Population. Ege Tıp Dergisi (Medical Journal of Ege) 2005; 44:1-10.
26. Yanık M, Kocyigit A, Tutkun H, Vural H, Herken H. Plasma manganese, selenium, zinc, copper, and iron concentrations in patients with schizophrenia. Biol Trace Elem Res 2004; 98:109- 117.
27. Heiden A, Frey R, Presslich O, Blasbichler T, Smetana R, Kasper S. Treatment of severe mania with intravenous magnesium sulphate as a supplementary therapy. Pschiatry Res 1999; 89:239-246.
28. Nechifor M. Interactions between magnesium and psychotropic drugs. Magnes Res 2008; 21:97-100.
29. Yao JK, Reddy R, McElhinny LG, van Kammen DP. Effects of haloperidol on antioxidant defense system enzymes in schizophrenia. J Psychiatry Res 1998; 32:385-391.
30. Farooqui AA, Horrocks LA, Farooqui T. Glycerophospholipids in brain: their metabolism incorporation into membranes, functions, and involvement in neurological disorders. Chem Phys Lipids 2000; 106:1-29.
31. Llansola M, Minana MD, Montoliu C, Saez R, Corbalan R, Manzo L, Felipo V. Prenatal exposure to aluminum reduces expression of neuronal nitric oxide synthase and of soluble guanylate cyclase and impairs glutamatergic neurotransmission in rat cerebellum. J Neurochem 1999; 73:712-718.
32. Nayak P, Chatterjee AK. Differential responses pf certain brain phosphoesterases to aluminium in dietary protein adequacy and inadequacy. Food Chem Toxicol 2001; 39:587-592.
33. Hermenegildo C, Saez R, Minoia C. Chronic exposure to aluminium impairs the glutamate-nitric oxide-cyclic GMP pathway in the rat in vivo. Neurochem Int 1999; 34:245-53.
34. Sutherland JE, Greger JL. Kinetics of aluminum disposition after ingestion of low to moderate pharmacological doses of aluminum. Toxicology 1998; 126:115-125.
35. Kanofsky JD, Sandyk R. Magnesium deficiency in chronic schizophrenia. Int J Neuroscience 1991; 61:87-90.
36. Suzuki E, Nakaki T, Nakamura M, Miyaoka H. Plasma nitrate levels in deficit versus non-deficit forms of schizophrenia. J Psychiatry Neurosci 2003; 28:288-292.