Relationship Between the Levels of Nitric Oxide, Asymmetric Dimethylarginine and Neurocognitive Functions in Patients with Bipolar Disorder

Year 2018, Volume: 20 Issue: 2, 33 - 40, 31.10.2018

Betül Kurtses Gürsoy , Nihan Turğut Ayhan Vurmaz

https://doi.org/10.18678/dtfd.444240

Abstract

Aim: The current study aimed to explore the association between cognitive functions and serum nitric oxide (NO), asymmetric dimethylarginine (ADMA) levels in patients with bipolar disorder.

Material and Methods: The study sample was consisted of patients followed by Afyon Kocatepe University Psychiatry Department outpatient clinic. 45 patients diagnosed with bipolar disorder according to DSM-5 criteria and 45 volunteers adjusted for gender, age, and education were included. Sociodemographic Data Form, Hamilton Depression Rating Scale and Young Mania Rating Scale were applied to all participants. Neurocognitive functions were assessed with Test of Verbal Memory Processes, Wisconsin Card Sorting Test (WCST), Stroop Test and Trail-Making Test. Serum NO and ADMA levels were measured using ELISA kit.

Results: It was determined that there was a significant difference (p=0.002) in the family psychiatric family questionnaire between the two matched groups in terms of age, gender and educational status and bipolar disorder in the family of 31% of the patient group. Neuropsychological test scores of patients was statistically lower than control group. Serum ADMA levels of patient group was statistically lower than control group (p=0.001). Statistically significant correlation was found between ADMA levels and spontaneous recall scores (p=0.037), the percent of conceptual level responses (p=0.029), including Stroop Test time scores (p=0.043) and Trail Making Test A time score (p=0.002).

Conclusion: According to the results of present study, in patients with bipolar mood disorder, there is deterioration in areas of cognitive such as memory, learning, attention, processing speed, changing strategy and solving problem. It was determined that the impairment is not associated with serum NO level but the scores of spontaneous recall, the percent of conceptual level responses, time to complete the Stroop Test, Trail Making Test A time were determined that the relationship with serum ADMA level.

Keywords

Bipolar disorder, cognition, nitric oxide, asymmetric dimethylarginine

Bipolar Bozukluk Tanılı Hastalarda Nörokognitif İşlevler ile Nitrik Oksit ve Asimetrik Dimetilarjinin Düzeyleri Arasındaki İlişki

Abstract

Amaç: Bu çalışmada bipolar bozukluk tanısı olan hastalarda bilişsel işlevlerin, serum nitrik oksit (NO) ve asimetrik dimetilarjinin (ADMA) düzeyleri ile ilişkisinin belirlenmesi planlanmıştır.

Gereç ve Yöntemler: Çalışmanın örneklemi Afyon Kocatepe Üniversitesi Tıp Fakültesi Psikiyatri Polikliniği tarafından ayaktan takip edilen, DSM-5’e göre bipolar bozukluk tanısı konulmuş ötimik dönemdeki 45 hasta ile yaş, cinsiyet ve eğitim süresi yönünden eşleştirilmiş 45 sağlıklı gönüllüden oluşturuldu. Çalışmaya katılanlara sosyodemografik veri formu, Hamilton Depresyon Derecelendirme Ölçeği ve Young Mani Derecelendirme Ölçeği uygulandı. Nörokognitif fonksiyonlar Sözel Bellek Süreçleri Testi, Wisconsin Kart Eşleştirme Testi, Stroop Testi ve İz Sürme Testi ile incelendi. Serum NO ve ADMA düzeyleri ELİSA kiti kullanılarak ölçüldü.

Bulgular: Yaş, cinsiyet ve eğitim durumu açısından eşleştirilmiş iki grup arasında ailevi psikiyatrik soygeçmiş sorgulamasında anlamlı farklılık (p=0,002) olduğu ve hasta grubunun %31’inin ailesinde bipolar bozukluk olduğu tesbit edildi. Hasta grubunun nöropsikolojik test sonuçlarının kontrol grubundan istatistiksel olarak anlamlı derecede düşük olduğu bulundu. Serum ADMA düzeyinin ise hasta grubunda kontrol grubuna göre daha düşük düzeyde olduğu gözlendi (p=0,001). ADMA düzeyi ile kendiliğinden hatırlama puanı (p=0,037), kavramsal düzey tepki yüzdesi (p=0,029), Stroop Test puanları (p=0,043) ve İz Sürme A testi süresi (p=0,002) arasında istatistiki olarak anlamlı ilişki olduğu saptandı.

Sonuç: Bu çalışmanın sonuçlarına göre bipolar bozukluk hastalarında bellek, öğrenme, dikkat, işlem hızı, strateji değiştirme, problem çözme gibi bilişsel alanlarda bozulma olduğu fakat bu bozulmanın serum NO düzeyi ile ilişkisi olmadığı fakat kendiliğinden hatırlama, kavramsal tepki yüzdesi, Stroop Testi tamamlama süresi, İz Sürme A testi süresi puanlarının ADMA ile ilişkisi olduğu belirlenmiştir.

Keywords

Bipolar bozukluk, biliş, nitrik oksit, asimetrik dimetilarjinin

References

• 1. Huxley N, Baldessarini RJ. Disability and its treatment in bipolar disorder patients. Bipolar Disord. 2007;9(1–2):183–96.
• 2. Rosa AR, Reinares M, Franco C, Comes M, Torrent C, Sánchez-Moreno J, et al. Clinical predictors of functional outcome of bipolar patients in remission. Bipolar Disord. 2009;11(4):401–9.
• 3. Bonnín CM, Martínez-Arán A, Torrent C, Pacchiarotti I, Rosa AR, Franco C, et al. Clinical and neurocognitive predictors of functional outcome in bipolar euthymic patients: A long-term, follow-up study. J Affect Disord. 2010;121(1–2):156–60.
• 4. Sanchez-Moreno J, Martinez-Aran A, Tabarés-Seisdedos R, Torrent C, Vieta E, Ayuso-Mateos JL. Functioning and disability in bipolar disorder: An extensive review. Vol. 78, Psychotherapy and Psychosomatics. 2009. p. 285–97.
• 5. McKay AP, Tarbuck AF, Shapleske J, McKenna PJ. Neuropsychological function in manic-depressive psychosis. Evidence for persistent deficits in patients with chronic, severe illness. Br J Psychiatry. 1995;167(JULY):51–7.
• 6. Martínez-Arán A, Vieta E, Reinares M, Colom F, Torrent C, Sánchez-Moreno J, et al. Cognitive Function Across Manic or Hypomanic, Depressed, and Euthymic States in Bipolar Disorder. Am J Psychiatry. 2004;161(2):262–70.
• 7. Patel RP, Diczfalusy U, Dzeletovic S, Wilson MT, Darley-Usmar VM. Formation of oxysterols during oxidation of low density lipoprotein by peroxynitrite, myoglobin, and copper. J Lipid Res. 1996;37(11):2361–71.
• 8. Andreazza AC, Kauer-Sant’Anna M, Frey BN, Bond DJ, Kapczinski F, Young LT, et al. Oxidative stress markers in bipolar disorder: A meta-analysis. Vol. 111, Journal of Affective Disorders. 2008. p. 135–44.
• 9. Savaş HA, Herken H, Yürekli M, Uz E, Tutkun H, Zoroǧlu SS, et al. Possible role of nitric oxide and adrenomedullin in bipolar affective disorder. Neuropsychobiology. 2002;45(2):57–61.
• 10. Leiper J, Vallance P. Biological significance of endogenous methylarginines that inhibit nitric oxide synthases. Vol. 43, Cardiovascular Research. 1999. p. 542–8.
• 11. Das I, Khan NS, Puri BK, Hirsch SR. Elevated endogenous nitric oxide synthase inhibitor in schizophrenic plasma may reflect abnormalities in brain nitric oxide production. Neurosci Lett. 1996;215(3):209–11.
• 12. Gergerlioglu HS, Savas HA, Bulbul F, Selek S, Uz E, Yumru M. Changes in nitric oxide level and superoxide dismutase activity during antimanic treatment. Prog Neuro-Psychopharmacology Biol Psychiatry. 2007;31(3):697–702.
• 13. Yanik M, Erel O, Kati M. The relationship between potency of oxidative stress and severity of depression. Acta Neuropsychiatr. 2004;16(4):200–3.
• 14. Selek S, Savas HA, Gergerlioglu HS, Bulbul F, Uz E, Yumru M. The course of nitric oxide and superoxide dismutase during treatment of bipolar depressive episode. J Affect Disord. 2008;107(1–3):89–94.
• 15. Savas HA, Gergerlioglu HS, Armutcu F, Herken H, Yilmaz HR, Kocoglu E, et al. Elevated serum nitric oxide and superoxide dismutase in euthymic bipolar patients: impact of past episodes. World J Biol Psychiatry. 2006;7(1):51–5.
• 16. Selley ML. Increased concentrations of homocysteine and asymmetric dimethylarginine and decreased concentrations of nitric oxide in the plasma of patients with Alzheimer’s disease. Neurobiol Aging. 2003;24(7):903–7.
• 17. Selley ML. Increased (E)-4-hydroxy-2-nonenal and asymmetric dimethylarginine concentrations and decreased nitric oxide concentrations in the plasma of patients with major depression. J Affect Disord. 2004;80(2–3):249–56.
• 18. Aykut D, Tiryaki A, Özkorumak E, Karahan C. Nitric oxide and asymmetrical dimetihylarginine levels in acute mani. Bull Clin Psychopharmacol. 2012;22(1):10–5. 19. Aydemir Ö, Çubukçuoğlu Z, Erdin S, Taş C, Onur E, Berk M. Oxidative stress markers, cognitive functions, and psychosocial functioning in bipolar disorder: an empirical cross-sectional study. Rev Bras Psiquiatr [Internet]. 2014;(AHEAD):0.
• 20. Karakaş S, Alkan S, Can H, Cantez E, Eski R, Genç-Açıkgöz D, et al. BİLNOT Bataryasının güvenirlik ve geçelilik çalışmaları. IX Ulus Psikol Kongresi İstanbul. 1996;
• 21. Spreen O, Strauss EA. Compendium of neuropsychological tests: Administration, norms, and commentary. New York: Oxford University Press; 1991.
• 22. Cavanagh JTO, Van Beck M, Muir W, Blackwood DHR. Case-control study of neurocognitive function in euthymic patients with bipolar disorder: An association with mania. Br J Psychiatry. 2002;180(APR.):320–6.
• 23. Clark L, Iversen SD, Goodwin GM. Sustained attention deficit in bipolar disorder. Br J Psychiatry. 2002;180:313–9.
• 24. Robinson LJ, Ferrier IN. Evolution of cognitive impairment in bipolar disorder: A systematic review of cross-sectional evidence. Vol. 8, Bipolar Disorders. 2006. p. 103–16.
• 25. Robinson LJ, Thompson JM, Gallagher P, Goswami U, Young AH, Ferrier IN, et al. A meta-analysis of cognitive deficits in euthymic patients with bipolar disorder. J Affect Disord. 2006;93(1–3):105–15.
• 26. Torres IJ, Boudreau VG, Yatham LN. Neuropsychological functioning in euthymic bipolar disorder: a meta-analysis. Acta Psychiatr Scand Suppl. 2007;(434):17–26.
• 27. Altshuler LL, Ventura J, Van Gorp WG, Green MF, Theberge DC, Mintz J. Neurocognitive function in clinically stable men with bipolar I disorder or schizophrenia and normal control subjects. Biol Psychiatry. 2004;56(8):560–9.
• 28. Zubieta JK, Huguelet P, O’Neil RL, Giordani BJ. Cognitive function in euthymic Bipolar I Disorder. Psychiatry Res. 2001;102(1):9–20.
• 29. Wingo AP, Harvey PD, Baldessarini RJ. Neurocognitive impairment in bipolar disorder patients: Functional implications. Vol. 11, Bipolar Disorders. 2009. p. 113–25.
• 30. Bora E, P SVAHİ, Z FAİ, Abstract Ö. Bipolar Bozuklukta Bili ş sel Belir lerin Do ğ as ı ve Önemi. 2008;19(1):81–93.
• 31. Kulkarni S, Jain S, Janardhan Reddy YC, Kumar KJ, Kandavel T. Impairment of verbal learning and memory and executive function in unaffected siblings of probands with bipolar disorder. Bipolar Disord. 2010;12(6):647–56.
• 32. Floel A, Poeppel D, Buffalo EA, Braun A, Wu CWH, Seo HJ, et al. Prefrontal Cortex Asymmetry for Memory Encoding of Words and Abstract Shapes. Cereb Cortex. 2004;14(4):404–9.
• 33. Martínez-Arán A, Vieta E, Colom F, Torrent C, Sánchez-Moreno J, Reinares M, et al. Cognitive impairment in euthymic bipolar patients: implications for clinical and functional outcome. Bipolar Disord. 2004;6(3):224–32.
• 34. Öktem Ö. Sözel Bellek Süreçleri Testi (SBST) El Kitabı. Türk Psikologları Derneği Yayınları; 2011.
• 35. Thompson JM, Gallagher P, Hughes JH, Watson S, Gray JM, Ferrier IN, et al. Neurocognitive impairment in euthymic patients with bipolar affective disorder. Br J Psychiatry. 2005;186:32–40.
• 36. Mur M, Portella MJ, Martínez-Arán A, Pifarré J, Vieta E. Neuropsychological profile in bipolar disorder: A preliminary study of monotherapy lithium-treated euthymic bipolar patients evaluated at a 2-year interval. Acta Psychiatr Scand. 2008;118(5):373–81.
• 37. Martinez-Aran a, Vieta E, Torrent C, Sanchez-Moreno J, Goikolea JM, Salamero M, et al. Functional outcome in bipolar disorder: the role of clinical and cognitive factors. Bipolar Disord [Internet]. 2007;9(1–2):103–13.
• 38. Martino DJ, Strejilevich SA, Scápola M, Igoa A, Marengo E, Ais ED, et al. Heterogeneity in cognitive functioning among patients with bipolar disorder. J Affect Disord. 2008;109(1–2):149–56.
• 39. Arts B, Jabben N, Krabbendam L, van Os J. Meta-analyses of cognitive functioning in euthymic bipolar patients and their first-degree relatives. Psychol Med. 2008;38(6):771–85.
• 40. Martino DJ, Marengo E, Igoa A, Scápola M, Ais ED, Perinot L, et al. Neurocognitive and symptomatic predictors of functional outcome in bipolar disorders: A prospective 1 year follow-up study. J Affect Disord. 2009;116(1–2):37–42.
• 41. Bora E, Vahip S, Akdeniz F, Gonul AS, Eryavuz A, Ogut M, et al. The effect of previous psychotic mood episodes on cognitive impairment in euthymic bipolar patients. Bipolar Disord. 2007;9(5):468–77.
• 42. van Gorp WG, Altshuler L, Theberge DC, Wilkins J, Dixon W. Cognitive impairment in euthymic bipolar patients with and without prior alcohol dependence. A preliminary study. Arch Gen Psychiatry. 1998;55(1):41–6.
• 43. Nehra R, Chakrabarti S, Pradhan BK, Khehra N. Comparison of cognitive functions between first- and multi-episode bipolar affective disorders. J Affect Disord. 2006;93(1–3):185–92.
• 44. Garthwaite J, Boulton CL. Nitric oxide signaling in the central nervous system. Annu Rev Physiol. 1995;57:683–706.
• 45. Kielstein JT, Zoccali C. Asymmetric dimethylarginine: A cardiovascular risk factor and a uremic toxin coming of age? Vol. 46, American Journal of Kidney Diseases. 2005. p. 186–202.
• 46. Hoekstra R, Fekkes D, Pepplinkhuizen L, Loonen AJM, Tuinier S, Verhoeven WMA. Nitric oxide and neopterin in bipolar affective disorder. Neuropsychobiology. 2006;54(1):75–81.
• 47. Machado-Vieira R, Andreazza AC, Viale CI, Zanatto V, Cereser V, Vargas R da S, et al. Oxidative stress parameters in unmedicated and treated bipolar subjects during initial manic episode: A possible role for lithium antioxidant effects. Neurosci Lett. 2007;421(1):33–6.