AKİF ASDEMİR, MUSTAFA TAYFUN TURAN, Cengiz UYSAL, ESER KILIÇ

Bipolar I bozukluğu için potansiyel bir biyomarker: Serum arjinin vasopressin düzeyleri

Amaç: Bir nöropeptid olan arjinin vasopressin (AVP), davranış ve stres düzenlenmesi üzerinde etkiler gösterir. Bu düzenlenme bipolar bozuklukta hasar görmüştür. Depresif bozuklukların aksine bipolar bozuklukta çok az sayıda çalışma AVP düzeylerini araştırmıştır. Bu çalışmada manik, depresif ve remisyon dönemleri sırasında ve tedaviye yanıttan sonra bipolar I bozukluğu (BB-I) olan hastalarda ve sağlıklı kontrollerde serum AVP düzeylerinin araştırılması amaçlanmıştır. Yöntem: Çalışmaya BB-I olan 67 hasta ve 24 sağlıklı kontrol alınmıştır. Hastalar BBI'in manik, depresif ve remisyon dönemlerindeydi. BB-I olan hastaların üç grubunda ve kontrollerde çalışma başlangıcında serum AVP düzeyleri ölçülmüştür. Daha sonra manik ve depresif atakta olan hastalarda tedaviye yanıttan sonra ikinci kez serum AVP düzeyleri ölçülmüştür. Tedaviye yanıt, manik ve depresif hastalar için sırasıyla Young Mani Derecelendirme Ölçeği ve Hamilton Depresyon Derecelendirme Ölçeği puanlarında %50 azalma olarak tanımlanmıştır. Bulgular: Sağlıklı kontrollerle karşılaştırıldığında BB-I'in manik, depresif ve remisyon dönemlerinin tamamında anlamlı şekilde daha düşük serum AVP düzeyleri çalışmanın temel bulgusudur. Tedaviye yanıt sonrasında depresif BB-I olan hastalarda serum AVP düzeyleri sağlıklı kontrollerin düzeyine yükseldi ve BBI'in remisyon dönemindekinden daha yüksek duruma gelmiştir. Sonuçlar: Serum AVP düzeylerindeki global azalma bipolar bozuklukta görülen bozulmuş nöronal işlevin ve ilerleyici nöronal yıkımın bir göstergesi olabilir. Özellikle majör depresif bozukluktaki artmış AVP düzeyleri dikkate alındığında, serum AVP düzeyleri depresif BB-I'in majör

A potential biomarker for bipolar I disorder: serum arginine vasopressin levels

Objective: The neuropeptide arginine vasopressin (AVP) has effects on behavior and stress regulations which are impaired in bipolar disorder (BD). Only a very limited number of studies have investigated AVP levels in bipolar disorder in contrast to depressive disorders. The study aimed to investigate serum AVP levels during the manic, depressive, or remission periods and after treatment response in patients with bipolar I disorder (BD-I) and healthy controls. Methods: The study consisted of 67 patients with BD-I and 24 healthy controls. The patients were in the manic, depressive, or remission periods of BD-I. Serum AVP levels were assayed in the three groups of patients with BD-I and the controls at the study onset. Then, a second measurement of the AVP levels were carried out in the manic or depressive periods after treatment response. The treatment response was defined as a 50% decrease in the young mania rating scale and the Hamilton Depression Rating Scale scores for manic and depressive episodes, respectively. Results: The main finding was the significantly lower serum AVP levels in BD-I during manic, depressive, or remission periods compared to healthy controls. After-treatment-response serum AVP levels in depressive BD-I patients increased to the levels of healthy controls and became higher than in the remission period of BD-I. Conclusions: The global reduction in serum AVP levels may be an indicator of impaired neuronal function and neuroprogressive deterioration seen in BD. Notably, given the increased AVP levels in major depressive disorder, serum AVP levels may contribute to distinguishing depressive BD-I from major depressive disorder.

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1. Benarroch EE. Oxytocin and vasopressin: social neuropeptides with complex neuromodulatory functions. Neurology 2013; 80:1521-1528.
2. Koshimizu T, Nakamura K, Egashira N, Hiroya-ma M, Nonoguchi H, Tanoue A. Vasopressin V1a and V1b receptors: from molecules to physiolo-gical systems. Physiol Rev 2012; 92:1813-1864.
3. Caldwell HK, Lee HJ, Macbeth AH, Young, WS, 3rd. Vasopressin: behavioral roles of an "original" neuropeptide. Prog Neurobiol 2008; 84:1-24.
4. Frank E, Landgraf R. The vasopressin systemfrom antidiuresis to psychopathology. Eur J Pharmacol 2008; 583:226-242.
5. Rubin LH, Carter CS, Bishop JR, PournajafiNazarloo H, Drogos LL, Hill SK, et al. Reduced levels of vasopressin and reduced behavioral modulation of oxytocin in psychotic disorders. Schizophr Bull 2014; 40:1374-1384.
6. Zelena D. Vasopressin in health and disease with a focus on affective disorders. Cent Nerv Syst Agents Med Chem 2012; 12:286-303.
7. Stanley B, Siever LJ. The Interpersonal Dimension of Borderline Personality Disorder: Toward a Neuropeptide Model. Am J Psychiatry 2010; 167:24-39.
8. de Kloet CS, Vermetten E, Geuze E, Wiegant VM, Westenberg HG. Elevated plasma arginine vasopressin levels in veterans with posttraumatic stress disorder. J Psychiatr Res 2008; 42:192- 198.
9. Task Force on DSM-IV. Diagnostic and Statis-tical Manual of Mental Disorders: DSM-IV-TR. Fourth ed., Washington, DC: American Psychi-atric Association, 2000.
10. Murri MB, Prestia D, Mondelli V, Pariante C, Patti S, Olivieri B, et al. The HPA axis in bipolar disorder: Systematic review and meta-analysis. Psychoneuroendocrinology 2016; 63:327-342.
11. Gold PW, Goodwin FK, Reus VI. Vasopressin in affective illness. Lancet 1978; 1:1233-1236.
12. Sorensen PS, Gjerris A, Hammer M. Cerebrospinal fluid vasopressin in neurological and psychiatric disorders. J Neurol Neurosurg Psychiatry 1985; 48:50-57.
13. Legros JJ, Ansseau M. Increased basal plasma vasopressin-neurophysin in mania. Horm Res 1989; 31:55-58.
14. Linkowski P, Geenen V, Kerkhofs M, Mendlewicz J, Legros JJ. Cerebrospinal fluid neurophysins in affective illness and in schizophrenia. Eur Arch Psychiatry Neurol Sci 1984; 234:162-165.
15. Berrettini WH, Nurnberger JI Jr, Zerbe RL, Gold PW, Chrousos GP, Tomai T. CSF neuropeptides in euthymic bipolar patients and controls. Br J Psychiatry 1987; 150:208-212.
16. Gjerris A, Hammer M, Vendsborg P, Christensen NJ, Rafaelsen OJ. Cerebrospinal fluid vasopressin-changes in depression. Br J Psychiatry 1985; 147:696-701.
17. Penney MD, Levell MJ, Hullin RP. Arginine vasopressin in manic-depressive psychosis. Psychol Med 1987; 17:861-867.
18. Kagerbauer SM, Martin J, Schuster T, Blobner M, Kochs EF, Landgraf R. Plasma oxytocin and vasopressin do not predict neuropeptide concentrations in human cerebrospinal fluid. J Neuroendocrinol 2013; 25:668-673.
19. Carson DS, Howerton CL, Garner JP, Hyde SA, Clark CL, Hardan AY, et al. Plasma vasopressin concentrations positively predict cerebrospinal fluid vasopressin concentrations in human neonates. Peptides 2014; 61:12-16.
20. Turan T, Uysal C, Asdemir A, Kılıç E. May oxytocin be a trait marker for bipolar disorder? Psychoneuroendocrinology 2013; 38:2890-2896. 21. Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 2013; 310:2191-2194.
22. Young RC, Biggs JT, Ziegler VE, Meyer DA. A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry 1978; 133:429-435.
23. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960; 23:56-61.
24. Tang V, Wang J. Oxidative Stress in Bipolar Disorder. Biochem Anal Biochem 2012; S2-002. doi:10.4172/2161-1009.S2-002.
25. Bielau H, Trübner K, Krell D, Agelink MW, Bernstein H, Stauch R, et al. Volume deficits of subcortical nuclei in mood disorders. Eur Arch Psychiatry Clin Neurosci 2005; 255:401-412.
26. Schindler S, Geyer S, Strauss M, Anwander A, Hegerl U, Turner R, et al. Structural studies of the hypothalamus and its nuclei in mood disorders. Psychiatry Res 2012; 201:1-9.
27. Grande I, Berk M, Birmaher B, Vieta E. Bipolar disorder. Lancet; www.thelancet.com Published online September 18, 2015; http://dx.doi.org/10.1016/S0140-6736(15)00241- X
28. Phillips ML, Kupfer DJ. Bipolar disorder diagnosis: Challenges and future directions. Lancet 2013; 381:1663-1671.