Bipolar bozukluk hastalarında beyin kökenli nörotrofik faktör (BDNF) geni Val66Met ve Val66Val polimorfizmi ile hastalık özellikleri ve obsesif kompulsif belirti ilişkisi

Amaç: Bu çalışmada bipolar bozukluk (BB) hastalarında beyin kökenli nörotrofik faktör (brain-derived neuro- trophic factor-BDNF) geni Val66Met ve Val66Val polimorfizmi ile hastalık özellikleri ve obsesif kompulsif belirtiler arasındaki ilişkinin araştırılması amaçlanmıştır. Yöntem: Çalışmamıza klinik görüşme sonucunda DSM-IV-TR tanı ölçütlerine göre BB tanısı konan 106 gönüllü hasta alındı. Tüm katılımcılara Sosyodemografik ve Hastalık Bilgi Formu verildi ve DSM-IV Eksen I Bozuklukları için Yapılandırılmış Klinik Görüşme (Structured Clinical Interview for DSM-IV Axis Disorders-SCID-I), Maudsley Obsesif Kompulsif Soru Listesi, Beck Depresyon Ölçeği ve Beck Anksiyete Ölçeği uygulandı. Hastaların venöz kan örneklerinden DNA izolasyonu yapıldı, elde edilen DNAlar üzerinde PCR-RFLP yöntemi ile BDNF gen polimorfizmine bakıldı. Sonuçlar: Çalışmamızın sonucunda 78 hasta- da BDNF Val66Val, 28 hastada Val66Met polimorfizminin olduğu belirlendi. Val66Val grubundaki hastalarda BB başlama yaşının Val66Met grubundaki hastalara göre daha erken olduğu ve Val66Met grubundaki hastalar ara- sında antidepresan ile tetiklenen mani atağına istatistiksel olarak anlamlı ölçüde daha fazla rastlandığı belirlendi. Obsesif kompulsif bozukluk belirtilerinin varlığı açısından iki grup arasında istatistiksel anlamlılığa sahip bir fark saptanamadı. Tartışma: BBnin bazı özelliklerinin BDNF geni Val66Val/Met polimorfizmi ile ilişkili olduğu düşünül- mektedir. Araştırmamız bu görüşü destekler nitelikte olup daha geniş örneklemlerle yapılacak çalışmalara gerek- sinme vardır.

The relationship between disease characteristics, obsessive compulsive symptoms and brain derived neurotrophic factor (BDNF) gene Val66Met and Val66Val polymorphism in patients with bipolar disorder

Objective: The aim of this study is to investigate the association between brain-derived neurotrophic factor (BDNF) val66met, val66val gene polymorphism and the characteristics of bipolar disorder (BD), obsessive com- pulsive symptoms within patients of BD. Methods: One hundred and six patients, diagnosed with BD according to the DSM-IV-TR criteria, were included in the study. All participants completed a sociodemographic questionnaire and they went through Structured Clinical Interview for DSM-IV Axis Disorders (SCID-I), Maudsley Obsessional Compulsive Questionnaire, Beck Depression Inventory and Beck Anxiety Inventory. DNA isolation was made from patients’ venous blood samples and on these DNA’s BDNF gene polymorphism investigated by PCR-RFLP method. Results: Our results showed that 78 patients had BDNF val66val while 28 patients had val66met poly- morphism. It was found that the patient group with val66val had an earlier age of onset of BD; moreover, in the val66met group, antidepressant induced mania episodes were significantly more frequent. No statistically signify- cant difference was found between the two polymorphism groups with respect to obsessive compulsive symp- toms. Discussion: It has been thought that some characteristics of BD maybe related with the BDNF gene Val66Val/Met polymorphism. Our research partially supports this notion and more studies with larger samples are needed.

___

  • 1. Tsuang MT, Faraone SV. The genetics of mood disorders. The Johns Hopkins series in contem- porary medicine and public health. Baltimore, MD, US: Johns Hopkins University Press. 1990.
  • 2. Birmaher B, Axelson D, Pavuluri M. Bipolar disor- der. M Andres, RV Fred (Eds.), Lewis’s Child and Adolescent Psychiatry A Comprehensive Text- book, fourth ed., 2007, p.513-528.
  • 3. Dick DM, Foroud T, Flury L, Bowman ES, Miller MJ, Rau NL et al. Genomewide linkage analyses of bipolar disorder: a new sample of 250 pedigrees from the National Institute of Mental Health Genetics Initiative. Am J Hum Genet 2003; 73:979.
  • 4. Sklar P, Gabriel SB, McInnis MG, Bennett P, Lim YM, Tsan G, et al. Family-based association study of 76 candidate genes in bipolar disorder: BDNF is a potential risk locus. Brain-derived neurotrophic factor. Mol Psychiatry 2002; 7:579- 593.
  • 5. McInnes LA, Escamilla MA, Service SK, Reus VI, Leon P, Silva S, et al. A complete genome screen for genes predisposing to severe bipolar disorder in two Costa Rican pedigrees. Proc Natl Acad Sci U S A. 1996; 93:13060-13065.
  • 6. Detera-Wadleigh SD, Badner JA, Berrettini WH, Yoshikawa T, Goldin LR, Turner G, et al. A high- density genome scan detects evidence for a bipolar-disorder susceptibility locus on 13q32 and other potential loci on 1q32 and 18p11.2. Proc Natl Acad Sci USA 1999; 96:5604-5609.
  • 7. Muller DJ, de Luca V, Sicard T, King N, Strauss J, Kennedy JL. Brain-derived neurotrophic factor (BDNF) gene and rapid-cycling bipolar disorder: family-based association study. Br J Psychiatry 2006; 189:317-323.
  • 8. Neves-Pereira M, Mundo E, Muglia P, King N, Macciardi F, Kennedy JL. The brain-derived neurotrophic factor gene confers susceptibility to bipolar disorder: evidence from a family-based association study. Am J Hum Genet 2002; 71:651-655.
  • 9. Geller B, Badner JA, Tillman R, Christian SL, Bolhofner K, Cook EH. Linkage disequilibrium of the brain-derived neurotrophic factor Val66Met polymorphism in children with a prepubertal and early adolescent bipolar disorder phenotype. Am J Psychiatry 2004; 161:1698-1700.
  • 10. Hong CJ, Huo SJ, Yen FC, Tung CL, Pan GM, Tsai SJ. Association study of a brain-derived neurotrophic-factor genetic polymorphism and mood disorders, age of onset and suicidal be- havior. Neuropsychobiology. 2003; 48:186-189.
  • 11. Nakata K, Ujike H, Sakai A, Uchida N, Nomura A, Imamura T, et al. Association study of the brain-derived neurotrophic factor (BDNF) gene with bipolar disorder. Neurosci Let 2003; 337:17- 20.
  • 12. Kunugi H, Iijima Y, Tatsumi M, Yoshida M, Hashimoto R, Kato T, et al. No association be- tween the Val66Met polymorphism of the brain- derived neurotrophic factor gene and bipolar disorder in a Japanese population: a multicenter study. Biol Psychiatry. 2004; 56:376-378.
  • 13. Oswald P, Del-Favero J, Massat I, Souery D, Claes S, Van Broeckhoven C, et al. Non-repli- cation of the brain-derived neurotrophic factor (BDNF) association in bipolar affective disorder: a Belgian patient-control study. Am J Med Genet B Neuropsychiatr Genet 2004; 129:34-35.
  • 14. Neves-Pereira M, Cheung JK, Pasdar A, Zhang F, Breen G, Yates P, et al. BDNF gene is a risk factor for schizophrenia in a Scottish population. Mol Psychiatry 2005; 10:208-212.
  • 15. Hall D, Dhilla A, Charalambous A, Gogos JA, Karayiorgou M. Sequence variants of the brain- derived neurotrophic factor (BDNF) gene are strongly associated with obsessive-compulsive disorder. Am J Hum Genet 2003; 73:370-376.
  • 16. Hemmings SM, Kinnear CJ, Van der Merwe L, Lochner C, Corfield VA, Moolman-Smook JC, et al. Investigating the role of the brain-derived neurotrophic factor (BDNF) val66met variant in obsessive-compulsive disorder (OCD). World J Biol Psychiatry 2008; 9:126-134.
  • 17. Rocha FF, Malloy-Diniz L, Lage NV, Correa H. Positive association between MET allele (BDNF Val66Met polymorphism) and obsessive-compul- sive disorder. Rev Bras Psiquiatr 2010; 32:323- 324.
  • 18. Katerberg H, Lochner C, Cath DC, de Jonge P, Bochdanovits Z, Moolman-Smook JC, et al. The role of the brain-derived neurotrophic factor (BDNF) val66met variant in the phenotypic expression of obsessive-compulsive disorder (OCD). Am J Med Genet B Neuropsychiatr Genet 2009; 150:1050-1062.
  • 19. Chen YW, Dilsaver SC. Comorbidity of panic dis- order in bipolar illness: evidence from the Epi- demiologic Catchment Area Survey. Am J Psychiatry 1995; 152:280-282.
  • 20. Tamam L. Bipolar bozukluk ile anksiyete bozuk- luğu birlikteliği: Bir gözden geçirme. Türk Psiki- yatri Dergisi 2007; 18:59-71.
  • 21. Hantouche EG, Angst J, Demonfaucon C, Perugi G, Lancrenon S, Akiskal HS. Cyclothymic OCD: a distinct form? J Affect Disord 2003; 75:1-10.
  • 22. Shimizu E, Hashimoto K, Iyo M. Ethnic difference of the BDNF 196G/A (val66met) polymorphism frequencies: the possibility to explain ethnic mental traits. Am J Med Genet B Neuropsychiatr Genet 2004; 126:122-123.
  • 23. Gratacos M, Gonzalez JR, Mercader JM, de Cid R, Urretavizcaya M, Estivill X. Brain-derived neurotrophic factor Val66Met and psychiatric disorders: meta-analysis of case-control studies confirm association to substance-related disor- ders, eating disorders, and schizophrenia. Biol Psychiatry 2007; 61:911-922.
  • 24. Strauss J, Barr CL, George CJ, Devlin B, Vetro A, Kiss E, et al. Brain-derived neurotrophic factor variants are associated with childhood-onset mood disorder: confirmation in a Hungarian sample. Mol Psychiatry 2005; 10:861-867.
  • 25. Skibinska M, Hauser J, Czerski PM, Leszc- zynska-Rodziewicz A, Kosmowska M, Kapelski P, et al. Association analysis of brain-derived neurotrophic factor (BDNF) gene Val66Met poly- morphism in schizophrenia and bipolar affective disorder. World J Biol Psychiatry 2004; 5:215- 220.
  • 26. Rybakowski JK, Borkowska A, Czerski PM, Skibinska M, Hauser J. Polymorphism of the brain-derived neurotrophic factor gene and per- formance on a cognitive prefrontal test in bipolar patients. Bipolar disord. 2003; 5:468-472.
  • 27. Zai G, Mundo E, Strauss J, Wong GW, Kennedy JL. Brain-derived neurotrophic factor (BDNF) gene not associated with antidepressant-induced mania. Bipolar Disord 2007; 9:521-525.
  • 28. Tsai SJ. Is mania caused by overactivity of central brain-derived neurotrophic factor? Med Hypotheses 2004; 62:19-22.
  • 29. Gallinat J, Schubert F, Bruhl R, Hellweg R, Klar AA, Kehrer C, et al. Met carriers of BDNF Val66Met genotype show increased N-acetyl- aspartate concentration in the anterior cingulate cortex. Neuroimage 2010; 49:767-771.
  • 30. Hashimoto K. Brain-derived neurotrophic factor as a biomarker for mood disorders: an historical overview and future directions. Psychiatry Clin Neurosci 2010; 64:341-357.
  • 31. Kim B, Kim CY, Hong JP, Kim SY, Lee C, Joo YH. Brain-derived neurotrophic factor Val/Met polymorphism and bipolar disorder. Association of the Met allele with suicidal behavior of bipolar patients. Neuropsychobiology 2008; 58:97-103.
  • 32. Vincze I, Perroud N, Buresi C, Baud P, Bellivier F, Etain B, et al. Association between brain- derived neurotrophic factor gene and a severe form of bipolar disorder, but no interaction with the serotonin transporter gene. Bipolar disord. 2008; 10:580-587.
  • 33. Zutshi A, Reddy YC, Thennarasu K, Chandras- hekhar CR. Comorbidity of anxiety disorders in patients with remitted bipolar disorder. Eur Arch Psychiatry Clin Neurosci. 2006; 256:428-436.
  • 34. Green EK, Raybould R, Macgregor S, Hyde S, Young AH, O'Donovan MC, et al. Genetic varia- tion of brain-derived neurotrophic factor (BDNF) in bipolar disorder: case-control study of over 3000 individuals from the UK. Br J Psychiatry 2006; 188:21-25.
Anadolu Psikiyatri Dergisi-Cover
  • ISSN: 1302-6631
  • Yayın Aralığı: Yılda 6 Sayı
  • Başlangıç: 2000
  • Yayıncı: -
Sayıdaki Diğer Makaleler

Ağır psikiyatrik bozukluklar, depresyon ve sigara bırakma

L.İlhan YARGIÇ, HAYRİYE BAYKAN

Sosyal ilişkilerde kişilik özellikleri etkili mi? Sosyal ağ, yalnızlık ve algılanan sosyal desteğin aracı etki olarak incelenmesi

Nihan TEZER, HALUK ARKAR

Mirtazapine bağlı periferik ödem: Olgu sunumu

Birmay ÇAM, Hüseyin KURT

Psikiyatrik belirtilerin eşlik ettiği araknoid kistler: Olgu serisi

Sıla YAZAR, Nurhan FISTIKÇI, Gülsüm CANTÜRK, Serap OFLAZ, Ali Haydar KÜÇÜKTÜFEKÇİ, Alkin YILMAZ, Demet KUŞÇU YANDIM

Kişilerarası problem çözme davranışları, yetişkinlerdeki bağlanma yönelimleri ve psikolojik belirtiler arasındaki ilişkiler

Bahar Esin ERGİN, İHSAN DAĞ

Obezite hastalarında dürtüsellik ve dürtüselliğin beden algısı ve benlik saygısı ile ilişkisi

G SARISOY, A ATMACA, G ECEMİŞ, K GÜMÜŞ, O PAZVANTOĞLU

Olumlu ve Olumsuz Yaşantı Ölçeği: Ergenler için geçerlilik ve güvenilirlik çalışması

Bülent Baki TELEF

Şizofreni hastalarının günlük yaşam aktivite düzeyi ile aile üyelerinin bakım yükü ve dışa vuran duygu durumu ilişkisi

NURDAN ÇETİN YERLİKAYA, Meral DEMİRALP, FAHRİYE OFLAZ, Aytekin ÖZŞAHİN

Kendine zarar verme davranışı olan ergenlerde psikiyatrik belirtiler, kimlik karmaşası ve benlik saygısı

DEVRİM AKDEMİR, Ayşe ZEKİ, Dilek ÜNAL YETİMOĞLU, MAHMUT ZABİT KARA, Füsun ÇETİN ÇUHADAROĞLU

Alt sosyoekonomik düzeye sahip anne-babaların çocuk istismarı ve ihmali hakkındaki bilgi düzeyleri, deneyimleri ve kullandıkları disiplin yöntemleri

Yıldız BİLGE ALLAR, MEDİNE AYŞİN TAŞAR, Betül KILINÇOĞLU, Selda ÖZMEN, Ülkü TIRAŞ