Elbozan Birgül CUMURCU, Rifat KARLIDAĞ, Kaya SARAÇ, SÜHEYLA ÜNAL, Cemal ÖZCAN

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Bipolar affektif bozukluklu hastalarda lityum ve olanzapin tedavisinin etkileri: Beyin MRSs bulguları

Amaç: Bu çalışmada, remisyon dönemindeki bipolar affektif bozukluklu hastalarda lityum ve olanzapin tedavisi ile beyin manyetik rezonans spektroskopi (MR spektroskopi) bulgularındaki değişiklikler ve bunun nöroprotektivite ile ilişkisi araştırıldı. Yöntem: Psikiyatri polikliniğinde izlenen, 3 yıl boyunca manik ve depresif bir atak geçirmemiş ve son 6 aydır sadece lityum tedavisi almakta olan 10 bipolar affektif bozukluk hastası çalışmaya alındı. Hastalar lityum kullandıkları dönemde, lityumun kesilmesini takiben 14. günde ve olanzapin başlandıktan sonraki 4. haftanın sonunda olmak üzere 3 kez değerlendirildi. Her bir değerlendirme klinik psikiyatrik görüşme, Hamilton depresyon derecelendirme Ölçeği (HDÛÖ) ve Bech-Rafaelson Mani Ölçeği (BRMÖ) uygulaması ve MR spektroskopi çekimini kapsadı. MR spektroskopide, sağ prefrontal korteks ve sol hipokampüs bölgelerinde kantitatif olarak N-asetil aspartat (NAA), kolin (Cho) pikleri ölçüldü ve bunların kreatine (Cr) pikine oranlarına bakıldı. Her 3 çekimdeki değerler birbiriyle karşılaştırıldı. Bulgular: Çalışmaya 5 kadın ve 5 erkek hasta katıldı. Ortalama yaşları 33.10+9.17yıl idi. Lityum alırken, ilaçsız dönemde ve.olanzapin alırken çekilen MR spektroskopilerinde NAA/Cr ve Cho/Cr oranları arasında istatistiksel açıdan anlamlı farklılık saptanmadı. Sonuç: Remisyonda bipolar affektif bozukluklu hastalarda lityum ve olanzapin tedavisiyle beyin NAA ve Cho düzeylerinin değişmediğini düşündürmektedir.
Anahtar Kelimeler:

Lityum, İki uçlu duygu durum bozukluğu, Kolin, Magnetik rezonans spektroskopi, Antipsikotik ajanlar, Aspartik asit, Duygudurum bozuklukları

Evaluation of neuroprotective effect of lithium and olanzapine on brain tissue in bipolar affective disorder: A comperative study with MR spectroscopy

Objective: In this study we searched the caused by lithium and olanzapine treatment in brain magnetic resonance spetroscopy (MR spectroscopy) and its reladuring remission. Methods: Ten patients with bipolar affective disorders who were followed-up in psychiatry outpatient clinic between February and June 2003, had no manic or depressive attacs for the last 3 years and had lithium as the only therapy for the last 6 months were included in this study. They were evaluated during and 14 days after cessation of lithium treatment and at the end of 4th week on olazapine treatment. Clinical interview, Hamilton Depression Rating Scale (HAM-b) psychometric evaluation test, Brief Psychiatric Rating Scale (BPRS) and magnetic resonance spectroscopy (MR spectroscopy) were assesed on each evaluation. According to the results of interview and psychometric evaluation, patients who were diagnosed as manic or depressive disorder were ruled out of the study. Cases underwent single voxel MR spect with PRESS sequence. The peak of N-acetyl aspartate (NAA), Choline (Cho) and their ratio to Creatinine (Cr) peak were evaluated quantitavely right prefrontal cortex and left hippocampus areas on MR spectroscopy. Results of three MR spects were compared. Results: Five women and 5 men comleted to the study, mean age of the patients were 33.10±9.17. No significant difference was determined between NAA/Cr and Cho/Cr values of MR spects, in each three phases as on lithium treatment, in unmedicated period and in olanzapine treatment. Conclusion: We did not find any significant effect of these drugs on brain NAA and Cho levels in the remission phases of bipolar affective disorder. tionship with neuroprotectivity in patients with bipolar affective disorder
Keywords:

Lithium, Bipolar Disorder, Choline, Magnetic Resonance Spectroscopy, Antipsychotic Agents, Aspartic Acid, Mood Disorders,

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  • 1. Keck Jr PE, McElroy SL. Redefining mood stabilization. J Affec Disord 2003; 73:163-169.
  • 2. Adams JM, Cory S. The Bcl-2-protein family: arbiters of cell survival. Science 1998; 281:1322-1326.
  • 3. Manji HK, Moore GJ, Chen G. Lithium at 50: have the neuroprotective effects of this unique cation been overlooked? Biol Psychiatry 1999; 46:929-940.
  • 4. Manji HK, Potter WZ, Lenox RH. Signal transduction pathways: molecular targets for lithium’s action. Arch Gen Psychiatry 1995; 52:531-543.
  • 5. Bruckheimer EM, Cho SH, Sarkiss M, Hermann J, McDonnell TJ. The Bcl-2 gene family and apoptosis. Adv Biochem Eng Biotechnal 1998; 62:75-105.
  • 6. Jope RS. Anti-bipolar therapy: mechanism of action of lithium. Mol Psychiatry 1999; 4:117-128.
  • 7. Rajkowska G, Miguel-Hidalgo JJ, Wei J, Dilley G, Pittman SD, Meltzer HY ve ark. Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biol Psychiatry 1999; 45:1085-1098.
  • 8. Thonen H, Barde YA. Physiology of the nevre growth factor. Physiol Rev 1980; 60:1284-1335.
  • 9. Levi-Montalcini R. The nevre growth factor 35 years later. Science 1987; 237:1154-1162.
  • 10. Greene LA, Kaplan DR. Early events in neurotrophin signalling via TRK and p75 reseptors. Curr Opin Neurobiol 1995; 5:579-587.
  • 11. Selemon LD, Rajkowska G, Goldman-Rakic PS. Abnormally high neuronal density in the schizophrenic cortex. Arch Gen Psychiatry 1995; 52:805-881.
  • 12. Poscual T, Gonzalez JL. A protective effect of lithium on rat behavior altered by ibotenic acid lesion of the basal forebrain cholinergic system. Brain Res 1995; 695:289-292.
  • 13. Jeste DV, Lohr JB. Hippocampal pathologic findings in schizophrenia. A morphometric study. Arch Gen Psychiatry 1989; 46:1019-1024.
  • 14. Frukawa K, Estus S, Fu W, Mark RJ, Mattson MP. Neuroprotective action of cycloheximide involves induction of bcl-2 and antioxidant pathways. J Cell Biol 1997; 136:1137-1149.
  • 15. Kato T, Hamakawa H, Shioiri T, Murashita J, Takahashi Y, Takaha S ve ark. Choline-containing compounds detected by proton magnetic resonance spectroscopy in basal ganglia in bipolar disorder. J Psychiatry Neurosci 1996; 21:248-254.
  • 16. Kaplan DR, Miller FD. Signal transduction by the neurotrophin reseptors. Curr Opin Cell Biol 1997; 9:213-221.
  • 17. Hamakawa H, Kato T, Murashita J, Kato N. Quantitative proton magnetic resonance spectroscopy of the basal ganglia in patients with affective disorders. Eur Arch Psychiatry Clin Neurosci 1998; 248:53-58.
  • 18. Hamakawa H, Kato T, Shioiri T, Inubushi T, Kato N. Quantitative proton magnetic resonance spectroscopy of the bilateral frontal lobes with bipolar disorder. Psychol Med 1999; 29:639-644.
  • 19. Stoll AL, Renshaw PF, Sachs GS, Guimaraes AR, Miller C, Cohen B, et al: The human brain resonance of choline-containing compound similar in patients receiving lithium treatment and controls: In vivo proton magnetic resonance spectroscopy study. Biol Psychiatry 1992; 32:944-949.
  • 20. Moore CM, Breeze JL, Gruber SA, Babb SM, Frederick BB, Villafue RA ve rak. Choline, myoinositol and mood in bipolar disorder: a proton magnetic resonance spectroscopic imaging study of the anterior cingulate cortex. Bipolar Disord 2000; 2:207-216.
  • 21. Lovestone S, Davis DR, Webster MT, Kaech S, Brion JP, Matus A ve ark. Lithium reduces tau phosphorylation: Effects in living cells and in neurons at therapeutic concentrations. Biol Psychiatry 1999; 45:995-1003.
  • 22. Altınok D, Yıldız YT, Akalın A. Kitle etkisi ile seyreden bir nöro-Behçet olgusu. Tanısal ve Girişimsel Radyoloji 2000; 6:134-136.
  • 23. Oğul E. Beyin tümörleri. E Oğul (ed): Klinik Nöroloji’- de. Bursa, Nobel ve Güneş Tıp Kitapevleri, 2002, s.233-318.
  • 24. Wiederman D, Schuff N, Matson GB, Soher BJ, Du AT, Maudsley A ve ark. Short echo time multislice proton magnetic resonance spectroscopic imaging in human brain: metabolit distributions and reliability. Magn Reson Med 2001; 19:1073-1080.
  • 25. Danielsen ER, Ross B. Magnetik Resonance Spectroscopy Diagnosis of Neurological Diseases. Pasadena, California, Marcel Dekker, 1995.
  • 26. D’Mello SR, Anelli R, Calissano P. Lithium induces apoptosis in immature cerebellar granule cells but promotes survival of mature neurons. Exp Cell Res 1994; 211:332-338.
  • 27. Chen DF, Schneider GE, Martinou JC, Tonegawa S. Bcl-2 promotes regeneration of severed axons in mammalian CNS. Nature 1997; 385:434-439.
  • 28. Wengenack TM, Curan GL, Paduslo JF. Postischemic, systematic administration of polyamine-modified superoxide dismutase reduces hippocampal CAI neurodegeneration in rat global ischemia. Brain Res 1997; 754:46-54.
  • 29. Li XM, Chlan-Fourney J, JuorioAV, Bernett VL, Shrikhande S, Keegan DL ve ark. Differential effects of olanzapine on the gene expression of superoxide dismutase and the low affinity nevre growth factor receptor. J Neurosci Res 1999; 56:72-75.
  • 30. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders. Dördüncü baskı, Washington DC, American Psychiatric Association, 2000.
  • 31. Kantarcı E, Erkoç Ş, Kulu D, Durmaz G, Arkonaç O. Bech-Rafaelson mani ölçeğinin güvenirliği. 29. Ulusal Psikiyatri Kongresi Tam Metin Kitabı, Bursa, 1993, s.87,
  • 32. Akdemir A, Örsel S, Dağ İ, İşcar N, Özbay H. Hamilton depresyon derecelendirme ölçeği (HDDÖ)’nin geçerliliği, güvenirliği ve klinikte kullanımı. 3P Dergisi 1996; 4:251-259.
  • 33. Volante C, Rukenstein A. Lithium promotes shortterm survival of PC12 cells after serum and NGF deprivation. Lithium 1993; 4:211-219.
  • 34. Nonaka S, Houng CJ, Chuang DM. Chronic lithium treatment robustly protects neurons in the central nervous system against excitotoxicity by inhibiting N-methly-D-aspartate receptor-mediated calcium influx. Proceedings of the National Academy of Sciences 1998; 95:2642-2647.
  • 35. Alvarez G, Munoz-Montano JR, Satrustegui J, Avila J, Bogonez E, Diaz-Nido J. Lithium protects cultured neurodegeneration. FEBS Lett 1999; 453:260-264.
  • 36. Chuang DM, Chen RW, Chalecka-Franaszek E, Ren M, Haşhimato R, Senatorou V ve ark. Neuroprotective models of discases. Bipolar Disord 2002; 4:129-136.
  • 37. Hashimato R, Takei N, Shimazu K, Christ L, Lu B, Chuang DM. Lithium induces brain-neurotrophic factor and activates Trk B in rodent cortical neurons: an essential step otection against glutamate excitotoxicity. Neuropharmacology 2002; 43:1173-1179.
  • 38. Moore GJ, Bebchuk JM, Hasanat K, Chen G, Seraji-Bozorgzad N, Wilds IB ve ark. Lithium increases nasetyl-aspartate in the human brain: in vivo evidence in support of bcl-2’s neurotrophic effects? Biol Psychiatry 2000; 48:1-8.
  • 39. Chen RW, Chuang DM. Long term lithium treatment supresses p53 and Bax expression but increases Bcl-2 expression. A prominent role in neuroprotection against excitotoxicity. J Biol Chem 1999; 274: 6039-6042.
  • 40. Manji HK, Moore Gregory J, Chen G. Clinical and preclinical evidence for the neurotrophic effect of mood stabilizers. Implications for the pathophysiology and treatment of manic-depressive illness. Soc Biol Psychiatry 2000; 48:740-754.
  • 41. Drevets WC. Neuroimaging studies of mood disorders. Biol Psychiatry 2000; 48:813-828.
  • 42. Lindquist DM, Hawk RM, Karson CN, Komoroski RA. Effects of antipsychotic drugs on metabolite rations in rat brain in vivo. Magn Reson Med 2000; 43:355-358.
Anadolu Psikiyatri Dergisi-Cover
  • ISSN: 1302-6631
  • Yayın Aralığı: Yılda 6 Sayı
  • Başlangıç: 2000
  • Yayıncı: -
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