Psikiyatrik bozukluklar ve epigenetik

EMİNE EREN KOÇAK, (Hacettepe Üniversitesi, Nörolojik ve Psikiyatrik Bilimler Enstitüsü, Ankara, Türkiye)
Aygün ERTUĞRUL (Hacettepe Üniversitesi, Tıp Fakültesi, Psikiyatri Anabilim Dalı, Ankara, Türkiye)
Türk Psikiyatri Dergisi
4 1
Yıl: 2012 Cilt: 23 Sayı: 2 Sayfa Aralığı: 130 - 140 Metin Dili: Türkçe İndeks Tarihi: 29-07-2022

Psikiyatrik bozukluklar ve epigenetik

Öz:
Epigenetik, gen ifadesinde DNA’nın baz diziliminin dışındaki değişiklikleri ifade etmekte kullanılan bir terimdir. Son yıllarda epigenetik düzenlemelerin, erişkin yaşamda gen ifadesinin dinamik şekilde kontrol edilmesinde oynadığı rol açıklık kazanmıştır. Bu nedenle psikiyatrik bozukluklarda epigenetik düzenlemelerde sağlıklı kişilerden farklılıklar araştırılmaya başlanmıştır. Bu gözden geçirmenin amacı epigenetik düzenekleri tanıtmak, stres, depresyon, şizofreni ve madde bağımlılığında epigenetik düzenlemelerin rolünü tartışmaktır. Bu amaçla “pubmed” arama motoruna epigenetik, stres, depresyon, şizofreni, madde bağımlılığı anahtar kelimeleri girilerek son 10 yılda yayınlanmış araştırma yazıları ve gözden geçirmeler değerlendirilmiştir. Çalışmalar, annelik davranışlarının ve erken yaşam streslerinin, epigenetik düzeneklerle çeşitli gen ifadelerinde sonraki nesillere aktarılabilen değişikliklere yol açtığını ve bunun geri dönüşlü olduğunu göstermiştir. Stres ve depresyonda epigenetik düzenlemeleri inceleyen çalışmalar hipotalamo-pitüiter-adrenal (HPA) eksende görev alan proteinlere vurgu yaparken, şizofreniyle ilgili çalışmalarda daha çok GABAerjik sistemdeki epigenetik değişikliklere odaklanılmıştır. Madde bağımlılığıyla ilgili çalışmalar ise maddelerin kısa veya uzun süreli epigenetik değişikliklere yol açarak çok sayıda genin ifadesini değiştirebildiğini göstermiştir. Bu bulgulardan hareketle epigenetik düzenlemeleri hedef alan tedavi stratejileri belirlenmiş ve sınanmaya başlanmıştır. Bunlar içinde histon deasetilaz inhibitörleri umut vaat etmektedir. Sonuç olarak psikiyatrik bozukluklarda epigenetik düzeneklerin daha iyi anlaşılması ve yeni tedavi stratejileri geliştirilebilmesi için ek çalışmalara gereksinim vardır.
Anahtar Kelime:

Konular: Psikiyatri

Psychiatric disorders and epigenetics

Öz:
The term epigenetic refers to long-lasting changes in gene expression that are beyond the DNA base sequence. Understanding the dynamic role of epigenetic mechanisms in the regulation of gene expression in adulthood has led researchers to investigate epigenetic mechanisms in psychiatric disorders. The aim of this review was to describe epigenetic mechanisms and to discuss the role of epigenetic modifications in stress, depression, schizophrenia, and substance dependence. For this purpose PubMed was searched using the keywords epigenetic, stress, depression, schizophrenia, and substance dependence; studies published between 2000 and 2011 were reviewed. Different maternal behavioral patterns and early life stress have been reported to yield heritable changes in gene expression via epigenetic mechanisms, which are reversible. Studies that investigated the role of epigenetic modifications in stress and depression focused on the proteins involved in the regulation of the hypothalamo-pituitary adrenal (HPA) axis, whereas epigenetic studies of schizophrenia primarily focused on changes in the GABAergic system. Studies on substance dependence, on the other hand, showed that substance use might change the expression of many genes by causing short- or long-lasting epigenetic modifications. These findings have led to the development of new therapeutic strategies that target epigenetic mechanisms. Among these strategies, histone deacetylase inhibitors are especially promising. More studies are needed to improve our understanding of the role of epigenetic modifications in the development of psychiatric disorders, and to aid in the development of new treatment strategies that focus on epigenetic mechanisms.
Anahtar Kelime:

Konular: Psikiyatri
Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • Abdolmaleky HM, Cheng KH ve ark. (2006) Hypomethylation of MB-COMT promoter is a major risk factor for schizophrenia and bipolar disorder. Hum Mol Genet, 15:3132-45.
  • Abdolmaleky HM, Cheng KH, Russo A ve ark. (2005) Hypermethylation of the reelin (RELN) promoter in the brain of schizophrenic patients: a preliminary report. Am J Med Genet B Neuropsychiatr Genet, 134(1):60-6.
  • Akbarian S, Kim JJ, Potkin SG ve ark. (1995) Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics. Arch Gen Psychiatry, 52:258-66.
  • Antun FT, Burnett GB, Cooper AJ ve ark. (1971) The effects of L-methionine (without MAOI) in schizophrenia. J Psychiatr Res, 8:63-71.
  • Benes FM, Lim B, Matzilevich D ve ark. (2008) Circuitry-based gene expression profiles in GABA cells of the trisynaptic pathway in schizophrenics versus bipolars. Proc Natl Acad Sci U S A, 105:20935-20940.
  • Benes FM, Lim B, Matzilevich D ve ark. (2007) Regulation of the GABA cell phenotype in hippocampus of schizophrenics and bipolars. Proc Natl Acad Sci U S A, 104:10164-10169.
  • Bibb JA, Chen J, Taylor JR ve ark. (2001) Effects of chronic exposure to cocaine are regulated by the neuronal protein Cdk5. Nature, 410:376-80.
  • Brami-Cherrier K, Valjent E, Herve D ve ark. (2005) Parsing molecular and behavioral effects of cocaine in mitogen- and stress-activated protein kinase- 1-deficient mice. J Neurosci, 25:11444-54.
  • Cald ji C, Tannenbaum B, Sharma S ve ark. (1998) Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat. Proc Natl Acad Sci U S A, 95:5335-40.
  • Casp i A, Sugden K, Moffitt TE ve ark. (2003) Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene. Science, 301:386-9.
  • Cham pagne F, Diorio J, Sharma S ve ark. (2001) Naturally occurring variations in maternal behavior in the rat are associated with differences in estrogeninducible central oxytocin receptors. Proc Natl Acad Sci U S A, 98:12736- 741.
  • Cham pagne FA, Meaney MJ (2006) Stress during gestation alters postpartum maternal care and the development of the offspring in a rodent model. Biol Psychiatry, 59:1227-35.
  • Cham pagne FA, Weaver IC, Diorio J ve ark. (2006) Maternal care associated with methylation of the estrogen receptor-alpha1b promoter and estrogen receptor-alpha expression in the medial preoptic area of female offspring. Endocrinology, 147:2909-15.
  • Cohe n SM, Nichols A, Wyatt R ve ark. (1974) The administration of methionine to chronic schizophrenic patients: a review of ten studies. Biol Psychiatry, 8:209-25.
  • Cost a E, Chen Y, Dong E ve ark. (2009) GABAergic promoter hypermethylation as a model to study the neurochemistry of schizophrenia vulnerability. Expert Rev Neurother, 9:87-98.
  • Cost a E, Davis JM, Dong E ve ark. (2004) A GABAergic cortical deficit dominates schizophrenia pathophysiology. Crit Rev Neurobiol, 16:1-23.
  • Covi ngton HE 3rd, Maze I, LaPlant QC ve ark. (2009) Antidepressant actions of histone deacetylase inhibitors. J Neurosci, 29:11451-60.
  • de K loet ER, Joels M, Holsboer F (2005) Stress and the brain: From adaptation to disease. Nat Rev Neurosci, 6:463-75.
  • Delc uve GP, Rastegar M, Davie JR (2009) Epigenetic control. J Cell Physiol, 219:243-50.
  • Demp ster EL, Mill J, Craig IW ve ark. (2006) The quantification of COMT mRNA in post mortem cerebellum tissue: Diagnosis, genotype, methylation and expression. BMC Med Genet, 7:10.
  • Deti ch N, Bovenzi V, Szyf M (2003) Valproate induces replication-independent active DNA demethylation. J Biol Chem, 278:27586-92.
  • Dong E, Agis-Balboa RC, Simonini MV ve ark. (2005) Reelin and glutamic acid decarboxylase67 promoter remodeling in an epigenetic methionine-induced mouse model of schizophrenia. Proc Natl Acad Sci U S A, 102:12578-83.
  • Dong E, Nelson M, Grayson DR ve ark. (2008) Clozapine and sulpiride but not haloperidol or olanzapine activate brain DNA demethylation. Proc Natl Acad Sci U S A, 105:13614-19.
  • Drum mond DC (2000) What does cue-reactivity have to offer clinical research? Addiction, 95 (Suppl. 2): 129-44.
  • Duma n RS, Monteggia LM (2006) A neurotrophic model for stress-related mood disorders. Biol Psychiatry, 59:1116-27.
  • Fahr bach SE, Morrell JI, Pfaff DW (1985) Possible role for endogenous oxytocin in estrogen-facilitated maternal behavior in rats. Neuroendocrinology, 40:526-32.
  • Fate mi SH, Earle JA, McMenomy T (2000) Reduction in Reelin immunoreactivity in hippocampus of subjects with schizophrenia, bipolar disorder and major depression. Mol Psychiatry, 5:654-63, 571.
  • Fels enfeld G, Groudine M (2003) Controlling the double helix. Nature, 421:448-53.
  • Fran cis D, Diorio J, Liu D ve ark. (1999) Nongenomic transmission across generations of maternal behavior and stress responses in the rat. Science, 286:1155-8.
  • Freeman WM, Patel KM, Brucklacher RM ve ark. (2008) Persistent alterations in mesolimbic gene expression with abstinence from c ocaine selfadministration. Neuropsychopharmacology, 33:1807-17.
  • Fuma galli F, Molteni R, Racagni G ve ark. (2007) Stress during development: Impact on neuroplasticity and relevance to psychopathology. Prog Neurobiol, 81:197-217.
  • Gavi n DP, Sharma RP (2010) Histone modifications, DNA methylation, and schizophrenia. Neurosci Biobehav Rev, 34:882-8.
  • Glov er V (1997) Maternal stress or anxiety in pregnancy and emotional development of the child. Br J Psychiatry, 171:105-6.
  • Gluc kman PD, Hanson MA, Cooper C ve ark. (2008) Effect of in utero and early-life conditions on adult health and disease. N Engl J Med, 359:61-73.
  • Gold PW, Chrousos GP (2002) Organization of the stress system and its dysregulation in melancholic and atypical depression: High vs low CRH/ NE states. Mol Psychiatry, 7:254-75.
  • Gray son DR, Jia X, Chen Y ve ark. (2005) Reelin promoter hypermethylation in schizophrenia. Proc Natl Acad Sci U S A, 102:9341-6.
  • Gree n J, Goldwyn R (2002) Annotation: Attachment disorganisation and psychopathology: New findings in attachment research and their potential implications for developmental psychopathology in childhood. J Child Psychol Psychiatry, 43: 835-46.
  • Grim m JW, Lu L, Hayashi T ve ark. (2003) Time-dependent increases in brainderived neurotrophic factor protein levels within the mesolimbic dopamine system after withdrawal from cocaine: Implications for incubation of cocaine craving. J Neurosci, 23:742-7.
  • Guid otti A, Auta J, Davis JM ve ark. (2000) Decrease in reelin and glutamic acid decarboxylase67 (GAD67) expression in schizophrenia and bipolar disorder: a postmortem brain study. Arch Gen Psychiatry, 57:1061-9.
  • Hash imoto T, Arion D, Unger T ve ark. (2008) Alterations in GABA-related transcriptome in the dorsolateral prefrontal cortex of subjects with schizophrenia. Mol Psychiatry, 13:147-61.
  • Huan g HS, Akbarian S (2007) GAD1 mRNA expression and DNA methylation in prefrontal cortex of subjects with schizophrenia. PLoS One, 2:e809.
  • Huang HS, Matevossian A, Whittle C ve ark. (2007) Prefrontal dysfunction in schizophrenia involves mixed-lineage leukemia 1-regulated histone methylation at GABAergic gene promoters. J Neurosci, 27:11254-62. Impa gnatiello F, Guidotti AR, Pesold C ve ark. (1998) A decrease of reelin expression as a putative vulnerability factor in schizophrenia. Proc Natl Acad Sci U S A, 95:15718-23.
  • Iwam oto K, Kato T (2009) Epigenetic profiling in schizophrenia and major mental disorders. Neuropsychobiology, 60:5-11.
  • Jaen isch R, Bird A (2003) Epigenetic regulation of gene expression: How the genome integrates intrinsic and environmental signals. Nat Genet, 33 (Suppl): 245-54.
  • Kald a A, Heidmets LT, Shen HY ve ark. (2007) Histone deacetylase inhibitors modulates the induction and expression of amphetamine-induced behavioral sensitization partially through an associated learning of the environment in mice. Behav Brain Res, 181:76-84.
  • Kami nsky ZA, Tang T, Wang SC ve ark. (2009) DNA methylation profiles in monozygotic and dizygotic twins. Nat Genet, 41:240-5.
  • Kend ler KS, Karkowski LM, Prescott CA (1999) Causal relationship between stressful life events and the onset of major depression. Am J Psychiatry, 156:837-41.
  • Kirk patrick B, Buchanan RW, Ross DE ve ark. (2001) A separate disease within the syndrome of schizophrenia. Arch Gen Psychiatry, 58:165-71.
  • Korn berg RD (1974) Chromatin structure: a repeating unit of histones and DNA. Science, 184:868-71.
  • Kouz arides T (2007) Chromatin modifications and their function. Cell, 128:693-705.
  • Kuma r A, Choi KH, Renthal W ve ark. (2005) Chromatin remodeling is a key mechanism underlying cocaine-induced plasticity in striatum. Neuron, 48:303-14.
  • Kund akovic M, Chen Y, Costa E ve ark. (2007) DNA methyltransferase inhibitors coordinately induce expression of the human reelin and glutamic acid decarboxylase 67 genes. Mol Pharmacol, 71:644-53.
  • Kund akovic M, Chen Y, Guidotti A ve ark. (2009) The reelin and GAD67 promoters are activated by epigenetic drugs that facilitate the disruption of local repressor complexes. Mol Pharmacol, 75:342-54.
  • Lach ner M, Jenuwein T (2002) The many faces of histone lysine methylation. Curr Opin Cell Biol, 14:286-98.
  • Lee MG, Wynder C, Schmidt DM ve ark. (2006) Histone H3 lysine 4 demethylation is a target of nonselective antidepressive medications. Chem Biol, 13:563-7.
  • Levi ne AA, Guan Z, Barco A ve ark. (2005) CREB-binding protein controls response to cocaine by acetylating histones at the fosB promoter in the mouse striatum. Proc Natl Acad Sci U S A, 102:19186-91.
  • Lewi s DA, Hashimoto T, Volk DW (2005) Cortical inhibitory neurons and schizophrenia. Nat Rev Neurosci, 6:312-24.
  • Liu D, Diorio J, Tannenbaum B ve ark. (1997) Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress. Science, 277:1659-62.
  • Lupi en SJ, McEwen BS, Gunnar MR ve ark. (2009) Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat Rev Neurosci, 10:434-5.
  • Maze I, Covington HE 3rd, Dietz DM ve ark. (2010) Essential role of the histone methyltransferase G9a in cocaine-induced plasticity. Science, 327:213-6.
  • Maze I, Feng J, Wilkinson MB ve ark. (2011) Cocaine dynamically regulates heterochromatin and repetitive element unsilencing in nucleus accumbens. Proc Natl Acad Sci U S A, 108:3035-40.
  • McCl ung CA, Nestler EJ (2003) Regulation of gene expression and cocaine reward by CREB and DeltaFosB. Nat Neurosci, 6:1208-15.
  • McGo wan PO, Sasaki A, D’Alessio AC ve ark. (2009) Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci, 12:342-8.
  • Meti vier R, Gallais R, Tiffoche C ve ark. (2008) Cyclical DNA methylation of a transcriptionally active promoter. Nature, 452:45-50.
  • Mill J, Tang T, Kaminsky Z ve ark. (2008) Epigenomic profiling reveals DNAmethylation changes associated with major psychosis. Am J Hum Genet, 82:696-711.
  • Muel ler BR, Bale TL (2008) Sex-specific programming of offspring emotionality after stress early in pregnancy. J Neurosci, 28:9055-65.
  • Murg atroyd C, Patchev AV, Wu Y ve ark. (2009) Dynamic DNA methylation programs persistent adverse effects of early-life stress. Nat Neurosci, 12:1559-66.
  • Murp hy BC, O’Reilly RL, Singh SM (2005) Site-specific cytosine methylation in S-COMT promoter in 31 brain regions with implications for studies involving schizophrenia. Am J Med Genet B Neuropsychiatr Genet, 133(1):37-42.
  • Nest ler EJ, Barrot M, DiLeone RJ ve ark. (2002) Neurobiology of depression. Neuron, 34:13-25.
  • Noh JS, Sharma RP, Veldic M ve ark. (2005) DNA methyltransferase 1 regulates reelin mRNA expression in mouse primary cortical cultures. Proc Natl Acad Sci U S A, 102:1749-54.
  • Numa n M, Sheehan TP (1997) Neuroanatomical circuitry for mammalian maternal behavior. Ann N Y Acad Sci, 807:101-25.
  • Rent hal W, Kumar A, Xiao G ve ark. (2009) Genome-wide analysis of chromatin regulation by cocaine reveals a role for sirtuins. Neuron, 62:335-48.
  • Rent hal W, Maze I, Krishnan V ve ark. (2007) Histone deacetylase 5 epigenetically controls behavioral adaptations to chronic emotional stimuli. Neuron, 56:517-29.
  • Rent hal W, Nestler EJ (2008) Epigenetic mechanisms in drug addiction. Trends Mol Med, 14:341-50.
  • Rent hal W, Nestler EJ (2009) Chromatin regulation in drug addiction and depression. Dialogues Clin Neurosci, 11:257-68.
  • Rich ards EJ (2006) Inherited epigenetic variation--revisiting soft inheritance. Nat Rev Genet, 7:395-401.
  • Roth TL, Lubin FD, Funk AJ ve ark. (2009) Lasting epigenetic influence of early-life adversity on the BDNF gene. Biol Psychiatry, 65:760-9.
  • Ruzi cka WB, Zhubi A, Veldic M ve ark. (2007) Selective epigenetic alteration of layer I GABAergic neurons isolated from prefrontal cortex of schizophrenia patients using laser-assisted microdissection. Mol Psychiatry, 12:385-97.
  • Schr oeder FA, Lin CL, Crusio WE ve ark. (2007) Antidepressant-like effects of the histone deacetylase inhibitor, sodium butyrate, in the mouse. Biol Psychiatry, 62:55-64.
  • Schr oeder FA, Penta KL, Matevossian A ve ark. (2008) Drug-induced activation of dopamine D(1) receptor signaling and inhibition of class I/II histone deacetylase induce chromatin remodeling in reward circuitry and modulate cocaine-related behaviors. Neuropsychopharmacology, 33:2981-92.
  • Shar ma RP, Grayson DR, Gavin DP (2008) Histone deactylase 1 expression is increased in the prefrontal cortex of schizophrenia subjects: Analysis of the National Brain Databank microarray collection. Schizophr Res, 98:111-7.
  • Sieg mund KD, Connor CM, Campan M ve ark. (2007) DNA methylation in the human cerebral cortex is dynamically regulated throughout the life span and involves differentiated neurons. PLoS One, 2:e895.
  • Swea tt JD (2009) Experience-dependent epigenetic modifications in the central nervous system. Biol Psychiatry, 65:191-7.
  • Tamu ra Y, Kunugi H, Ohashi J ve ark. (2007) Epigenetic aberration of the human REELIN gene in psychiatric disorders. Mol Psychiatry, 12:519, 593-600.
  • Toch igi M, Iwamoto K, Bundo M ve ark. (2008) Methylation status of the reelin promoter region in the brain of schizophrenic patients. Biol Psychiatry, 63:530-3.
  • Torr ey EF, Barci BM, Webster MJ ve ark. (2005) Neurochemical markers for schizophrenia, bipolar disorder, and major depression in postmortem brains. Biol Psychiatry, 57:252-60.
  • Trem olizzo L, Carboni G, Ruzicka WB ve ark. (2002) An epigenetic mouse model for molecular and behavioral neuropathologies related to schizophrenia vulnerability. Proc Natl Acad Sci U S A, 99:17095-100.
  • Trem olizzo L, Doueiri MS, Dong E ve ark. (2005) Valproate corrects the schizophrenia-like epigenetic behavioral modifications induced by methionine in mice. Biol Psychiatry, 57:500-9.
  • Tsan kova N, Renthal W, Kumar A ve ark. (2007) Epigenetic regulation in psychiatric disorders. Nat Rev Neurosci, 8:355-67.
  • Tsan kova NM, Berton O, Renthal W ve ark. (2006) Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nat Neurosci, 9:519-25.
  • Tsan kova NM, Kumar A, Nestler EJ (2004) Histone modifications at gene promoter regions in rat hippocampus after acute and chronic electroconvulsive seizures. J Neurosci, 24:5603-10.
  • Veld ic M, Caruncho HJ, Liu WS ve ark. (2004) DNA-methyltransferase 1 mRNA is selectively overexpressed in telencephalic GABAergic interneurons of schizophrenia brains. Proc Natl Acad Sci U S A, 101:348-53.
  • Veld ic M, Guidotti A, Maloku E ve ark. (2005) In psychosis, cortical interneurons overexpress DNA-methyltransferase 1. Proc Natl Acad Sci U S A, 102:2152- 7.
  • Weav er IC, Cervoni N, Champagne FA ve ark. (2004) Epigenetic programming by maternal behavior. Nat Neurosci, 7:847-54.
  • Weav er IC, Champagne FA, Brown SE ve ark. (2005) Reversal of maternal programming of stress responses in adult offspring through methyl supplementation: Altering epigenetic marking later in life. J Neurosci, 25:11045-54.
  • Yıld ırım E, Zhang Z, Uz T ve ark. (2003) Valproate administration to mice increases histone acetylation and 5-lipoxygenase content in the hippocampus. Neurosci Lett, 345:141-3.
  • Zhub i A, Veldic M, Puri NV ve ark. (2009) An upregulation of DNAmethyltransferase 1 and 3a expressed in telencephalic GABAergic neurons of schizophrenia patients is also detected in peripheral blood lymphocytes. Schizophr Res, 111:115-22.
APA EREN KOÇAK E, ERTUGRUL A (2012). Psikiyatrik bozukluklar ve epigenetik. , 130 - 140.
Chicago EREN KOÇAK EMINE,ERTUGRUL Aygün Psikiyatrik bozukluklar ve epigenetik. (2012): 130 - 140.
MLA EREN KOÇAK EMINE,ERTUGRUL Aygün Psikiyatrik bozukluklar ve epigenetik. , 2012, ss.130 - 140.
AMA EREN KOÇAK E,ERTUGRUL A Psikiyatrik bozukluklar ve epigenetik. . 2012; 130 - 140.
Vancouver EREN KOÇAK E,ERTUGRUL A Psikiyatrik bozukluklar ve epigenetik. . 2012; 130 - 140.
IEEE EREN KOÇAK E,ERTUGRUL A "Psikiyatrik bozukluklar ve epigenetik." , ss.130 - 140, 2012.
ISNAD EREN KOÇAK, EMINE - ERTUGRUL, Aygün. "Psikiyatrik bozukluklar ve epigenetik". (2012), 130-140.
APA EREN KOÇAK E, ERTUGRUL A (2012). Psikiyatrik bozukluklar ve epigenetik. Türk Psikiyatri Dergisi, 23(2), 130 - 140.
Chicago EREN KOÇAK EMINE,ERTUGRUL Aygün Psikiyatrik bozukluklar ve epigenetik. Türk Psikiyatri Dergisi 23, no.2 (2012): 130 - 140.
MLA EREN KOÇAK EMINE,ERTUGRUL Aygün Psikiyatrik bozukluklar ve epigenetik. Türk Psikiyatri Dergisi, vol.23, no.2, 2012, ss.130 - 140.
AMA EREN KOÇAK E,ERTUGRUL A Psikiyatrik bozukluklar ve epigenetik. Türk Psikiyatri Dergisi. 2012; 23(2): 130 - 140.
Vancouver EREN KOÇAK E,ERTUGRUL A Psikiyatrik bozukluklar ve epigenetik. Türk Psikiyatri Dergisi. 2012; 23(2): 130 - 140.
IEEE EREN KOÇAK E,ERTUGRUL A "Psikiyatrik bozukluklar ve epigenetik." Türk Psikiyatri Dergisi, 23, ss.130 - 140, 2012.
ISNAD EREN KOÇAK, EMINE - ERTUGRUL, Aygün. "Psikiyatrik bozukluklar ve epigenetik". Türk Psikiyatri Dergisi 23/2 (2012), 130-140.
Sayfa Oluşturulma Tarihi
22-04-2024 18:5

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