Majör Depresif Bozuklukta Gen-Çevre Etkileşimi

Year 2024, Volume: 6 Issue: 2, 240 - 265, 30.06.2024

Beyza Şanal Güngör , Ali Güngör

https://doi.org/10.47793/hp.1350943

Abstract

Majör depresif bozukluk (MDB), ruhsal bozukluklar içerisinde tüm dünyada görülmekte olan yaygın, bireyi zaman içerisinde güçten düşüren bir duygudurum bozukluğudur. MDB etiyolojisinde genetik ve çevresel faktörler birlikte rol oynamaktadır. Bu çalışmanın amacı dünyada en önemli ruhsal bozukluklar arasında yer alan majör depresif bozukluğu gen-çevre etkileşimi açısından incelemektir. Araştırma kapsamında DergiPark, Google Akademik, PsycARTICLES, PubMed, TR Dizin ve Web of Science veri tabanlarında “majör depresif bozukluk”, “depresyon”, “epigenetik”, “depresyon ve epigenetik”, “depresyon ve genetik”, “depresyon ve çevre” anahtar sözcük kullanımı ile İngilizce ve Türkçe tam metin olarak ulaşılan makaleler gözden geçirilmiştir. Alanyazında yer alan gen-çevre etkileşim çalışmaları üzerinde durularak epigenetik mekanizmalar incelenmiştir. Genetik faktörlerin çevresel faktörlerle etkileşimi sonucunda meydana gelen klinik tablo çalışma kapsamında alanyazın ışığında tartışılmıştır. Buna göre, bozukluğun oluşumuna neden olan belirli tek bir genetik faktörden bahsedilememektedir. Olumsuz çevre yaşantılarının genetik ifade üzerinde güçlü etkileri bulunmakla birlikte, bireysel farklılıklar durumu önemli ölçüde değiştirebilmektedir. Bütüncül bir gen-çevre etkileşim modeli, genetik polimorfizmler ve DNA metilasyonu gibi epigenetik mekanizmalar ve çevresel etkiler arasındaki etkileşim mekanizmalarını içermelidir. Yapılan çalışmada majör depresif bozukluk ve gen-çevre etkileşimine genel bakış açısı sunmanın hastalığın doğasını doğru kavramada yardımcı olarak bireylerin yaşam kalitelerinin artmasına, hastalık yükünün azalması neticesinde maliyette ciddi tasarruflara ve morbidite ile mortaliteyi azaltmasına katkı sağlayacağı düşünülmektedir.

Keywords

majör depresif bozukluk, epigenetik, gen-çevre etkileşimi, depresyon

Thanks

Değerli Editör, “Majör Depresif Bozuklukta Gen-Çevre Etkileşimi” adlı çalışmamızı derginizde değerlendirilmesi amacıyla göndermekteyiz. Bu çalışma herhangi bir dergiye değerlendirilmesi ve/veya yayınlanması için gönderilmemiştir. Çalışma için herhangi bir kurumdan destek alınmamış olup yazarlarla çıkar çatışması da bulunmamaktadır. Sizden olumlu geri bildirim alma umuduyla, çalışmalarınızda başarılar ve kolaylıklar dilerim. Saygılarımla, Uzman Psikolojik Danışman & Klinik Psikolog Beyza ŞANAL GÜNGÖR Hacettepe Üniversitesi, Beytepe, Ankara, Turkey GSM: [phone] e-mail: [e-mail]

Gene-Environment Interaction in Major Depressive Disorder

Abstract

Major depressive disorder (MDD) is a prevalent mood disorder worldwide, characterized by a pervasive feeling of low mood that diminishes one's capacity over time. The etiology of MDD involves the interplay of genetic and environmental factors. This study aims to scrutinize MDD through the lens of gene-environment interaction, considering it as one of the most significant mental disorders globally. In this research, articles sourced in English and Turkish, employing keywords such as "major depressive disorder", "depression", "epigenetics", "depression and epigenetics", "depression and genetics", and "depression and environment" from databases including DergiPark, Google Scholar, PsycARTICLES, PubMed, TR Index, and Web of Science were reviewed as full text. Epigenetic mechanisms were examined with an emphasis on gene-environment interaction studies in the existing literature. The clinical manifestation arising from the interplay between genetic and environmental factors was deliberated within the study's framework. Accordingly, it is noted that a specific single genetic factor causing the disorder cannot be identified. While adverse environmental experiences have significant effects on genetic expression, individual differences can substantially modify the situation. A comprehensive gene-environment interaction model should encompass mechanisms of interaction between genetic polymorphisms, DNA methylation, and environmental influences such as stressors. It is anticipated that furnishing a comprehensive overview of MSD and gene-environment interaction in this study will enrich comprehension of the disease's nature, thereby enhancing individuals' quality of life, yielding notable cost alleviations through diminished disease burden, and curbing morbidity and mortality.

Keywords

major depressive disorder, epigenetics, gene-environment interaction, depression

References

• Agid, O., Shapira, B., Zislin, J., Ritsner, M., Hanin, B. & Murad, H., (1999). Environment and vulnerability to major psychiatric illness: a case control study of early parental loss in major depression, bipolar disorder and schizophrenia. Mol Psychiatry, 4,163–72. https://doi.org/10.1038/sj.mp.4000473
• Aguilera, M., Arias, B., Wichers, M., Barrantes-Vidal, N., Moya, J. & Villa H. (2009). Early adversity and 5-HTT/BDNF genes: new evidence of gene-environment interactions on depressive symptoms in a general population. Psychol Med, 39, 1425–32. https://doi.org/10.1017/S0033291709005248
• Akiskal, H. S., & Pinto, O. (2000). The soft bipolar spectrum: footnotes to Kraepelin on the interface of hypomania, temperament and depression. In Bipolar disorders: 100 years after manic-depressive insanity. https://doi.org/10.1007/0-306-47521-9_2
• Aliyev, V. (2020). Major Depresif Bozukluğu Olan Hastalarda Farmakoterapinin Bilişsel İşlevler Üzerine Etkisi: Bir İzlem Çalışması [Yayınlanmamış Tıpta Uzmanlık Tezi]. Ankara Üniversitesi.
• Amerikan Psikiyatri Birliği, (2014). Ruhsal bozuklukların tanısal ve sayımsal el kitabı (DSM-5), Tanı ölçütleri el kitabı. (Çev: Köroğlu,E.) Hekimler Yayın Birliği.
• Angst, J. (1992). Epidemiology of depression. Psychopharmacology, 106(1), 71-74.
• Arslantaş, H., & Ergin, F. (2011). 50–65 yaş arasındaki bireylerde yalnızlık, depresyon, sosyal destek ve etki eden faktörler. Turkish Journal of Geriatrics, 14 (2) 135-144.
• Aşkın, R. (1999). Depresyonun genetiği, depresyon el kitabı. Roche Müstahzarları San. A.Ş.
• Aydın, E. (2018). Çocukluk çağı travmatik yaşantılarının psikolojik sağlamlık ve depresyon belirtileri üzerine etkisi [Yayımlanmamış Yüksek Lisans Tezi]. Fatih Sultan Mehmet Vakıf Üniversitesi.
• Aydın, R., Baytunca, M. B., & Erermiş, S. (2014). Pediatrik majör depresif bozukluğun genetik özellikleri. Pediatric Research, 1(4), 174-9. https://doi.org/10.4274/jpr.92486
• Bağdaçiçek, S. (2009). Majör depresyon ve panik bozukluğu olan hastaların erken disfonksiyonel şema aktivasyonlarının karşılaştırılması [Yayınlanmamış Uzmanlık Tezi]. Haydarpaşa Numune Eğitim ve Araştırma Hastanesi Psikiyatri Kliniği.
• Barbu, M. C., Shen, X., Walker, R. M., Howard, D. M., Evans, K. L., Whalley, H. C., ... & McIntosh, A. M. (2021). Epigenetic prediction of major depressive disorder. Molecular Psychiatry, 26(9), 5112-5123. https://doi.org/10.1038/s41380-020-0808-3
• Barraclough, B. M., Bunch, J., Nelson, B., & Sainsbury, P. (1974). A hundred cases of suicide: clinical aspects. The British Journal of Psychiatry, 125(587), 355-373. https://doi.org/10.1192/bjp.125.4.355
• Başoğul, C., & Buldukoğlu, K. (2015). Depresif bozukluklarda psikososyal girişimler. Psikiyatride Güncel Yaklaşımlar, 7(1), 1-15. https://doi.org/10.5455/cap.20140426072955
• Beck, A.T. (2006). Bilişsel terapi ve duygusal bozukluklar. (Çev: A, Türkcan). Litera Yayıncılık.
• Beck, A.T., Rush, A.J., Shaw, B.F., & Emery, G. (1987) Cognitive therapy of depression. Guilford Press.
• Blundell, J. E. (1984). Serotonin and appetite. Neuropharmacology, 23(12), 1537-1551. https://doi.org/10.1016/0028-3908(84)90098-4
• Border, R., Johnson, E.C., Evans, L.M., Smolen, A., Berley, N., Sullivan, P.F., & Keller, M.C. (2019). No support for historical candidate gene or candidate gene-by-interaction hypotheses for major depression across multiple large samples. American Journal of Psychiatry, 176(5), 376-387. https://doi.org/10.1176/appi.ajp.2018.18070881
• Bosker, F.J., Hartman, C.A., Nolte, I.M., Prins, B.P., Terpstra, P., Posthuma, D., ... & Nolen, W. A. (2011). Poor replication of candidate genes for major depressive disorder using genome-wide association data. Molecular Psychiatry, 16(5), 516-532. https://doi.org/10.1038/mp.2010.38
• Bromet, E., Andrade, L. H., Hwang, I., Sampson, N. A., Alonso, J., De Girolamo, G., … Kessler, R. C. (2011). Cross-national epidemiology of DSM-IV major depressive episode. BMC Medicine, 9(1), 90. https://doi.org/10.1186/1741-7015-9-90
• Brown, G. W., Bifulco, A., & Harris, T. (1987). Life events, vulnerability and onset of depression. British Journal of Psychiatry, 150(1), 30-42. https://doi.org/10.1192/bjp.150.1.30
• Butcher, J., Mineka, S., & Hooley, J. (2013). Anormal psikoloji. Kaknüs Psikoloji.
• Cai, N., Choi, K. W., & Fried, E. I. (2020). Reviewing the genetics of heterogeneity in depression: Operationalizations, manifestations and etiologies. Human Molecular Genetics, 29(R1), R10–R18. https://doi.org/10.1093/hmg/ddaa115
• Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W., Harrington, H., … Poulton, R. (2003). Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene. Science, 301(5631), 386–389. https://doi.org/10.1126/science.1083968
• Chahar Mahali S., Beshai S., Feeney J. R., Mishra S. (2020). Associations of negative cognitions, emotional regulation, and depression symptoms across four continents: International support for the cognitive model of depression. BMC Psychiatry, 20(1), 1–12. https://doi.org/10.1186/s12888-019-2423-x.
• Chapman, D. P., Whitfield, C. L., Felitti, V. J., Dube, S. R., Edwards, V. J., & Anda, R. F. (2004). Adverse childhood experiences and the risk of depressive disorders in adulthood. Journal of Affective Disorders, 82(2), 217–225. https://doi.org/10.1016/j.jad.2003.12.013
• Cimilli, C. (2001). Depresyonda sosyal ve kültürel etmenler. Çizgi Tıp Yayınevi.
• Cipriani, A., Barbui, C., Butler, R., Hatcher, S., & Geddes, J. (2011). Depression in adults: drug and physical treatments. BMJ clinical evidence, 2011.
• Collins, K. A., Westra, H. A., Dozois, D. J., & Burns, D. D. (2004). Gaps in accessing treatment for anxiety and depression: challenges for the delivery of care. Clinical Psychology Review, 24(5), 583-616. https://doi.org/10.1016/j.cpr.2004.06.001
• Çelik, F. H., & Hocaoğlu, Ç. (2016). Major depresif bozukluk tanımı, etyolojisi ve epidemiyolojisi: Bir gözden geçirme. Çağdaş Tıp Dergisi, 6(1), 51-66. https://doi.org/10.16899/ctd.03180
• D’Haenen, H., & Bossuyt, A. (1994). Dopamine D2 receptors in depression measured with single photon emission computed tomography. Biological Psychiatry, 35(2), 128–132. https://doi.org/10.1016/0006-3223(94)91202-5
• De Kloet, E. R., Joëls, M., & Holsboer, F. (2005). Stress and the brain: from adaptation to disease. Nature Reviews Neuroscience, 6(6), 463-475. https://doi.org/10.1038/nrn1683
• De Kloet, E.R., DeRijk, R.H., & Meijer, O.C. (2007). Therapy Insight: Is there an imbalanced response of mineralocorticoid and glucocorticoid receptors in depression? Nature Clinical Practice Endocrinology & Metabolism, 3(2), 168-179. https://doi.org/10.1038/ncpendmet0403
• Doğan, O., Gülmez, H., Ketenoğlu. C., & Kılıçkap, Z.Ö. (1995) Ruhsal bozuklukların epidemiyolojisi. Dilek Matbaası.
• Duncan, L.E., & Keller, M.C. (2011). A critical review of the first 10 years of candidate gene-by-environment interaction research in psychiatry. American Journal of Psychiatry, 168(10), 1041–1049. https://doi.org/10.1176/appi.ajp.2011.11020191
• Elias, E., Zhang, A. Y., & Manners, M.T. (2022). Novel pharmacological approaches to the treatment of depression. Life, 12(2), 196. https://doi.org/10.3390/life12020196
• Ersan, E., & Abay, E. (2001). Depresyonun genetik nedenleri. Duygudurum Dizisi. 6, 277-282.
• Eşel, E. (2002). Depresyondaki nöroendokrinolojik bulgular. Klinik Psikiyatri, 4, 35-50.
• Eser, B. (2019). Majör Depresif Bozukluk Tanısı Alan Hastalarda Depresif Belirti Şiddeti, Üstbilişler ve Obsesif İnanışlar Arasındaki İlişkiler [Yayımlanmamış Yüksek Lisans Tezi]. Çağ Üniversitesi.
• Fatemi, M., Hermann, A., Gowher, H., & Jeltsch, A. (2002). Dnmt3a and Dnmt1 functionally cooperate during de novo methylation of DNA. European Journal of Biochemistry, 269(20), 4981–4984. https://doi.org/10.1046/j.1432-1033.2002.03198.x
• Flint, J., & Kendler, K. S. (2014). The genetics of major depression. Neuron, 81(3), 484-503. https://doi.org/10.1016/j.neuron.2014.02.033
• Fried, E.I., Coomans, F., & Lorenzo-Luaces, L. (2020). The 341 737 ways of qualifying for the melancholic specifier. The Lancet Psychiatry, 7(6), 479-480. https://doi.org/10.1016/s2215-0366(20)30169-3
• Global Health Data Exchange (GHDx). Institute of Health Metrics and Evaluation. https://vizhub.healthdata.org/gbd-results/ (Accessed 4 December 2023).
• Glowinski, A.L., Madden, P.A.F., Bucholz, K.K., Lynskey, M., & Heath, A.C. (2003). Genetic epidemiology of self-reported lifetime DSM-IV major depressive disorder in a population-based twin sample of female adolescents. Journal of Child Psychology and Psychiatry, 44(7), 988–996. https://doi.org/10.1111/1469-7610.00183
• Gotlib, I. H., & Joormann, J. (2010). Cognition and depression: Current status and future directions. Annual Review of Clinical Psychology, 6, 285–312. https://doi.org/10.1146/annurev.clinpsy.121208.131305.
• Green, J. G., McLaughlin, K. A., Berglund, P. A., Gruber, M. J., Sampson, N. A., Zaslavsky, A. M., & Kessler, R. C. (2010). Childhood adversities and adult psychiatric disorders in the national comorbidity survey replication I: associations with first onset of DSM-IV disorders. Archives of General Psychiatry, 67(2), 113-123.https://doi.org/10.1001/archgenpsychiatry.2009.186
• Gülsün, M., Tamam, L., & Özçelik, F. (2012). Nöropeptid Y ve stres ilişkisi. Psikiyatride Güncel Yaklaşımlar, 4(1), 14-36. https://doi.org/10.5455/cap.20120402
• Hays, R.D., Wells, K. B., Sherbourne, C. D., Rogers, W., & Spritzer, K. (1995). Functioning and well-being outcomes of patients with depression compared with chronic general medical illnesses. Archives of General Psychiatry, 52(1), 11-19. https://doi.org/10.1001/archpsyc.1995.03950130011002
• Ho, T. C. (2019). Stress and neurodevelopment in adolescent depression. Biological psychiatry, 86(10), e33-e35. https://doi.org/10.1016/j.biopsych.2019.09.012
• Hodes, G. E., Walker, D. M., Labonté, B., Nestler, E. J., & Russo, S. J. (2017). Understanding the epigenetic basis of sex differences in depression. Journal of Neuroscience Research, 95(1–2), 692–702. https://doi.org/10.1002/jnr.23876
• Hofmann, S. G., Asnaani, A., Vonk, I. J., Sawyer, A. T., & Fang, A. (2012). The efficacy of cognitive behavioral therapy: A review of meta-analyses. Cognitive Therapy and Research, 36, 427-440. https://doi.org/10.1007/s10608-012-9476-1
• Howard, D. M., Adams, M. J., Clarke, T. K., Hafferty, J. D., Gibson, J., Shirali, M., … McIntosh, A. M. (2019). Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions. Nature Neuroscience, 22(3), 343–352. https://doi.org/10.1038/s41593-018-0326-7
• Hyde, C. L., Nagle, M. W., Tian, C., Chen, X., Paciga, S. A., Wendland, J. R., ... & Winslow, A. R. (2016). Identification of 15 genetic loci associated with risk of major depression in individuals of European descent. Nature Genetics, 48(9), 1031-1036. https://doi.org/10.1038/ng.3623
• Işık, E., Işık, U., & Taner, Y. (2013). Çoçuk, ergen, erişkin ve yaşlılarda depresif ve bipolar bozukluklar. Ziraat Gurup Matbaacılık.
• Jaber, M., Robinson, S. W., Missale, C., & Caron, M. G. (1996). Dopamine receptors and brain function. Neuropharmacology, 35(11), 1503–1519. https://doi.org/10.1016/s0028-3908(96)00100-1
• Karakaş, Ü., Çevik, K., Ay, M. E., Özdemir, G. D., Zıblak, A., Kenar, A. N. İ., ... & Erdal, M. E. (2023). Majör depresyon hastalarında BDNF gen polimorfizmi (rs6265) ile BDNF gen ekspresyon düzeylerinin araştırılması. Mersin Üniversitesi Sağlık Bilimleri Dergisi, 16(3), 473-482. https://doi.org/10.26559/mersinsbd.1271378
• Karamustafalıoğlu, O., & Yumrukçal, H. (2011). Depresyon ve anksiyete bozuklukları. Şişli Etfal Hastanesi Tıp Bülteni, 45(2), 65-74. http://www.anadoluissagligi.com/img/file_1370.pdf
• Kaufman, J., Yang, B. Z., Douglas-Palumberi, H., Grasso, D. J., Lipschitz, D. S., Houshyar, S., Krystal, J. H., & Gelernter, J. (2006). Brain-Derived Neurotrophic Factor–5-HTTLPR gene interactions and environmental modifiers of depression in children. Biological Psychiatry, 59(8), 673–680. https://doi.org/10.1016/j.biopsych.2005.10.026
• Keers, R., & Uher, R. (2012). Gene-environment interaction in major depression and antidepressant treatment response. Current Psychiatry Reports, 14(2), 129–137. https://doi.org/10.1007/s11920-011-0251-x
• Kendall, K. M., Van Assche, E., Andlauer, T. F. M., Choi, K. W., Luykx, J. J., Schulte, E. C., & Lu, Y. (2021). The genetic basis of major depression. Psychological Medicine, 51(13), 2217-2230. https://doi.org/10.1017/s0033291721000441
• Kendler, K. S., Ohlsson, H., Lichtenstein, P., Sundquist, J., & Sundquist, K. (2018). The genetic epidemiology of treated major depression in Sweden. American Journal of Psychiatry, 175(11), 1137-1144. https://doi.org/10.1176/appi.ajp.2018.17111251
• Kessler, R. C. (1997). The effects of stressful life events on depression. Annual review of Psychology, 48(1), 191-214. https://doi.org/10.1146/annurev.psych.48.1.191
• Kessler, R. C., & Bromet, E. J. (2013). The epidemiology of depression across cultures. Annual Review of Public Health, 34, 119-138. https://doi.org/10.1146/annurev-publhealth-031912-114409
• Kessler, R. C., Berglund, P. A., Dewit, D. J., Bedirhan Üstün, T., Wang, P. S., & Wïttchen, H. U. (2002). Distinguishing generalized anxiety disorder from major depression: prevalence and impairment from current pure and comorbid disorders in the US and Ontario. International Journal of Methods in Psychiatric Research, 11(3), 99-111. https://doi.org/10.1002/mpr.128
• Kessler, R. C., McGonagle, K. A., Zhao, S., Nelson, C. B., Hughes, M., Eshleman, S., ... & Kendler, K. S. (1994). Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States: results from the National Comorbidity Survey. Archives of General Psychiatry, 51(1), 8-9. https://doi.org/10.1001/archpsyc.1994.03950010008002
• Kessler, R. C., Walters, E. E., & Forthofer, M. S. (1998). The social consequences of psychiatric disorders, III: probability of marital stability. American Journal of Psychiatry, 155(8), 1092-1096. https://doi.org/10.1176/ajp.155.8.1092
• Krsteska, R., & Pejoska, V. (2013). The associatıon of poor economic condition and family relatıons in childhood with late-life depression. Psychiatria Danubina, 25 (3), 241-247. http://www.psychiatriadanubina.com/UserDocsImages/pdf/dnb_vol25_no3/dnb_vol25_no3_241.pdf
• Kwak, Y. T., Yang, Y. S., & Koo, M.S. (2016). Depression and cognition. Dement Neurocogn Disord, 15, 103–109. https://doi.org/10.12779/dnd.2016.15.4.103
• Labermaier, C., Masana, M., & Müller, M. B. (2013). Biomarkers Predicting antidepressant treatment response: How can we advance the field? Disease Markers, 35, 23-31. https://doi.org/10.1155/2013/984845
• LaPlant, Q., Vialou, V., Covington, H.E., … & Nestler, E. J. (2010). Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens. Nat. Neurosci. 13, 1137-1143. https://doi.org/10.1038/nn.2619
• Li, Z., Chen, J., Yu, H., He, L., Xu, Y., Zhang, D., ... & Shi, Y. (2017). Genome-wide association analysis identifies 30 new susceptibility loci for schizophrenia. Nature Genetics, 49(11), 1576-1583. https://doi.org/10.1038/ng.3973
• Lin, Y. L., & Wang, S. (2014). Prenatal lipopolysaccharide exposure increases depression-like behaviors and reduces hippocampal neurogenesis in adult rats. Behavioural Brain Research, 259, 24–34. https://doi.org/10.1016/j.bbr.2013.10.034
• Lohoff, F. W. (2010). Overview of the genetics of major depressive disorder. Current Psychiatry Reports, 12(6), 539–546. https://doi.org/10.1007/s11920-010-0150-6
• Lopizzo, N., Bocchio Chiavetto, L., Cattane, N., Plazzotta, G., Tarazi, F.I., Pariante, C.M., Riva, M.A., & Cattaneo, A. (2015). Gene–environment interaction in major depression: focus on experience-dependent biological systems. Frontiers in Psychiatry, 6. https://doi.org/10.3389/fpsyt.2015.00068
• Magdalene, C., Jawahar., Catherine, Toben., Bernhard, T. & Baune. (2019). Gene-environment ınteractions and epigenetic mechanisms in depression. Neurobiology of Depression, 17-25. https://doi.org/10.1016/B978-0-12-813333-0.00003-2
• Malhi, G. S., & Mann, J. J. (2018). Depression. The Lancet, 392, 2299–2312. https://doi.org/10.1016/s0140-6736(18)31948-2
• McGuffin, P., Cohen, S., & Knight, J. (2007). Homing in on depression genes. American Journal of Psychiatry, 164(2), 195-197. https://doi.org/10.1176/ajp.2007.164.2.195
• McIntosh, A. M., Sullivan, P. F., & Lewis, C. M. (2019). Uncovering the genetic architecture of major depression. Neuron, 102(1), 91–103. https://doi.org/10.1016/j.neuron.2019.03.022
• McIntosh, E., Gillanders, D., & Rodgers, S. (2010). Rumination, goal linking, daily hassles and life events in major depression. Clinical psychology & psychotherapy, 17(1), 33-43. https://doi.org/10.1002/cpp.611
• McIntyre, R. S., & O'Donovan, C. (2004). The human cost of not achieving full remission in depression. Canadian Journal of Psychiatry, 49(1), 10-16.
• McLaughlin, K. A., Conron, K. J., Koenen, K. C., & Gilman, S. E. (2010). Childhood adversity, adult stressful life events, and risk of past-year psychiatric disorder: a test of the stress sensitization hypothesis in a population-based sample of adults. Psychological Medicine, 40(10), 1647-1658. https://doi.org/10.1017/s0033291709992121
• Meltzer, H. Y. & Lowy, M. T. (1987). The serotonin hypothesis of depression. In Psychopharmacology. Raven Press.
• Meltzer, H. Y., Umberkoman-Wiita, B., Robertson, A., Tricou, B. J., Lowy, M., & Perline, R. (1984). Effect of 5-hydroxytryptophan on serum cortisol levels in major affective disorders: I. Enhanced response in depression and mania. Archives of General Psychiatry, 41(4), 366-374. https://doi.org/10.1001/archpsyc.1984.01790150056009
• Menke, A., Klengel, T., & B Binder, E. (2012). Epigenetics, depression and antidepressant treatment. Current Pharmaceutical Design, 18(36), 5879-5889. https://doi.org/10.2174/138161212803523590
• Murdock, N. L. (2012). Theories of counseling and psychotherapy: a case approach. Pearson Higher Ed.
• Murgatroyd, C., Patchev, A. V., Wu, Y., Micale, V., Bockmühl, Y., Fischer, D., Holsboer, F., Wotjak, C. T., Almeida, O. F. X., & Spengler, D. (2009). Dynamic DNA methylation programs persistent adverse effects of early-life stress. Nature Neuroscience, 12(12), 1559–1566. https://doi.org/10.1038/nn.2436
• Nanni, V., Uher, R., & Danese, A. (2012). Childhood maltreatment predicts unfavorable course of illness and treatment outcome in depression: a meta-analysis. American Journal of Psychiatry, 169(2), 141-151. https://doi.org/10.1176/appi.ajp.2011.11020335
• Ni, G., van der Werf, J., Zhou, X., Hyppönen, E., Wray, N. R., & Lee, S. H. (2019). Genotype–covariate correlation and interaction disentangled by a whole-genome multivariate reaction norm model. Nature Communications, 10(1), 1-15. https://doi.org/10.1038/s41467-019-10128-w
• Noble, R. E. (2005). Depression in women. Metabolism, 54(5), 49-52. https://doi.org/10.1016/j.metabol.2005.01.014
• Olchanski, N., McInnis Myers, M., Halseth, M., Cyr, P. L., Bockstedt, L., Goss, T. F., & Howland, R. H. (2013). The economic burden of treatment-resistant depression. Clinical therapeutics, 35(4), 512-522. https://doi.org/10.1016/j.clinthera.2012.09.001
• Oldehinkel, A. J., Wittchen, H. U., & Schuster, P. (1999). Prevalence, 20-month incidence and outcome of unipolar depressive disorders in a community sample of adolescents. Psychological Medicine, 29(3), 655-668. https://doi.org/10.1017/s0033291799008454
• Özdel, L., Bostancı, M., Özdel, O., & Oğuzhanoğlu, N. K. (2002). Üniversite öğrencilerinde depresif belirtiler ve sosyodemografik özelliklerle ilişkisi. Anadolu Psikiyatri Dergisi, 3(3), 155-161.
• Özgüç, S. (2020). Depresyon hastalarına verilen üstbiliş eğitiminin depresyon ve bilişsel çarpıtma düzeylerine etkisi [Yayımlanmamış Doktora Tezi]. Gaziantep Üniversitesi.
• Özgür, E., Tığlı, H., & Tığlı, H. (2020). İnsan hastalıklarında epigenetiğin rolüne klinik bakış. İstanbul Gelişim Üniversitesi Sağlık Bilimleri Dergisi, 10, 107-122.
• Polderman, T. J., Benyamin, B., De Leeuw, C. A., Sullivan, P. F., Van Bochoven, A., Visscher, P. M., & Posthuma, D. (2015). Meta-analysis of the heritability of human traits based on fifty years of twin studies. Nature Genetics, 47(7), 702-709. https://doi.org/10.1038/ng.3285
• Renner, F., Arntz, A., Leeuw, I., & Huibers, M. J. (2013). Treatment for chronic depression using schema therapy. Clinical Psychology-science and Practice, 20(2), 166–180. https://doi.org/10.1111/cpsp.12032
• Rice, F. (2010). Genetics of childhood and adolescent depression: insights into etiological heterogeneity and challenges for future genomic research. Genome Medicine, 2(9), 68. https://doi.org/10.1186/gm189
• Rice, S. M., Fallon, B. J., Aucote, H. M., Möller-Leimkühler, A., Treeby, M. S., & Amminger, G. P. (2015). Longitudinal sex differences of externalising and internalising depression symptom trajectories: Implications for assessment of depression in men from an online study. International Journal of Social Psychiatry, 61(3), 236-240. https://doi.org/10.1177/0020764014540149
• Rihmer, Z., & Angst, J. (2007). Duygudurum Bozuklukları: Epidemiyoloji. In: Sadock B, Sadock V,eds. Aydın H, Bozkurt A, (çev. eds). Türkçe: Kaplan & Sadock’s Comprehensive Text book of Psychiatry. 8. Baskı. Öncü Basımevi.
• Roos, E., Burström, B., Saastamoinen, P. & Lahelma, E. (2005). A comparative study of the patterning of women’s health by family status and employment status in Finland and Sweden. Social Science Medicine, 60, 2443-2451. https://doi.org/10.1016/j.socscimed.2004.11.020
• Sadock, B. J., & Sadock, V. (2007). Kaplan & Sadock’s Comprehensive Textbook of Psychiatry II. cilt. Çeviri: Aydın H, Bozkurt A. Ankara: Güneş Kitapevi, 1498-1580. Schou M (1999) The early European lithium studies. Aust NZJ Psychiatry, 33, Suppl: 39-47.
• Schaaf, M. J. M., De Kloet, E. R., & Vreugdenhil, E. (2000). Corticosterone effects on BDNF expression in the hippocampus Implications for memory formation. Stress, 3(3), 201-208. https://doi.org/10.3109/10253890009001124
• Schroeder, M., Hillemacher, T., Bleich, S., & Frieling, H. (2012). The Epigenetic Code in Depression: Implications for treatment. Clinical Pharmacology & Therapeutics, 91(2), 310–314. https://doi.org/10.1038/clpt.2011.282
• Sharf, R.S. (2012). Theories of Psychotherapy and Counseling: Concepts and Cases. (5th ed.). Cengage Learning Products.
• Shen, X., Howard, D. M., Adams, M. J., Hill, W. D., Clarke, T. K., Deary, I. J., … McIntosh, A. M. (2020). A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank. Nature Communications, 11(1), 1–16. https://doi.org/10.1038/s41467-020-16022-0
• Soysal, A. Ş., & Uzbay, İ. T. (2006). Beyin ödüllendirme sistemi majör depresyon tedavisinde yeni bir hedef olabilir mi?. New/Yeni Symposium Journal, 44(1), 3-13.
• Sullivan, P. F., Neale, M. C., & Kendler, K. S. (2000). Genetic epidemiology of major depression: Review and meta-analysis. American Journal of Psychiatry, 157(10), 1552-1562. https://doi.org/10.1176/appi.ajp.157.10.1552
• Tamam, L., & Zeren, T. (2002). Depresyonda serotonerjik düzenekler. Klinik Psikiyatri Dergisi, 5, 11-18. https://www.klinikpsikiyatri.org/jvi.aspx?pdir=kpd&plng=tur&un=KPD-72289
• Taşğın, E., & Çetin, Ç. F. (2006). Ergenlerde major depresyon: Risk etkenleri, koruyucu etkenler ve dayanıklılık. Çocuk ve Gençlik Ruh Sağlığı Dergisi, 13(2), 87-93. http://cms.galenos.com.tr/Uploads/Article_30297/cogepderg-13-87.pdf
• Teslovich, T. M., Musunuru, K., Smith, A. V., Edmondson, A. C., Stylianou, I. M., Koseki, M., ... & Dominiczak, A. F. (2010). Biological, clinical and population relevance of 95 loci for blood lipids. Nature, 466(7307), 707-713.
• Torun, Ö. D. (2019). Majör depresif bozukluk tanısı almış bir grup hastada üstbilişsel işlevlerin incelenmesi [Yayımlanmamış Yüksek Lisans Tezi]. Çağ Üniversitesi.
• Uchida, S., Yamagata, H., Seki, T., & Watanabe, Y. (2017). Epigenetic mechanisms of major depression: Targeting neuronal plasticity. Psychiatry and Clinical Neurosciences, 72(4), 212-227. https://doi.org/10.1111/pcn.12621
• Uher, R. (2011). Genes, environment, and individual differences in responding to treatment for depression. Harvard Review of Psychiatry, 19(3), 109-124. https://doi.org/10.3109/10673229.2011.586551
• Ünal S., ve Özcan E. (2000). Depresyonda hazırlayıcı, ortaya çıkarıcı ve koruyucu etkenler. Anadolu Psikiyatri Dergisi, 1(1), 41-47. https://www.alpha-psychiatry.com/Content/files/sayilar/167/41-48.pdf
• Ünal, S., Küey, L., Güleç, C., Bekaroğlu, M., Evlice, Y. E., & Kırlı, S. (2002). Depresif bozukluklarda risk etkenleri. Klinik Psikiyatri, 5(1), 8-15. https://jag.journalagent.com/kpd/pdfs/KPD_5_1_8_15.pdf
• Van Assche, E., Moons, T., Cinar, O., Viechtbauer, W., Oldehinkel, A. J., Van Leeuwen, K., … van Winkel, R. (2017). Gene-based interaction analysis shows GABA ergic genes interacting with parenting in adolescent depressive symptoms. Journal of Child Psychology and Psychiatry, 58(12), 1301–1309. https://doi.org/10.1111/jcpp.12766
• Van der Auwera, S., Peyrot, W. J., Milaneschi, Y., Hertel, J., Baune, B., Breen, G., ... & Grabe, H. (2018). Genome‐wide gene‐environment interaction in depression: A systematic evaluation of candidate genes: The childhood trauma working‐group of PGC‐MDD. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 177(1), 40-49. https://doi.org/10.1002/ajmg.b.32593
• Widom, C. S., DuMont, K., & Czaja, S. J. (2007). A prospective investigation of major depressive disorder and comorbidity in abused and neglected children grown up. Archives of General Psychiatry, 64(1), 49. https://doi.org/10.1001/archpsyc.64.1.49
• Winer, E., Salem, T., Bartoszek, G. & Snodgrass, M. (2015). Major depressive disorder. The Encyclopedia of Clinical Psychology, 1-9. https://doi.org/10.1002/9781118625392.wbecp433
• Wray, N. R., Ripke, S., Mattheisen, M., Trzaskowski, M., Byrne, E. M., Abdellaoui, A., ... & Viktorin, A. (2018). Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. Nature Genetics, 50(5), 668-681. https://doi.org/10.1038/s41588-018-0090-3
• Yarım, G., & Kazak, F. (2015). Beyin kaynaklı nörotrofik faktör. Atatürk Üniversitesi Veteriner Bilimleri Dergisi, 10(2), 120-129. https://doi.org/10.17094 / avbd.02290
• Yehuda, R., McFarlane, A. C., & Shalev, A. Y. (1998). Predicting the development of posttraumatic stress disorder from the acute response to a traumatic event. Biol. Psychiatry, 44, 1305-1313. https://www.psychiatry.wisc.edu/courses/Nitschke/seminar/yehuda%20et%20al%20bio%20psychiatry%201998.pdf
• Yıldız, M., & Duy, B. (2015). Sokakta çalışmak ve gelir düzeyi erinlerin benlik saygısı, yaşam doyumu ve depresyon düzeylerine etki eder mi? (Diyarbakır ili örneği). Elementary Education Online, 14(2). http://ilkogretim-online.org.tr/index.php/io/article/view/1289/1145
• Young, J. E., Klosko, J. S., & Weishaar, M. E. (2009). Şema terapi. Litera Yayıncılık.
• Zhao, M. Z., Song, X. S., & Ma, J. S. (2021). Genexenvironment interaction in major depressive disorder. World Journal of Clinical Cases, 9(31), 9368-9375. https://doi.org/10.12998/wjcc.v9.i31.9368