Psikopatolojilerde gen-çevre etkileşimi: Stresle ilgili genetik ve epigenetik süreçler

Stresli yaşam olaylarının birçok psikolojik problemle ilişki içinde olduğu uzun zamandır bilinmektedir. Stres ve psikiyatrik rahatsızlıklar arasındaki ilişki, biyolojik ve çevresel faktörlerin etkileşimlerini inceleyen çalışmalar sonucunda daha anlaşılır hale gelmektedir. Bu makalede, insan vücudundaki genetik ve epigenetik süreçleri içeren biyolojik mekanizmalar aracılığıyla psikopatolojiler üzerinde etkili olan stresle ilişkili çevresel faktörlere değinilmektedir. Otonom sinir sistemi ve hipotalamus- hipofiz-adrenal aksı gibi zihin sağlığı ve stres yönetimi açısından önemli yapıların işleyişinde rol alan genler üzerindeki tek nükleotid polimorfizmleri ve DNA metilasyonları, psikopatolojilerdeki gen-çevre etkileşimi mekanizmalarına ışık tutmaktadır. Erken ve yakın dönem olumsuz çevresel yaşantıların biyolojik süreçler ile bağlantılı bir biçimde psikiyatrik rahatsızlıklarla olan ilişkisine yönelik bulgular dikkat çekicidir. Özellikle, CRHR1, FKBP5, CRHBP, SLC6A4, NR3C1, OXTR ve BDNF gibi stresle ilgili genlerin depresyon, intihar, bipolar bozukluk, kaygı bozukluğu, çeşitli kişilik bozuklukları ve travma sonrası stres bozukluğu gibi çok sayıda psikiyatrik problemle ilişkisi çevresel yaşantılarla etkileşim içerisinde rapor edilmiştir. Söz konusu ilişkilerin bu problemlere yönelik tedavi yaklaşımlarının etkinliğinde rol oynadığını gösteren çalışmalar hızla artmaktadır. Bulgular yorumlanırken göz önünde bulundurulması gereken olası kısıtlılıklar ve gelecek çalışmalar için öneriler tartışılmıştır.

Gene-environment interaction in psychopathologies: Stress-related genetic and epigenetic influences

It has long been known that stressful life events are related to various psychological problems. The relationship between stress and psychiatric disorders has been further recognized due to reports of studies investigating interactions between biological and environmental factors. This paper is about the effect of stress-related environmental factors on psychopathologies through relevant biological mechanisms, such as genetic and epigenetic processes, in human body. Single-nucleotide polymorphisms and DNA methylation profiles of the genes playing role in the autonomic nervous system and the hypothalamic-pituitary-adrenal axis, which are essential for mental health and stress regulation, shed light upon gene-environment interactions in psychopathologies. Research results showing an association between early/late adversities and psychiatric problems through biological mechanisms deserve note. Relationships between genes related to stress regulation, such as CRHR1, FKBP5, CRHBP, SLC6A4, NR3C1, OXTR and BDNF, and various psychiatric conditions (e.g., depression, suicide, anxiety, bipolar disorder, personality disorders and post-traumatic stress disorder) have been suggested in an interaction with environmental factors. The number of studies reporting similar associations for therapeutic approaches to these disorders is also on the increase. Possible limitations when interpreting findings and suggestions for future research have also been discussed.

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