Prenatal Programming of Psychopathology: The Role of Epigenetic Mechanisms / PRENATALNO PROGRAMIRANJE PSIHIJATRIJSKIH POREMEĆAJA: ULOGA EPIGENETSKIH MEHANIZAMA

Summary The Human Genome Project, completed ten years ago, widely opened the door for the field of Epigenetics as a new venue to study the causes of human disease and to search for predictive biomarkers and therapeutic targets for a wide range of disorders. The field of behavioral and psychiatric epigenetics is still very young, but increasing evidence suggests that epigenetic mechanisms contribute to the development of neuropsychiatric disorders. The prenatal period is particularly vulnerable to epigenetic disruption, and it seems likely that adverse in utero environments can induce epigenetic dysregulation and predispose an individual to mental disease later in life. Emerging evidence from animal studies has shown that maternal exposure to drugs, stress, and toxicants can alter epigenetic gene programming in the brain and contribute to neurodevelopmental and behavioral deficits in the offspring. The evidence from human studies is more limited but is in agreement with animal data. Several human studies have shown that prenatal risk factors, such as maternal food deprivation and stressful life events, are associated with persistent epigenetic changes in genes that are linked to neurodevelopmental disorders and psychopathology. Although these studies support the hypothesis that epigenetic mechanisms may be involved in prenatal programming of psychopathology, a collaborative effort of basic, clinical and epidemiological research is needed to advance this field. Nevertheless, this field holds great promise to facilitate our understanding of environmental contribution to human mental disease and to reveal new predictive biomarkers as well as preventive and therapeutic approaches for various neuropsychiatric disorders. Kratak sadržaj Projekat humanog genoma (HGP), završen pre deset godina, širom je otvorio vrata epigenetici kao novoj oblasti za prou- čavanje uzroka humanih bolesti i za pronalaženje novih dijag- nostičkih biomarkera i terapeutskih pristupa za širok spektar poremećaja. Epigenetika ponašanja i psihijatrijska epigene- tika su još uvek mlade oblasti ali je sve više dokaza koji ukazu- ju na to da epigenetski mehanizmi doprinose razvoju neuro- psihijatrijskih poremećaja. Prenatalni period je posebno osetljiv i smatra se da negativni uslovi tokom intrauterinog razvoja mogu da izazovu epigenetsku disregulaciju i predis- poniraju osobu za razvoj duševnih bolesti kasnije u životu. Istraživanja na životinjama pokazala su da izlaganje majke lekovima, stresu i otrovnim materijama može da prameni epi- genetsko programiranje gena u mozgu i da doprinese pore- mećajima razvoja mozga i ponašanja kod potomaka. Istra- živanja na ljudima su znatno ograničenija, ali su rezultati u skladu sa podacima dobijenim kod životinja. Nekoliko študija na ljudima ukazuje na to da su prenatalni faktori rizika, kao što su gladovanje majke ili izlaganje majke stresu, povezani sa trajnim epigenetskim promenama u genima koji su dove- deni u vezu sa neurorazvojnim poremećajima i psihopatološ- kim promenama. lako ove študije podržavaju hipotezu da epigenetski mehanizmi mogu biti uključeni u prenatalno pro- gramiranje psihijatrijskih oboljenja, potreban je zajednički na- por istraživača iz osnovnih, kliničkih i epidemioloških istra- živanja da bi se ova oblast unapredila. Ovo polje istraživanja omogućiće nam da bolje razumemo doprinos životne sredine razvoju mentalnih bolesti kod ljudi i ima potencijal da otkrije nove biomarkere, kao i preventivne i terapeutske pristupe različitim neuropsihijatrijskim poremećajima.