Browsing by Subject "glukokortikoidi"

Stressful environments can affect human behaviour and physiology through epigenetic mechanisms possibly in an age-dependent manner. Epigenetic mechanisms, such as DNA methylation, can activate or inhibit gene expression. Stressful experiences can lead to methylation changes and thus relay environmental effects to an individual’s phenotype. This thesis examines the relationship between an individual’s methylation profile and stressful life events encountered during the prenatal period, childhood and adulthood. Increased methylation in the NR3C1 gene, which has been linked to the hypothalamus-pituitary-adrenal (HPA) axis, has been associated with stressful childhood experiences in single gene studies. However, the relationship between NR3C1 gene methylation and stressful experiences has been contradictory in studies that have focused on the prenatal period. These conflicting results might be explained by issues related to sample sizes. In genome wide association studies, no relationship has been found between NR3C1 gene methylation and stressful life events. Stressful life events have been found to increase mean methylation levels of the promoter region of SERT gene, which has been linked to depression. The 5-HTTLPR region of SERT and methylation of SERT promoter might regulate SERT expression and thus predispose an individual to depression. On the other hand, it is possible that another epigenetic mechanism (e.g. histone acetylation) regulates SERT expression. Stressful childhood and adulthood experiences have been linked to increased methylation levels of various genes in genome-wide association studies. Yet, studies have failed to find a specific gene whose methylation levels would be repeatedly linked to stressful experiences. Some genome studies have found no relationship between methylation levels and stressful prenatal or early childhood experiences. Conflicting results between studies might be due to methodological issues or differences in sample sizes. Traumatic adulthood experiences have been linked to increased methylation levels across the genome while post-traumatic stress disorder (PTSD) symptoms have been associated with decreased methylation levels. It is possible that increased methylation of genes related to the HPA axis might protect an individual from PTSD symptoms after traumatic event. Stressful environments might alter an individual’s methylation profile and thus lead to various psychopathological states. However, these changes in methylation profiles might be reversible. Additional research focusing on the relationship between stressful life events and methylation profiles can lead to the development of different epigenetic therapies in the future.