MTHFR gene methylation is associated with perceived stress in healthy young adults

Karen M. Jiménez, Angela J. Pereira-Morales, Diego A. Forero

Epigenetic factors have been identified in the past years as interesting candidates for psychiatric disorders and related endophenotypes. It has been found that the methylenetetrahydrofolate reductase (MTHFR) gene is associated with major depressive disorder, and the aim of the current study was to examine the possible association between perceived stress and MTHFR methylation, taking into account depressive symptoms as a covariate. Seventy-eight healthy Colombian participants (mean age=20.9 years; SD=3.0) were evaluated with the Perceived Stress Scale and with the Patient Health Questionnaire-9 for depressive symptomatology. MTHFR methylation levels were measured with a methylation-sensitive high-resolution melting method. A multiple regression analysis (adjusting for age, sex, and depressive symptoms) was carried out to assess the association between MTHFR methylation and perceived stress scores. We found a significant inverse correlation between MTHFR methylation levels and perceived stress scores (r=-0.502; P=5.9×10), which remained significant after being adjusted for age, sex, and depressive symptomatology. To our knowledge, this is the first study that reports an association between perceived stress and MTHFR methylation levels. This report adds evidence to the emerging role of epigenetic changes in endophenotypes related to affective disorders.