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

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

doi: 10.1097/YPG.0000000000000196

Background 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.

Participants and methods 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.

Results We found a significant inverse correlation between MTHFR methylation levels and perceived stress scores (r=−0.502; P=5.9×10−5), which remained significant after being adjusted for age, sex, and depressive symptomatology.

Conclusion 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.

Laboratory of NeuroPsychiatric Genetics, Biomedical Sciences Research Group, School of Medicine, Universidad Antonio Nariño, Bogotá, Colombia

Correspondence to Diego A. Forero, MD, PhD, Laboratory of NeuroPsychiatric Genetics, School of Medicine, Antonio Nariño University, Bogotá 110231, Colombia Tel: +57 313 261 0427; fax: +57 13 405 871; e-mail:

Received March 29, 2017

Received in revised form November 9, 2017

Accepted March 5, 2018

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