MTHFR methylation, serum cholesterol and depression in children experiencing psychosocial stress

• In Event: 2-122 - From child conception to adulthood: why epigenetic data analysis should be integrated into longitudinal studies

Integrative Statement

Depression is associated with stressful environments and dietary factors. Stress and nutrition, in turn, are associated with epigenetics. Serum cholesterol, which is prone to dietary influences, has been linked to symptoms of depression. This relationship may be (in part) due to altered epigenetic regulation of Methylenetetrahydrofolate Reductase (MTHFR). MTHFR codes for the MTHFR enzyme, which has diverse metabolic functions, has recently been linked with both depression and serum cholesterol levels. Moreover, research indicates that psychosocial stressors may moderate the relationship between cholesterol and MTHFR. In 510 mother-child pairs, we examined between-group contrasts of children exposed to high- or low- psychosocial stressors (pregnancy through 11 years) in the prospective relationships between maternal (pregnancy) and child (7 years) serum cholesterol, MTHFR DNA methylation (birth, 7 years), and development of depression symptoms from 8-15 years. After adjusting for potential confounding, we had three main findings. First, for high- and low-psychosocial stress trajectory groups (see Figure 1), higher prenatal cholesterol was associated with higher MTHFR methylation at birth (see Figure 2). Second, there was continuity for both cholesterol and MTHFR methylation over time for both groups. Third, for high-stress but not low-stress exposed children, higher age 7 MTHFR methylation was associated with higher initial symptoms of depression symptoms at age 8, and with lower changes in depression symptoms from ages 10-15. Overall, our findings provide evidence for a synergistic relationship between prenatal cholesterol, MTHFR methylation, and symptoms of depression in children.

Authors

• Maurissa S.C. Mesirow, King's College London
  Non-Presenting Author

• Charlotte Cecil, University of Bristol
  Non-Presenting Author

• Barbara Maughan, King's College London
  Non-Presenting Author

• Felice Jacka, Deakin University
  Non-Presenting Author

• Caroline Relton, University of Bristol
  Non-Presenting Author

• Edward Dylan Barker, King's College London
  Presenting Author