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Abstract

Depression occurs in 15% of pregnant women and 1/3 are taking selective serotonin reuptake inhibitors (SSRIs) as antidepressants. The neurotransmitter, serotonin, plays a critical role in modulating stress responses and early brain development. Serotonin transporter (SLC6A4) regulates extracellular serotonin levels, and an insertion/deletion variant in the promoter (5HTTLPR) is associated with depression. Maternal mood and SSRIs may program newborns’ behaviour later in life. The underlying molecular mechanism for developmental programming may involve DNA methylation, which requires methyl nutrients as enzymatic cofactors. While low methyl nutrient status (folate and vitamin B₁₂) and a genetic variant in methylenetetrahydrofolate reductase (MTHFR C677T) have been associated with depression in adults, the role of methyl nutrient metabolism in depression during pregnancy remains unclear. Furthermore, little is known about the combined roles of methyl nutrient status and depression in the epigenetic regulation of SLC6A4. The experiments in this thesis explored whether disturbances in methyl nutrient metabolism and depressed mood during the 3rd trimester of pregnancy affect SLC6A4 methylation and expression in mothers and their newborns. Maternal folate status was positively associated with maternal SLC6A4 methylation at CpGs 1, 4, and 8 (P