We then turned our attention to the relationship between the lifetime history of MD or AD and both SLC6A4 methylation and gene expression. There was a trend for those without a lifetime history of MD, but not AD, to have higher amounts of total methylation than those without a history of depression (P < 0.07; ANOVA; 17.3% in those with MD vs. 15.6% in those without MD). However, when male and female samples are analyzed separately, the findings were nominally, but not significantly different (15.8% in males with a lifetime MD vs. 14.4% in those without lifetime MD, P < 0.25; ANOVA, 18.1% in females with lifetime MD vs. 17.2% in those without lifetime MD, P < 0.52). There were no significant relationships between the expression of SLC6A4 by either probe and lifetime history of MD. However, lifetime history of AD was associated with increased expression of SLC6A4 as measured by both the exon 1 (P < 0.03) and exon 8 (P < 0.04) probes (data not shown).
