Epigenetic markers in inflammation-related genes associated with mood disorder: a cross-sectional and longitudinal study in high-risk offspring of bipolar parents.
Duffy A., Goodday SM., Keown-Stoneman C., Scotti M., Maitra M., Nagy C., Horrocks J., Turecki G.
Bipolar disorder is highly heritable and typically onsets in late adolescence or early adulthood. Evidence suggests that immune activation may be a mediating pathway between genetic predisposition and onset of mood disorders. Building on a prior study of mRNA and protein levels in high-risk offspring published in this Journal, we conducted a preliminary examination of methylation profiles in candidate immune genes from a subsample of well-characterized emergent adult (mean 20 years) offspring of bipolar parents from the Canadian Flourish high-risk cohort. Models were adjusted for variable age at DNA collection, sex and antidepressant and mood stabilizer use. On cross-sectional analysis, there was evidence of higher methylation rates for BDNF-1 in high-risk offspring affected (n = 27) and unaffected (n = 23) for mood disorder compared to controls (n = 24) and higher methylation rates in affected high-risk offspring for NR3C1 compared to controls. Longitudinal analyses (25 to 34 months) provided evidence of steeper decline in methylation rates in controls (n = 24) for NR3C1 compared to affected (n = 15) and unaffected (n = 11) high-risk offspring and for BDNF-2 compared to affected high-risk. There was insufficient evidence that changes in any of the candidate gene methylation rates were associated with illness recurrence in high-risk offspring. While preliminary, findings suggest that longitudinal investigation of epigenetic markers in well-characterized high-risk individuals over the peak period of risk may be informative to understand the emergence of bipolar disorder.