Epigenetic markers in inflammation-related genes associated with mood disorder: a cross-sectional and longitudinal study in high-risk offspring of bipolar parents

Journal article

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.

Authors: Duffy, A; Goodday, S; Keown-Stoneman, C; Scotti, M; Maitra, M

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer Nature
• Journal: International Journal of Bipolar Disorders
• Volume: 7
• Issue: 1
• Article number: 17
• Publication date: 2019-08-06
• Acceptance date: 2019-07-01
• DOI: 10.1186/s40345-019-0152-1
• ISSN: 2194-7511
• Pmid: 31385059
• Language: English
• Keywords: FFR