DNA methylation studies of depression with onset in the peripartum: A critical systematic review

Abstract Objective Major depression with peripartum onset (MDP) has been associated with multiple adverse offspring health outcomes. The biological mechanisms underlying this relationship remain unclear, but DNA methylation (DNAm) represents a plausible mechanism for mediating MDP exposures and changes in offspring development, behavior, and health. Advances in DNAm research necessitate reevaluating the MDP-DNAm literature to determine how well past studies conform with current best practices. Method Five databases were searched to identify studies of prenatal-onset MDP and DNAm. Quality scores were assigned to each article independently by two raters using a novel scale specific for MDP-DNAm research. Results Nineteen studies met inclusion criteria. Quality scores ranged from 10 to 17 out of 24 points ( M  = 12.8; SD = 1.9), with higher scores indicating increased study rigor. Poor covariate reporting was the most significant contributor to lower scores. Conclusion No longitudinal MDP-DNAm studies exist. Earlier MDP-DNAm studies should be interpreted with caution, and future research must commit to sharing methodology and data to facilitate cross-study comparisons and maximize dataset utility.