EPIGENETIC BIOMARKERS IN POSTPARTUM DEPRESSION AND POSTPARTUM PSYCHOSIS

We previously identified epigenetic biomarker patterns at genes that are predictive of “reproductive” mood disorders including postpartum depression (PPD) and premenstrual dysphoric disorder (PMDD). We originally investigated estrogen mediated epigenetic reprogramming events in the hippocampus and risk for PPD using a cross species translational design. We identified two genetic loci, HP1BP3 and TTC9B, which were modified by estrogen exposure in the rodent model and were also prospectively predictive of PPD in antenatal blood in pregnant women who later developed PPD. These same epigenetic biomarkers were also found to be present in women with PMDD who were also responsive to selective serotonin reuptake inhibitors. Postpartum psychosis (PP) is another reproductive mood disorder which presents with manic, depressive or mixed symptoms with psychosis shortly after delivery. We investigated whether our epigenetic biomarkers were also found in women with PP and conducted an epigenome-wide association study (EWAS) to assess whether epigenetic changes were predictive of either type of psychiatric symptoms or recurrence of psychiatric illness outside of the postpartum time period. We found that our previously identified epigenetic biomarkers were NOT associated with PP, indicating that PPD and PP have separate underlying biological mechanisms. We also identified multiple (912) epigenetic changes statistically associated with depressive symptoms, but no epigenetic changes were statistically associated with either manic or psychotic symptoms. We also identified epigenetic changes that were associated with future psychiatric relapse outside of the postpartum time period, though the follow-up period was limited to 4 years. Future research will include identifying the underlying pathophysiology of central nervous system sensitivity to reproductive hormone change as well as further developing the identified epigenetic changes associated with psychiatric relapse outside of the postpartum time-period in women with PP by extending the length of follow-up. Development of blood tests that are predictive of a future mental illness or future course of psychiatric illness has the potential to move psychiatry from a reactive approach to a preventative one and to reduce stigma surrounding mental illness in general.

References

Guintivano J, Arad M, Gould TD, Payne JL, Kaminsky ZA. Antenatal prediction of postpartum depression with blood DNA methylation biomarkers. Mol Psychiatry. 2014; 19(5):633. Payne JL, Osborne LM, Cox O, et al. DNA methylation biomarkers prospectively predict both antenatal and postpartum depression. Psychiatry Res. 2020; 285:112711.