Plasma circRNAs as potential biomarkers to assist in the diagnosis of postpartum depression

Background: This research sought to examine alterations in plasma circular RNA (circRNA) expression in women with postpartum depression (PPD), assessing its potential utility as an auxiliary diagnostic biomarker for this condition. 

Methods: Women examined at 42 days postpartum were recruited between June 2024 and December 2024, during which plasma samples and relevant data were collected. A discovery cohort was established, consisting of 3 women with PPD and 3 control participants. This was followed by a validation cohort of 50 women with PPD and 50 controls, identified using the Structured Clinical Interview. The discovery cohort underwent plasma circRNA microarray analysis, whereas the validation cohort used reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to quantify candidate circRNAs and five circRNAs previously associated with major depressive disorder (MDD).

Results: Plasma levels of circRNA derived from the Interferon Gamma Receptor 2 gene (circIFNGR2), circRNA derived from the ATP-Binding Cassette Subfamily C Member 5 gene (circABCC5), circRNA derived from the Activating Transcription Factor 7 Interacting Protein gene (circATF7IP) were significantly upregulated in the PPD group, whereas circRNA derived from the Dystrophia Myotonica Protein Kinase gene (circDYM) was significantly downregulated (p < 0.05). The area under the curve (AUC) of the four circRNAs, circIFNGR2, circABCC5, circDYM, and circATF7IP, was 0.62 (sensitivity 28%, specificity 96%), 0.64 (sensitivity 36%, specificity 96%), 0.69 (sensitivity 54%, specificity 84%), and 0.65 (sensitivity 62%, specificity 72%), respectively. The joint AUC of circIFNGR2, circABCC5, circDYM, and circATF7IP was 0.80 (sensitivity 78%, specificity 70%). After adjustment for covariates, circIFNGR2, circABCC5, and circATF7IP remained independent predictive factors. 

Conclusions: Changes in the levels of circIFNGR2, circABCC5 identified by microarray analysis, as well as circDYM, and circATF7IP associated with MDD, were associated with the occurrence of PPD. These findings support the potential utility of circRNAs as adjunct diagnostic biomarkers for PPD and offer valuable insights into the molecular mechanisms underlying the disorder.