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

Abstract Background: This research sought to examine alterations in plasma circular RNA (circRNA) expression in women with postpartum depressive disorder (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 controls. This was followed by a validation cohort of 50 women with PPD and 50 controls, who were identified using the Structured Clinical Interview. The discovery cohort underwent plasma circRNA microarray analysis, while the validation cohort used Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) to quantify candidate circRNAs, additionally including five circRNAs associated with major depressive disorder (MDD). Results: Plasma levels of circIFNGR2, circABCC5, and circATF7IP were significantly up-regulated in the PPD group, and circDYM were significantly down-regulated (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%]. Adjusting for covariates reveals that circIFNGR2, circABCC5, and circDYM were relatively independent predictive factors. Conclusion: Changes in the levels of circIFNGR2, circABCC5 (microarray-related), circDYM, and circATF7IP (MDD-related) are associated with the occurrence of PPD. Our results support the potential utility of circRNAs as adjunct diagnostic biomarkers for PPD and offer valuable insights into the molecular underpinnings of the disorder.