Plasma circulating microRNAs and symptoms of depression: Results from a population-based study

Depression is a complex mental disorder with a multifactorial etiology. Recent research has highlighted the potential of microRNAs (miRNAs) as novel biomarkers and their involvement in the molecular pathways underlying depression; yet, these studies often focus on limited clinical samples and specific subsets of miRNAs. Here we aimed to explore plasma miRNA expression profiles associated with depressive symptoms in a population-based study of middle-aged and older adults.

We analyzed the levels of 591 circulating miRNAs well-expressed in plasma samples of 2,703 participants of the Rotterdam Study. The Center for Epidemiologic Studies Depression Scale was used to assess depressive symptoms in these participants. Negative-binomial regression models were employed to explore the relationship between individual miRNA levels and depressive symptoms, adjusting for potential confounders including age, sex, BMI, and other factors.

Our analysis suggests 38 circulating miRNAs to be potentially associated with depressive symptoms (P < 0.05). Although these miRNAs did not survive multiple testing correction, our subsequent in silico analysis of their target genes suggests involvement in neural and psychiatric pathways, as well as enrichment for associations with depressive symptoms based on previous genome-wide association studies.

This study proposes several circulating miRNAs that may be associated with depressive symptoms within the general population. Our follow-up analyses indicate that the miRNAs with the largest effect estimates were potentially involved in neurological and psychiatric processes, warranting further investigation into their potential role in the biological mechanisms of depression. These results provide preliminary insights and should be considered exploratory and hypothesis-generating, warranting validation in future studies with larger and independent cohorts.