The diagnostic utility of miRNA and elucidation of pathological mechanisms in major depressive disorder.

Aims: Our study aims to explore how miRNAs can elucidate the molecular mechanisms of major depressive disorder (MDD) by comparing the miRNA levels in the blood serum of patients with depression and healthy individuals. It also explores the potential of miRNAs to differentiate between depressed patients and healthy controls.

Methods: 60 healthy controls (n = 45 females) were matched to 60 depressed patients (n = 10 unmedicated) for age (±7), sex, ethnicity, and years of education. Depression severity was measured using the Hamilton Depression Rating Scale, and venous blood was collected using PAXgene Blood RNA tubes for miRNA profiling. To further identify the depression-related biological pathways that are influenced by differentially expressed miRNAs, networks were constructed using QIAGEN Ingenuity Pathway Analysis. Receiver operating characteristic (ROC) analyses were also conducted to examine the discriminative ability of miRNAs to distinguish between depressed and healthy individuals.

Results: Six miRNAs (miR-542-3p, miR-181b-3p, miR-190a-5p, miR-33a-3p, miR-3690 and miR-6895-3p) showed to be considerably down-regulated in unmedicated depressed patients relative to healthy controls. miR-542-3p, in particular, also has experimentally verified mRNA targets that are predicted to be associated with MDD. ROC analyses found that a panel combining miR-542-3p, miR-181b-3p and miR-3690 produced an area under the curve value of 0.67 in distinguishing between depressed and healthy individuals.

Conclusions: miRNAs - most notably, miR-542-3p, miR-181b-3p and miR-3690 - may be biomarkers with targets that are implicated in the pathophysiology of depression. They could also be used to distinguish between depressed and healthy individuals with reasonable accuracy.