Major depression (MD) and bipolar disorder (BD) are severe and potentially life-threating mood disorders whose etiology is to date not completely understood. MicroRNAs (miRNAs) are small non-coding RNAs that regulate protein synthesis post-transcriptionally by base-pairing to target gene mRNAs. Growing evidence indicated that miRNAs might play a key role in the pathogenesis of neuropsychiatric disorders and in the action of psychotropic drugs. On these bases, in this study we evaluated the expression levels of 1733 mature miRNAs annotated in miRBase v.17, through a microarray technique, in the blood of 20 MD and 20 BD patients and 20 healthy controls, in order to identify putative miRNA signatures associated with mood disorders. We found that 5 miRNAs (hsa-let-7a-5p, hsa-let-7d-5p, hsa-let-7f-5p, hsa-miR-24-3p and hsa-miR-425-3p) were specifically altered in MD patients and 5 (hsa-miR-140-3p, hsa-miR-30d-5p, hsa-miR-330-5p, hsa-miR-378a-5p and hsa-miR-21-3p) in BD patients, whereas 2 miRNAs (hsa-miR-330-3p and hsa-miR-345-5p) were dysregulated in both the diseases. The bioinformatic prediction of the genes targeted by the altered miRNAs revealed the possible involvement of neural pathways relevant for psychiatric disorders. In conclusion, the observed results indicate a dysregulation of miRNA blood expression in mood disorders and could indicate new avenues for a better understanding of their pathogenetic mechanisms. The identified alterations may represent potential peripheral biomarkers to be complemented with other clinical and biological features for the improvement of diagnostic accuracy.

MicroRNAs (miRNAs) are small non-coding RNAs (20-22 nucleotides) playing a major role in post-transcriptional regulation of gene expression. miRNAs are predicted to regulate more than 50% of all the protein-coding genes. Increasing evidence indicates that they may play key roles in the biological pathways that regulate neurogenesis and synaptic plasticity, as well as in neurotransmitter homeostasis in the adult brain. In this article we review recent studies suggesting that miRNAs may be involved in the pathophysiology of neuropsychiatric disorders and in the action of CNS drugs, in particular by analyzing the contribution of genomic studies in patients' peripheral tissues. Alterations in miRNA expression have been observed in schizophrenia, bipolar disorder, major depression, Parkinson's disease, Alzheimer's disease and other neuropsychiatric conditions. In particular, intriguing findings concern the identification of disease-associated miRNA signatures in patients' peripheral tissues, or modifications in miRNA profiles induced by drug treatments. Furthermore, genetic variations in miRNA sequences and miRNA-related genes have been described in neuropsychiatric diseases. Overall, though still at a preliminary stage, several lines of evidence indicate an involvement of miRNAs in both the pathophysiology and pharmacotherapy of neuropsychiatric disorders. In this regard, the data obtained in patients' peripheral tissues may provide further insights into the etiopathogenesis of several brain diseases and contribute to identify new biomarkers for diagnostic assessment improvement and treatment personalization.

Background Anxiety disorders exhibit remarkably high rates of comorbidity with major depressive disorder (MDD). Mood and anxiety disorders are considered stress-related diseases. Genetic variations in the co-chaperone FK506-binding protein 51, FKBP5, which modulates the function of glucocorticoid receptors, have been associated with an increased risk for the development of posttraumatic stress disorder, but data regarding its role in MDD are controversial. The aims of this study were to clarify the role of the FKBP5 gene in depression and anxiety disorders through a case–control study and an association study with personality traits using the Temperament and Character Inventory (TCI) in healthy subjects. Methods Six hundred fifty-seven MDD patients, with or without an anxiety disorder in comorbidity, and 462 healthy volunteers were enrolled in the study. Two hundred fifty-six controls agreed to fill out the TCI. Results The results showed that the T allele of rs1360780 was more frequent among the patients affected by MDD with a comorbidity of anxiety disorders, compared to those without (P < .001). Among the controls, we found that the T allele more often exhibited personality traits associated with an increased vulnerability to anxiety. Conclusions These results support the hypothesis that allelic variants of FKBP5 are a risk factor for anxiety disorders. The identification of genetic variants involved in anxiety may have implications for the optimization of therapeutic interventions.