The use of miRNAs as a peripheral biomarker in MDD is gaining momentum. Belzeaux et al examined miRNA expression profiles in peripheral blood mononuclear cells (PBMCs) collected from

16 severe MDD patients and 13 matched controls at baseline, and 2 and 8 weeks after AC220 mw treatment (Table I). 179 A comparison of miRNA expression between MDD patients and controls at baseline and at 8 weeks showed a similar Inhibitors,research,lifescience,medical number of dysregulated miRNAs (14 miRNAs, with 9 miRNAs upregulated and 5 downregulated). miRNAs that showed changes between MDD and controls at base line included: has-miR-107, miR-133a, miR-148a, miR-200c, miR-381, miR-425-3p, miR-494, miR-517b, miR-579, miR-589, miR-636, miR-652, miR-941, and miR-1 243. Only two miRNAs showed stable overexpression in MDD patients during the 8-week follow-up compared with controls (miR-941 and miR-589). They also identified miRNAs exhibiting significant variations of expression among patients Inhibitors,research,lifescience,medical with clinical improvement (7 upregulated and

1 downregulated). Fourteen dysregulated miRNAs had putative mRNA targets Inhibitors,research,lifescience,medical that were differentially expressed in MDD, suggesting that a common RNA regulatory network functions in MDD. These results suggest the potential utility of miRNA signatures as markers of major depressive episode evolution. Bocchio-Chiavetto et al conducted a whole-miRNA ome quantitative analysis in the blood of 10 MDD subjects after 12 weeks of treatment with escitalopram (Table I).180 They Inhibitors,research,lifescience,medical found that 30 miRNAs were differentially expressed after the escitalopram treatment: 28 miRNAs were upregulated, and two miRNAs were downregulated. Thirteen (let-7d, let-7e, miR-26a, miR-26b, miR-34c-5p, miR-103, miR-128, miR-132, miR-183, miR-192, miR-335, Inhibitors,research,lifescience,medical miR-494, and miR-22) play a role in neural plasticity and stress response and in the pathogenetic mechanisms of several neuropsychiatric

diseases. miR-132 exerts critical functions in the biological circuits implicated in neurogenesis and synaptic plasticity, stimulating axonal and dendritic outgrowth in different brain areas.181 This miRNA, together with miR-26a, miR-26b, and miR-183, widely contributes to PDK4 the action of the neurotrophin BDNF in the brain.103,134,182,183 miR-132, miR-26a, miR-26b, miR-183, let-7d, let-7e, miR-26b, miR-103, miR-128, miR-494, and miR-22 have been reported to play a role in the pathogenesis of psychiatric disorders and in the mechanism of action of antipsychotic drugs and mood stabilizers. Moreover, postmortem studies on the brains of bipolar disorder patients showed increased levels of miR-22* in the prefrontal cortex.184 On the other hand, miR-494 and miR-335 are downregulated in the prefrontal cortex of MDD patients.