Little things on which happiness depends: microRNAs as novel therapeutic targets for the treatment of anxiety and depression

R M O'Connor, T G Dinan, J F Cryan

Anxiety and depression are devastating mental illnesses that are a significant public health concern. Selective serotonin-reuptake inhibitors are the first-line treatment strategy for these disorders, which despite being a significant advantage over older treatments, are hampered by a limited efficacy in a significant subset of patients, delayed onset of action and side effects that affect compliance. Thus, there is much impetus to develop novel therapeutic strategies. However, this goal can only be rationally realised with a better understanding of the molecular pathophysiology of these disorders. MicroRNAs (miRNAs) are a newly discovered class of gene-expression regulators that may represent a novel class of therapeutic targets to treat a variety of disorders including psychiatric diseases. miRNAs are heavily involved in regulating many physiological processes including those fundamental to the functioning of the central nervous system. Evidence collected to date has already demonstrated that miRNA-expression levels are altered in patients suffering from depression and anxiety and in pre-clinical models of psychological stress. Furthermore, increasing evidence suggests that psychoactive agents including antidepressants and mood stabilisers utilise miRNAs as downstream effectors. Altering miRNA levels has been shown to alter behaviour in a therapeutically desirable manner in pre-clinical models. This review aims to outline the evidence collected to date demonstrating miRNAs role in anxiety and depression, the potential advantages of targeting these small RNA molecules as well as some of the hurdles that will have to be overcome to fully exploit their therapeutic potential.