MicroRNAs as a target for novel antipsychotics: a systematic review of an emerging field.

The psychotic disorders of schizophrenia and bipolar affective disorder are among the most disabling of all medical conditions. Current drugs used to treat psychosis largely target monoamine receptors. Here we explore the possibility of developing new antipsychotics by targeting specific microRNAs (miRNAs). These are single-stranded RNA molecules, 21-23 nt in length that are not translated into proteins and function as regulatory molecules. A keyword search was performed using Medline, the ISI Web of Knowledge and Scopus for papers published up to June 2009. The search shows that to date studies of miRNAs have been far more abundant in schizophrenia than in bipolar affective disorder and the view that non-protein-coding genes have an important regulatory role with implications for the genetic liability to psychosis is gaining greater acceptance. The most promising miRNAs so far identified include miR-181, miR-346 and miR-195 in schizophrenia and miR-34a and miR-144 in bipolar disorder. It has been argued that miR-219 may be involved in both disorders. miRNAs offer an exciting potential for developing new antipsychotics, although research in the field is at an early stage. It will require a considerable advance in smart technologies to deliver either mimics or antagomirs to the appropriate site of action, but the development of selective small conventional molecules may negate this requirement.