MicroRNAs in mental health: from biological underpinnings to potential therapies.
Psychiatric illnesses are disabling disorders with poorly understood underlying pathophysiologies. However, it is becoming increasingly evident that these illnesses result from disruptions across whole cellular networks rather than any particular monoamine system. Recent evidence continues to support the hypothesis that these illnesses arise from impairments in cellular plasticity cascades, which lead to aberrant information processing in the circuits that regulate mood, cognition, and neurovegetative functions (sleep, appetite, energy, etc.). As a result, many have begun to consider future therapies that would be capable of affecting global changes in cellular plasticity to restore appropriate synaptic function and neuronal connectivity. MicroRNAs (miRNAs) are non-coding RNAs that can repress the gene translation of hundreds of their targets and are therefore well-positioned to target a multitude of cellular mechanisms. Here, we review some properties of miRNAs and show they are altered by stress, glucocorticoids, mood stabilizers, and in a particular psychiatric disorder, schizophrenia. While this field is still in its infancy, we consider their potential for regulating behavioral phenotypes and targeting key predicted signaling cascades that are implicated in psychiatric illness. Clearly, considerable research is required to better determine any therapeutic potential of targeting miRNAs; however, these agents may provide the next generation of effective therapies for psychiatric illnesses.
Hunsberger
Joshua G
JG
Laboratory of Molecular Pathophysiology, National Institute of Mental Health, National Institutes of Health, 9000 Rockville Pike, Building 35, 1C912, Bethesda, MD 20892, USA. hunsbergerj@mail.nih.gov
Austin
Daniel R
DR
Chen
Guang
G
Manji
Husseini K
HK
D000818:Animals; D001519:Behavior / Q000502:physiology; D020022:Genetic Predisposition to Disease; D005938:Glucocorticoids / Q000378:metabolism; D006801:Humans; D001523:Mental Disorders / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D008603:Mental Health; D035683:MicroRNAs / Q000235:genetics / Q000627:therapeutic use; D010641:Phenotype; D013312:Stress, Physiological / Q000502:physiology; D013315:Stress, Psychological / Q000503:physiopathology
D005938:Glucocorticoids; D035683:MicroRNAs