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MicroRNAs in mental health: from biological underpinnings to potential therapies.

ABSTRACT: 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.

SUBMITTER: Hunsberger JG

PROVIDER: S-EPMC2754593 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

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MicroRNAs in mental health: from biological underpinnings to potential therapies.

Hunsberger Joshua G JG Austin Daniel R DR Chen Guang G Manji Husseini K HK

Neuromolecular medicine 20090620 3

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 neurovege ...[more]

PMID: 19544012

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Project description:BACKGROUND:Preeclampsia remains a significant danger to both mother and child and current prevention and treatment management strategies are limited. The objective of this systematic review was to investigate the current literature on evidence for the use of the regenerative capacity of mesenchymal stem cell (MSC) therapy, the anticoagulant activity of antithrombin (AT), or the free radical scavenging activity of alpha-1-microglobulin (A1M) as potential novel treatments for severe preeclampsia and Hemolysis, Elevated Liver enzymes, Low Platelet count (HELLP). METHOD:We conducted a systematic review of potential biological therapies for preeclampsia. We screened MEDLINE and Embase from inception through May 2017 for studies using AT, A1M or MSCs as potential treatments for preeclampsia and/or HELLP. A meta-analysis was performed to pool data from randomized control trials (RCTs) with homogenous outcomes using the inverse variance method. The Newcastle-Ottawa Scale, the Cochrane risk of bias tool for RCTs, and SYRCLE's risk of bias tool for animal studies were used to investigate potential bias of studies. RESULTS:The literature search retrieved a total of 1015 articles, however, only 17 studies met the selection criteria: AT (n = 9, 8 human and 1 animal); A1M (n = 4, 3 animal and 1 ex-vivo); and, MSCs (n = 4, 3 animal and 1 ex-vivo). A meta-analysis of AT therapy versus placebo and a meta-analysis for AT therapy with heparin versus heparin alone did not show significant differences between study groups. Animal and ex-vivo studies demonstrated significant benefits in relevant outcomes for A1M and MSCs versus control treatments. Most RCT studies were rated as having a low risk of bias across categories with some studies showing an unclear risk of bias in some categories. The two cohort studies both received a total of four out of nine stars (a rating of "poor" quality). Most animal studies had an unclear risk of bias across most categories, with some studies having a low risk of bias in some categories. CONCLUSIONS:The findings of this review are strengthened by rigorous systematic search and review of the literature. Results of our meta-analyses do not currently warrant further exploration of AT as a treatment of preeclampsia in human trials. Results of animal and ex-vivo studies of A1M and MSCs were encouraging and supportive of initiating human investigations.

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MicroRNAs in mental health: from biological underpinnings to potential therapies.

Publications

MicroRNAs in mental health: from biological underpinnings to potential therapies.

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