Abstract:
: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.
journal_name
Mol Psychiatryjournal_title
Molecular psychiatryauthors
O'Connor RM,Dinan TG,Cryan JFdoi
10.1038/mp.2011.162subject
Has Abstractpub_date
2012-04-01 00:00:00pages
359-76issue
4eissn
1359-4184issn
1476-5578pii
mp2011162journal_volume
17pub_type
杂志文章,评审abstract::Post-traumatic stress disorder (PTSD) impacts many veterans and active duty soldiers, but diagnosis can be problematic due to biases in self-disclosure of symptoms, stigma within military populations, and limitations identifying those at risk. Prior studies suggest that PTSD may be a systemic illness, affecting not ju...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-019-0496-z
更新日期:2020-12-01 00:00:00
abstract::Endocannabinoids and their attending cannabinoid type 1 (CB1) receptor have been implicated in animal models of post-traumatic stress disorder (PTSD). However, their specific role has not been studied in people with PTSD. Herein, we present an in vivo imaging study using positron emission tomography (PET) and the CB1-...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2013.61
更新日期:2013-09-01 00:00:00
abstract::Post-traumatic stress disorder (PTSD) is associated with elevated risk for a variety of age-related diseases and neurodegeneration. In this paper, we review evidence relevant to the hypothesis that chronic PTSD constitutes a form of persistent life stress that potentiates oxidative stress (OXS) and accelerates cellula...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:10.1038/mp.2014.111
更新日期:2014-11-01 00:00:00
abstract::Emerging evidence suggests that psychiatric disorders are associated with disturbances in structural brain networks. Little is known, however, about brain networks in those at high risk (HR) of bipolar disorder (BD), with such disturbances carrying substantial predictive and etiological value. Whole-brain tractography...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2016.216
更新日期:2018-02-01 00:00:00
abstract::The goal of this study is to investigate the familial transmission of the spectrum of bipolar disorder in a nonclinical sample of probands with a broad range of manifestations of mood disorders. The sample included a total of 447 probands recruited from a clinically enriched community screening and their 2082 adult li...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2013.116
更新日期:2014-02-01 00:00:00
abstract::Circular RNAs (circRNAs), highly expressed in the central nervous system, are involved in various regulatory processes and implicated in some pathophysiology. However, the potential role of circRNAs in psychiatric diseases, particularly major depressive disorder (MDD), remains largely unknown. Here, we demonstrated th...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-018-0285-0
更新日期:2020-06-01 00:00:00
abstract::The methionine-folate cycle-dependent one-carbon metabolism is implicated in the pathophysiology of schizophrenia. Since schizophrenia is a developmental disorder, we examined the effects that perturbation of the one-carbon metabolism during gestation has on mice progeny. Pregnant mice were administered methionine equ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2017.164
更新日期:2018-02-01 00:00:00
abstract::Dietary intake of methyl donors, such as folic acid and methionine, shows considerable intra-individual variation in human populations. While it is recognized that maternal departures from the optimum of dietary methyl donor intake can increase the risk for mental health issues and neurological disorders in offspring,...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2017.53
更新日期:2018-05-01 00:00:00
abstract::Tonically active cholinergic interneurons (TANs) from the nucleus accumbens (NAc) are centrally involved in reward behavior. TANs express a vesicular glutamate transporter referred to as VGLUT3 and thus use both acetylcholine and glutamate as neurotransmitters. The respective roles of each transmitter in the regulatio...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2015.104
更新日期:2015-11-01 00:00:00
abstract::Niemann-Pick disease type A (NPA) is a rare lysosomal storage disorder characterized by severe neurological alterations that leads to death in childhood. Loss-of-function mutations in the acid sphingomyelinase (ASM) gene cause NPA, and result in the accumulation of sphingomyelin (SM) in lysosomes and plasma membrane o...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2016.148
更新日期:2017-05-01 00:00:00
abstract::Psychiatric diseases have a strong heritable component known to not be restricted to DNA sequence-based genetic inheritance alone but to also involve epigenetic factors in germ cells. Initial evidence suggested that sperm RNA is causally linked to the transmission of symptoms induced by traumatic experiences. Here, we...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-018-0271-6
更新日期:2020-09-01 00:00:00
abstract::Maternal anxiety during pregnancy is associated with adverse foetal, neonatal, and child outcomes, but biological mechanisms remain unclear. Altered foetal DNA methylation (DNAm) has been proposed as a potential underlying mechanism. In the current study, we performed a meta-analysis to examine the associations betwee...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-020-00976-0
更新日期:2021-01-07 00:00:00
abstract::Opioids, such as morphine, are clinic analgesics which induce euphoria. Morphine exposure modifies the excitability and functional interactions between neurons, while the underlying cellular and molecular mechanisms, especially how morphine assembles heterogeneous interneurons (INs) in prelimbic cortex (PrL) to mediat...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-019-0480-7
更新日期:2019-08-14 00:00:00
abstract::Genomic risk profile scores (GRPSs) have been shown to predict case-control status of schizophrenia (SCZ), albeit with varying sensitivity and specificity. The extent to which this variability in prediction accuracy is related to differences in sampling strategies is unknown. Danish population-based registers and Neon...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2015.130
更新日期:2016-07-01 00:00:00
abstract::Bipolar disorder (BD) is a progressive psychiatric disorder with more than 3% prevalence worldwide. Affected individuals experience recurrent episodes of depression and mania, disrupting normal life and increasing the risk of suicide greatly. The complexity and genetic heterogeneity of psychiatric disorders have chall...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2016.260
更新日期:2018-06-01 00:00:00
abstract::Linkage disequilibrium (LD) mapping was used to follow up reports of linkage between reading disability (RD) and an 18 cM region of chromosome 6p21.3-22. Using a two-stage approach, we tested for association between RD and 22 microsatellite markers in two independent samples of 101 (Stage 1) and 77 (Stage 2) parent/pr...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001216
更新日期:2003-02-01 00:00:00
abstract::Current antidepressants act principally by blocking monoamine reuptake by high-affinity transporters in the brain. However, these antidepressants show important shortcomings such as slow action onset and limited efficacy in nearly a third of patients with major depression disorder. Here, we report the development of a...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-019-0548-4
更新日期:2020-06-01 00:00:00
abstract::Long-term weight-restored patients with anorexia nervosa (AN) have lower norepinephrine levels than controls. Since this may reflect altered reuptake by the norepinephrine transporter (NET), we hypothesised that the NET gene was involved in the genetic component of AN. PCR-amplification of an AAGG repeat island (AAGG1...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001080
更新日期:2002-01-01 00:00:00
abstract::Peripheral blood brain-derived neurotrophic factor (BDNF) has been proposed as a potential biomarker related to disease activity and neuroprogression in bipolar disorder, speculated to mirror alterations in brain expression of BDNF. The research area is rapidly evolving; however, recent investigations have yielded con...
journal_title:Molecular psychiatry
pub_type: 杂志文章,meta分析,评审
doi:10.1038/mp.2015.54
更新日期:2016-02-01 00:00:00
abstract::Low dietary folate intake has been implicated as a risk factor for depression. However, observational epidemiological studies are plagued by problems of confounding, reverse causality and measurement error. A common polymorphism (C677T) in MTHFR is associated with methyltetrahydrofolate reductase (MTHFR) activity and ...
journal_title:Molecular psychiatry
pub_type: 杂志文章,meta分析,评审
doi:10.1038/sj.mp.4001790
更新日期:2006-04-01 00:00:00
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journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-019-0635-6
更新日期:2020-01-03 00:00:00
abstract::Identifying genes for bipolar mood disorders through classic genetics has proven difficult. Here, we present a comprehensive convergent approach that translationally integrates brain gene expression data from a relevant pharmacogenomic mouse model (involving treatments with a stimulant--methamphetamine, and a mood sta...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001547
更新日期:2004-11-01 00:00:00
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journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4000902
更新日期:2001-11-01 00:00:00
abstract::Serotonin (5-HT) neurons project from the raphe nuclei throughout the brain where they act to maintain homeostasis. Here, we study 5-HT inputs into the bed nucleus of the stria terminalis (BNST), a major subdivision of the extended amygdala that has been proposed to regulate responses to anxiogenic environments in hum...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2017.165
更新日期:2018-10-01 00:00:00
abstract::Autism spectrum disorder (ASD) is characterized by neurocognitive dysfunctions, such as impaired social interaction and language learning. Gene-environment interactions have a pivotal role in ASD pathogenesis. Nuclear receptor corepressors (NCORs) are transcription co-regulators physically associated with histone deac...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:10.1038/s41380-020-0667-y
更新日期:2020-10-01 00:00:00
abstract::The literature on GWAS (genome-wide association studies) data suggests that very large sample sizes (for example, 50,000 cases and 50,000 controls) may be required to detect significant associations of genomic regions for complex disorders such as Alzheimer's disease (AD). Because of the challenges of obtaining such l...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2012.81
更新日期:2013-05-01 00:00:00
abstract::We assessed the ability of lithium to reduce neurodegeneration and to stimulate cell proliferation in a rat model of Huntington's disease in which quinolinic acid (QA) was unilaterally infused into the striatum. LiCl (0.5-3.0 mEq/kg) was injected subcutaneously 24 h before and 1 h after QA infusion. At 7 days after QA...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001463
更新日期:2004-04-01 00:00:00
abstract::Among the most consistent results of studies of post-mortem brain tissue from schizophrenia patients (SZP) is the finding that in this disease, several genes expressed by GABAergic neurons are downregulated. This downregulation may be caused by hypermethylation of the relevant promoters in affected neurons. Indeed, in...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001954
更新日期:2007-04-01 00:00:00
abstract::Genomewide association studies have found significant genetic correlations among many neuropsychiatric disorders. In contrast, we know much less about the degree to which structural brain alterations are similar among disorders and, if so, the degree to which such similarities have a genetic etiology. From the Enhanci...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-020-01002-z
更新日期:2021-01-17 00:00:00
abstract::Large numbers of single nucleotide polymorphisms (SNPs) are being identified by several laboratories for the purpose of developing dense genetic maps. Single-strand conformation polymorphism (SSCP) analysis has been widely used as a method for detecting novel sequence variations in PCR products. Differences in migrati...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4000564
更新日期:1999-07-01 00:00:00