Impact of a microRNA MIR137 Susceptibility Variant on Brain Function in People at High Genetic Risk of Schizophrenia or Bipolar Disorder

Whalley, Heather C.; Papmeyer, Martina; Romaniuk, Liana; Sprooten, Emma; Johnstone, Eve C.; Hall, Jérémy; Lawrie, Stephen M.; Evans, Kathryn; Blumberg, Hilary P.; Sussmann, Jessika E.; McIntosh, Andrew M.

doi:10.1038/npp.2012.137

Cited by 81 publications

(73 citation statements)

References 67 publications

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“…The analysis of the relationship between rs1625579 genotypes and miR-137 expression in the postmortem DLPFC revealed a significantly lower miR-137 expression level in the homozygous TT subjects compared to TG and GG subjects in the control group [82]. Moreover, homozygous TT individuals at high genetic risk for schizophrenia exhibited a lower activation in the posterior right medial frontal gyrus compared to healthy controls after a sentence completion task that differentiates individuals with schizophrenia and their relatives from controls [83]. Further studies demonstrated that the risk variant rs1625579 might substantially influence phenotypic variability in schizophrenia, with the miR-137 risk genotype Table 1 The miRNA abnormalities in schizophrenia and bipolar disorder patient brain tissues…”

Section: Mirnas In Schizophrenia: Results From Human Studiesmentioning

confidence: 98%

MicroRNAs in Schizophrenia: Implications for Synaptic Plasticity and Dopamine–Glutamate Interaction at the Postsynaptic Density. New Avenues for Antipsychotic Treatment Under a Theranostic Perspective

et al. 2014

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Despite dopamine-glutamate aberrant interaction that has long been considered a relevant landmark of psychosis pathophysiology, several aspects of these two neurotransmitters reciprocal interaction remain to be defined. The emerging role of postsynaptic density (PSD) proteins at glutamate synapse as a molecular "lego" making a functional hub where different signals converge may add a new piece of information to understand how dopamine-glutamate interaction may work with regard to schizophrenia pathophysiology and treatment. More recently, compelling evidence suggests a relevant role for microRNA (miRNA) as a new class of dopamine and glutamate modulators with regulatory functions in the reciprocal interaction of these two neurotransmitters. Here, we aimed at addressing the following issues: (i) Do miRNAs have a role in schizophrenia pathophysiology in the context of dopamine-glutamate aberrant interaction? (ii) If miRNAs are relevant for dopamine-glutamate interaction, at what level this modulation takes place? (iii) Finally, will this knowledge open the door to innovative diagnostic and therapeutic tools? The biogenesis of miRNAs and their role in synaptic plasticity with relevance to schizophrenia will be considered in the context of dopamine-glutamate interaction, with special focus on miRNA interaction with PSD elements. From this framework, implications both for biomarkers identification and potential innovative interventions will be considered.

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Section: Mirnas In Schizophrenia: Results From Human Studiesmentioning

confidence: 98%

MicroRNAs in Schizophrenia: Implications for Synaptic Plasticity and Dopamine–Glutamate Interaction at the Postsynaptic Density. New Avenues for Antipsychotic Treatment Under a Theranostic Perspective

et al. 2014

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“…and qRT-PCR validation and discovered just one miRNA, miR29c, to be upregulated. The SNP rs1625579, which affects miR-137 in SZ, was also found to be functionally associated with individuals at risk of BD (45).…”

Section: Bdmentioning

confidence: 96%

MicroRNA and Posttranscriptional Dysregulation in Psychiatry

Geaghan

Cairns

2015

Biological Psychiatry

164

122

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Psychiatric syndromes, including schizophrenia, mood disorders, and autism spectrum disorders, are characterized by a complex range of symptoms, including psychosis, depression, mania, and cognitive deficits. Although the mechanisms driving pathophysiology are complex and remain largely unknown, advances in the understanding of gene association and gene networks are providing significant clues to their etiology. In recent years, small noncoding RNA molecules known as microRNA (miRNA) have emerged as potential players in the pathophysiology of mental illness. These small RNAs regulate hundreds of target transcripts by modifying their stability and translation on a broad scale, influencing entire gene networks in the process. There is evidence to suggest that numerous miRNAs are dysregulated in postmortem neuropathology of neuropsychiatric disorders, and there is strong genetic support for association of miRNA genes and their targets with these conditions. This review presents the accumulated evidence linking miRNA dysregulation and dysfunction with schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorders and the potential of miRNAs as biomarkers or therapeutics for these disorders. We further assess the functional roles of some outstanding miRNAs associated with these conditions and how they may be influencing the development of psychiatric symptoms.

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“…Mega-analysis has advantages over meta-analysis in that datasets can be combined to enhance statistical power, permitting examination of hypotheses that cannot be tested within single studies. This approach has been used to combine datasets in areas such as genetics (Whalley et al, 2012), functional neuroimaging (Hallahan et al, 2011), and psychiatric treatment (de Maat et al, 2008;Thase et al, 1997). The current study used the combined dataset to address three novel goals: (1) to test the direct versus indirect (mediated by autobiographical belief) effects of suggestion on suggestion-related preferences and behavior intention; (2) to examine the impact of the development (x), which in turn influence behavior (y).…”

Section: Introductionmentioning

confidence: 99%