Mood congruent psychotic symptoms and specific cognitive deficits in carriers of the novel schizophrenia risk variant at MIR-137

Cummings, Elizabeth; Donohoe, Gary; Hargreaves, April; Moore, Susan; Fahey, Ciara; Dinan, Timothy G.; McDonald, Colm; O’Callaghan, Eadbhard; O'Neill, F. Anthony; Waddington, John L.; Murphy, K. C.; Morris, Derek W.; Gill, Michael; Corvin, Aiden

doi:10.1016/j.neulet.2012.08.065

Cited by 63 publications

(52 citation statements)

References 18 publications

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“…Our study demonstrated a weak but significant association between the TT genotype and lower scores in digit sequencing for working memory in the Chinese Han population, which is similar to the results of Cummings et al [15], who showed that the polymorphism rs1625579 was also associated with cognitive deficits in schizophrenia, including working memory (assessed using the CANTAB Spatial Working Memory task) ( P < 0.0001). In addition, overlapping microdeletion of the miR-137 locus in the chromosomal region 1p21.3 has been identified in patients with intellectual disabilities [28].…”

Section: Discussionsupporting

confidence: 90%

Association of a miRNA-137 Polymorphism with Schizophrenia in a Southern Chinese Han Population

Yin

et al. 2014

BioMed Research International

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Both genome wide association study (GWAS) and biochemical studies of Caucasian populations indicate a robust association between the miR-137 genetic variant rs1625579 and schizophrenia, but inconsistent results have been reported. To assay the association between this variant and schizophrenia, we genotyped 611 schizophrenic patients from Southern Chinese Han population for the risk single nucleotide polymorphism (SNP) rs1625579 using the SNaPshot technique and compared the clinical profiles of different genotypes. Additionally, a meta-analysis was performed using the combined sample groups from five case-control publications and the present study. Both the genotype and allele distributions of the rs1625579 SNP were significantly different between patients and controls (P = 0.036 and 0.026, SNP). TT genotype carriers showed slightly lower Brief Assessment of Cognition in Schizophrenia- (BACS-) derived working memory performance than G carriers (15.58 ± 9.56 versus 19.71 ± 8.18, P = 0.045). In the meta-analysis, we observed a significant association between rs1625579 and schizophrenia under different genetic models (all P < 0.05). The results of our study and meta-analysis provide convincing evidence that rs1625579 is significantly associated with schizophrenia. Furthermore, the miR-137 polymorphism influences the working memory performance of schizophrenic patients in a Chinese Han population.

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Section: Discussionsupporting

confidence: 90%

Association of a miRNA-137 Polymorphism with Schizophrenia in a Southern Chinese Han Population

Yin

et al. 2014

BioMed Research International

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“…[75] strongly predicting an earlier age-at-onset of psychosis, reduced white matter integrity, and cognitive deficits in combination with higher severity of negative symptoms [84][85][86]. Moreover, two SNPs in the Dgcr8 and Dicer gene have been significantly associated with an altered schizophrenia risk in a Chinese schizophrenia patient cohort, suggesting that the specific genetic variants in miRNA machinery genes may affect the susceptibility to the disease [87].…”

Section: Mirnamentioning

confidence: 99%

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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“…Analysis of symptom severity scores was based on a principal components analysis with varimax rotation of OPCRIT scores, yielding a fivefactor solution of positive, negative, disorganised, manic, and depressive symptoms, as typically described and as previously reported for this sample (Cummings et al, 2013). Furthermore, as all neuropsychological measures were significantly associated with the GAF, and in order to simplify further analyses, we created a composite score of neurocognition using extracted regression values from an un-rotated principal components analysis.…”

Section: Assessment Of Neuropsychological Function and Social Cognitionmentioning

confidence: 99%

Social dysfunction in schizophrenia: An investigation of the GAF scale's sensitivity to deficits in social cognition

Robertson

Hargreaves

Kelleher

et al. 2013

Schizophrenia Research

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Background: Schizophrenia is accompanied by significant impairment in psychosocial functioning, which is only partially explained by clinical symptom severity. Recently, these impairments have been strongly associated with deficits in neurocognition and social cognition. Although the Global Assessment of Function (GAF) scale remains the most widely used measure of psychosocial function in clinical practice, it is unclear whether this instrument is sensitive to changes in cognition, or merely provides a snapshot of symptom severity. To investigate this, we assessed whether variation in GAF score was explained by performance on measures of neurocognitive and social cognition, particularly after variation associated with symptom severity had been accounted for. Methods: 216 patients with schizophrenia were assessed using the GAF scale, two theory of mind tasks (the 'Hinting' task and 'Reading the Eyes in the Mind' task), and a neuropsychological battery sensitive to the areas of deficit typically seen in schizophrenia -IQ, episodic memory, working memory and attentional control. Results: Using linear regression analysis, symptom severity explained 24% of the variance in GAF scores (F(3, 188) = 21.14, p b .001). While neuropsychological performance explained a further 4.7% of variation (r 2 change = .047, F change (1, 187) = 12.63, p b .001), social cognition did not explain any further variance in functioning (r 2 change =.006, F change (1, 186)=1.63, p=.20). Conclusion: These data indicate that GAF scores are primarily sensitive to variation in clinical symptoms severity and not at all sensitive to variation in social cognition, an important determinant of real world outcome. Doing so highlights the need to supplement the measurement of psychosocial function using the GAF in clinical practice with functional measures that are more sensitive to deficits in social cognition.

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Mood congruent psychotic symptoms and specific cognitive deficits in carriers of the novel schizophrenia risk variant at MIR-137

Cited by 63 publications

References 18 publications

Association of a miRNA-137 Polymorphism with Schizophrenia in a Southern Chinese Han Population

Association of a miRNA-137 Polymorphism with Schizophrenia in a Southern Chinese Han Population

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

Social dysfunction in schizophrenia: An investigation of the GAF scale's sensitivity to deficits in social cognition

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