MIR137HG risk variant rs1625579 genotype is related to corpus callosum volume in schizophrenia

Patel, Vandana B.; Kelly, Sinéad; Wright, Carrie; Gupta, Cota Navin; Vasquez, Alejandro Arias; Perrone‐Bizzozero, Nora I.; Ehrlich, Stefan; Wang, Lei; Bustillo, Juan; Morris, Derek W.; Corvin, Aiden; Cannon, Dara M.; McDonald, Colm; Donohoe, Gary; Calhoun, Vince D.; Turner, Jessica A.

doi:10.1016/j.neulet.2015.06.039

Cited by 21 publications

(21 citation statements)

References 36 publications

(42 reference statements)

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“…When traumatic childhood attachment experiences remain unresolved it may account for reduced white matter integrity of the splenium, but abnormalities of the genu and body of the corpus callosum may be the consequence of a general vulnerability for psychopathology that might be a result of genetic influences [60] or prenatal stress [61]. Our findings indicated that the smaller FA values in the genu and body were due to increases in AD, RD, and MD.…”

Section: Accepted Manuscriptmentioning

confidence: 65%

General psychopathology factor and unresolved-disorganized attachment uniquely correlated to white matter integrity using diffusion tensor imaging

Riem

Hoof

Garrett

et al. 2019

Behavioural Brain Research

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HIGHLIGHTS Recent research has identified a general psychopathology factor (GPF)  GPF and Unresolved trauma may be uniquely related to white matter integrity (WMI)  Unresolved trauma is uniquely associated with reduced WMI in the splenium  GPF is uniquely related to reduced WMI in the genu and body of the corpus callosum ABSTRACT Background: A dimensional approach of psychopathology focuses on features and risk factors that are shared across diagnoses. In support for this dimensional approach, studies point to a general psychopathology factor (GPF) associated with risk for multiple psychiatric disorders. It is, however, unknown how GPF relates to white matter integrity (WMI). In the current diffusion tensor imaging (DTI) study, we examined how GPF relates to abnormalities in a skeleton representation of white matter tracts, taking into account a trans-diagnostic risk factor:unresolved-disorganized attachment (Ud) resulting from loss or trauma.Methods: Unique associations between GPF, Ud, and WMI were examined in a combined sample of adolescents (N=63) with childhood sexual abuse-related posttraumatic stress disorder (N = 18), anxiety and depressive disorders (N=26) and without psychiatric disorder (N=19).WMI was measured using DTI. Ud was measured using the Adult Attachment Interview. We controlled for puberty stage, gender, age, and IQ.Results: Controlling for GPF, Ud was associated with reduced fractional anisotropy (FA) in the splenium and inferior fronto-occipital fasciculus (IFOF). Controlling for Ud, GPF was associated with reduced FA in the genu and body of the corpus callosum. Conclusions:Decreasing WMI in the genu and body with increasing psychopathology across diagnoses suggests demyelinization in these areas and may underlie comorbidity and presence of symptoms that transcend psychopathological diagnoses. In contrast, trauma-related WMI reductions in the splenium and IFOF may account for heterogeneity within diagnostic categories as a function of childhood trauma. These findings support the importance of a dimensional approach in addition to traditional diagnostic classifications in clinical research and practice.

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Section: Accepted Manuscriptmentioning

confidence: 65%

General psychopathology factor and unresolved-disorganized attachment uniquely correlated to white matter integrity using diffusion tensor imaging

Riem

Hoof

Garrett

et al. 2019

Behavioural Brain Research

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“…As ventricle size and total brain volume are inversely correlated (Horga et al, ), this increased ventricular volume association may be comparable to the link between decreased total brain volume and PRS in the present study. A final structural MRI study reported by Patel et al () examined the effect of rs1625579 genotype on subcortical and callosal volumes and reported evidence of an association between the risk (G) allele and decreased corpus callosum volume in SZ patients only ( n = 362) compared to controls ( n = 490). We did not examine this measure in our sample, although potentially a decrease in corpus callosum volume may contribute to the decrease in overall brain volume reported here.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, we previously observed an association between a MIR137 PRS and memory scores, and between MIR137 PRS and altered neural connectivity during performance of a fMRI working memory task (Cosgrove et al, ). There are conflicting reports of the effect of the rs1625579 SNP on brain volume (Cousijn et al, ; Lett et al, ; Patel et al, ; Rose et al, ); however, to date, the effect of an empirically derived miR‐137 regulated gene score on structural brain measures has not been established. Such investigations into potential associations between genetic pathways and brain‐based correlates of cognitive phenotypes may assist in elucidating pathophysiological mechanisms that act as contributing factors to these cognitive deficits.…”

Section: Introductionmentioning

confidence: 99%

Effects of MiR‐137 genetic risk score on brain volume and cortical measures in patients with schizophrenia and controls

Cosgrove

Mothersill

Whitton

et al. 2018

American J of Med Genetics Pt B

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Multiple genome-wide association studies of schizophrenia have implicated genetic variants within the gene encoding microRNA-137. As risk variants within or regulated by MIR137 have been implicated in memory performance, we investigated the additive effects of schizophrenia-associated risk variants in genes empirically regulated by MIR137 on brain regions associated with memory function. A polygenic risk score (PRS) was calculated (at a p = 0.05 threshold), using this empirically regulated MIR137 gene set, to investigate associations between this PRS and structural brain measures. These measures included total brain volume, cortical thickness, cortical surface area, and hippocampal volume, in a sample of 216 individuals consisting of healthy participants (n = 171) and patients with psychosis (n = 45). We did not observe a significant association between MIR137 PRS and these cortical thickness, surface area or hippocampal volume measures linked to memory function; a significant association between increasing PRS and decreasing total brain volume, independent of diagnosis status (R = 0.008, Beta = -0.09, p = 0.029), was observed. This did not survive correction for multiple testing. In conclusion, our study yielded only suggestive evidence that risk variants interacting with MIR137 impacts on cortical structure.

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“…The rs1625579 T allele was linked to a significant regional effect by decreasing the expression of miRNA-137 and increasing the risk of Sz in nine brain regions. Therefore, the TT genotype was correlated with greater regional volume compared with that of the GG/GT genotype in Sz patients (72,73).…”

Section: Mechanism Of Rs1625579mentioning

confidence: 88%

“…The rs1625579 T allele was linked to a significant regional effect by decreasing the expression of miRNA‐137 and increasing the risk of Sz in nine brain regions. Therefore, the TT genotype was correlated with greater regional volume compared with that of the GG / GT genotype in Sz patients . In addition, other studies confirmed that miRNA‐137 expression was not only regulated by the rs1625579 genotype but was also influenced by the environment, a phenomenon known as ‘gene × environment’ interactions .…”

Section: Mirna‐137mentioning

confidence: 89%

Associations ofmicroRNAsingle nucleotide polymorphisms and disease risk and pathophysiology

2017

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Single nucleotide polymorphisms (SNPs) are genetic variations that contribute to human phenotypes associated with various diseases. SNPs are involved in the regulation of a broad range of physiological and pathological processes, such as cellular senescence, apoptosis, inflammation, and immune response, by upregulating the expression of classical inflammation markers. Recent studies have suggested that SNPs located in gene-encoding microRNAs (miRNAs) affect various aspects of diseases by regulating the expression or activity of miRNAs. In the last few years, miRNA polymorphisms that increase and/or reduce the risk of developing many diseases, such as cancers, autoimmune diseases, and cardiovascular diseases, have attracted increasing attention not only because of their involvement in the pathophysiology of diseases but also because they can be used as prognostic biomarkers for a variety of diseases. In this review, we summarize the relationships between miRNA SNPs and the pathophysiology and risk of diseases.

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MIR137HG risk variant rs1625579 genotype is related to corpus callosum volume in schizophrenia

Cited by 21 publications

References 36 publications

General psychopathology factor and unresolved-disorganized attachment uniquely correlated to white matter integrity using diffusion tensor imaging

General psychopathology factor and unresolved-disorganized attachment uniquely correlated to white matter integrity using diffusion tensor imaging

Effects of MiR‐137 genetic risk score on brain volume and cortical measures in patients with schizophrenia and controls

Associations ofmicroRNAsingle nucleotide polymorphisms and disease risk and pathophysiology

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