Myelin oligodendrocyte glycoprotein (MOG) gene is associated with obsessive‐compulsive disorder

Zai, Gwyneth; Bezchlibnyk, Yarema B.; Richter, Margaret A.; Arnold, Paul; Burroughs, Eliza; Barr, Cathy L.; Kennedy, James L.

doi:10.1002/ajmg.b.30077

Cited by 67 publications

(35 citation statements)

References 29 publications

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“…Severe depression, bipolar disorder, and other neuropsychiatric disorders have also been associated with myelination deficits (Aston et al, 2005;Bartzokis, 2005;Beasley et al, 2005;Hamidi et al, 2004;McDonald et al, 2004;Tkachev et al, 2003;Uranova et al, 2005;Uranova et al, 2004;Wang et al, 2004b;Zai et al, 2004). If, as we suggest, treatment with atypical antipsychotics can mitigate myelination deficits, then such treatment could also mitigate similar deficits in these other psychiatric conditions.…”

Section: Discussionmentioning

confidence: 73%

Differential effects of typical and atypical antipsychotics on brain myelination in schizophrenia

Bartzokis

Nuechterlein

et al. 2007

Schizophrenia Research

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Context-Imaging and post-mortem studies provide converging evidence that patients with schizophrenia have a dysregulated developmental trajectory of frontal lobe myelination even in adulthood. Atypical antipsychotics have been shown to have a wide spectrum of efficacy across multiple psychiatric diseases and to be particularly efficacious in treatment resistant cases of disorders such as schizophrenia.Objective-To test the a priori hypothesis that antipsychotic medications may differentially impact frontal lobe myelination in patients with schizophrenia.Design, setting, and participants-Participants ranged in age from 18-35 years, were all male, and were recruited by a single group of investigators using the same criteria. Two cohorts of subjects with schizophrenia early in their disease who were treated either with oral risperidone (Ris) or fluphenazine decanoate (Fd) were imaged in conjunction with cohorts of healthy controls. Each cohort was imaged using a different MRI instrument using identical imaging sequences. Main outcome measure-MRI measures of frontal lobe white matter volume.Results-We estimated differences due to differences in the MRI instruments used in the two studies in the two healthy control groups matched to the patient samples, adjusting for age and other covariates. We then statistically removed those differences (which we assumed were instrument artifacts) from the data in the schizophrenia samples by subtraction. Relative to the differences seen in controls, the two groups of schizophrenic patients differed in their pattern of frontal lobe structure with the Ris-treated group having significantly larger white matter volume than the Fd group.

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Section: Discussionmentioning

confidence: 73%

Differential effects of typical and atypical antipsychotics on brain myelination in schizophrenia

Bartzokis

Nuechterlein

et al. 2007

Schizophrenia Research

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“…Although Song et al (2003) suggested a higher RD to be associated with demyelination, others have shown that the interpretation of changes in RD and AD needs careful consideration, due to the inherent disbalance between fiber thickness and imaging resolution (WheelerKingshott and Cercignani, 2009). Although a few genetic studies suggested myelination in the OCD pathophysiology (Zai et al, 2004;Stewart et al, 2007), we can only speculate about possible disruption of myelin integrity contributing to the white matter abnormalities in the left cingulum bundle. A similar pattern of lower FA in combination with higher RD (and normal AD values) has also been reported for autism, schizophrenia, and depression Ashtari et al, 2007;Lee et al, 2007;Michael et al, 2008;Seal et al, 2008;Whitford et al, 2010;Korgaonkar et al, 2011).…”

Section: Discussionmentioning

confidence: 86%

Mild White Matter Changes in Un-Medicated Obsessive-Compulsive Disorder Patients and Their Unaffected Siblings

Fan

Heuvel

Cath

et al. 2017

European Neuropsychopharmacology

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Objective: Obsessive-compulsive disorder (OCD) is a common neuropsychiatric disorder with moderate genetic influences and white matter abnormalities in frontal-striatal and limbic regions. Inconsistencies in reported white matter results from diffusion tensor imaging (DTI) studies can be explained, at least partly, by medication use and between-group differences in disease profile and stage. We used a family design aiming to establish whether white matter abnormalities, if present in un-medicated OCD patients, also exist in their unaffected siblings.Method: Forty-four OCD patients, un-medicated for at least the past 4 weeks, 15 of their unaffected siblings, and 37 healthy controls (HC) underwent DTI using a 3-Tesla MRI-scanner. Data analysis was done using tract-based spatial statistics (TBSS). Fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) values were compared within seven skeletonised regions of interest (ROIs), i.e., corpus callosum, bilateral cingulum bundle, bilateral inferior longitudinal fasciculus/ frontal-occipital fasciculus (ILF/FOF) and bilateral superior longitudinal fasciculus (SLF).Results: Un-medicated OCD patients, compared with HC, had significantly lower FA in the left cingulum bundle. FA was trend-significantly lower in all other ROIs, except for the corpus callosum. Significant three-group differences in FA (and in RD at trend-significant level) were observed in the left cingulum bundle, with the unaffected siblings representing an intermediate group between OCD patients and HC.Conclusions: OCD patients showed lower FA in the left cingulum bundle, partly driven by trend-significantly higher values in RD. Since the unaffected siblings were found to be an intermediate group between OCD patients and HC, this white matter alteration may be considered an endophenotype for OCD.

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“…The authors suggested that the potentially autoimmune demyelinating role of this molecule, as a target autoantigen, could hypothetically be as an inductor of OCD, via demyelination in the frontal lobe or in other neuroanatomical regions. 152 The complexity of this model, in which a true autoimmune mechanism would be causing OCD, as well as the lack of evidence supporting it, argues for further studies.…”

Section: Environmental Factorsmentioning

confidence: 98%

“…140 However, these early findings have not been consistently replicated, and there is now considerable controversy regarding this relationship. 150,151 Finally, one recent study 152 found an association between a variant in the myelin oligodendrocyte glycoprotein (MOG) gene, a component of the myelin sheath, and OCD. The authors suggested that the potentially autoimmune demyelinating role of this molecule, as a target autoantigen, could hypothetically be as an inductor of OCD, via demyelination in the frontal lobe or in other neuroanatomical regions.…”

Section: Environmental Factorsmentioning

confidence: 99%

Obsessive-compulsive disorder phenotypes: implications for genetic studies

et al. 2004

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Obsessive-compulsive disorder (OCD) clinical presentation is remarkably diverse, and can vary both within and across patients over time. This variability in the phenotypic expression has led to the hypothesis that OCD is a heterogeneous disorder and that this heterogeneity obscures the findings of clinical, natural history and treatment response studies and complicates the search for vulnerability genes. A complete understanding of what comprises OCD and the underlying etiological mechanisms will require a dramatic change in how the disorder is conceptualized. In this review, several different approaches that may represent the first steps in this reconceptualization are discussed. These approaches include (1) narrowing the phenotype to identify categorically defined more homogeneous and mutually exclusive subtypes of OCD, (2) considering OC symptom dimensions as quantitative components of the more complex OCD phenotype and (3) broadening the phenotype to include other etiologically related conditions. A combined dimensional approach within distinctive subgroups is proposed as probably the most effective in helping to identify the heritable components of OCD. By identifying heritable components of OCD, it should be possible to find genes for these separate components. The review continues with the illustration of the possible role of some epigenetic risk and protective factors in the OCD presentation and the relevance of examining associated traits and/or endophenotypes to enhance our ability to understand the genetic basis of OCD. To conclude, we discuss the variability in treatment outcome and the significance of the development of specific pharmacological and/or behavioral based therapies tailored to each of these phenotypes. Molecular Psychiatry (2005) 10, 258-275.

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Myelin oligodendrocyte glycoprotein (MOG) gene is associated with obsessive‐compulsive disorder

Cited by 67 publications

References 29 publications

Differential effects of typical and atypical antipsychotics on brain myelination in schizophrenia

Differential effects of typical and atypical antipsychotics on brain myelination in schizophrenia

Mild White Matter Changes in Un-Medicated Obsessive-Compulsive Disorder Patients and Their Unaffected Siblings

Obsessive-compulsive disorder phenotypes: implications for genetic studies

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