An association of Myelin Oligodendrocyte Glycoprotein (MOG) gene variants with white matter volume in pediatric obsessive-compulsive disorder.
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ABSTRACT:
SUBMITTER: Zai G
PROVIDER: S-EPMC7775903 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Obsessive-compulsive disorder (OCD) is a prevalent and often severely disabling illness with onset generally in childhood or adolescence. Although white matter deficits have been implicated in the neurobiology of OCD, few studies have been conducted in pediatric patients when the brain is still developing and have examined their functional correlates. In this study, 23 pediatric OCD patients and 23 healthy volunteers, between the ages of 9 and 17 years, matched for sex, age, handedness, and IQ, received a diffusion tensor imaging exam on a 3T GE system and a brief neuropsychological battery tapping executive functions. Patient symptom severity was assessed using the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). Patients with OCD exhibited significantly greater fractional anisotropy compared to matched controls in the left dorsal cingulum bundle, splenium of the corpus callosum, right corticospinal tract, and left inferior fronto-occipital fasciculus. There were no regions of significantly lower fractional anisotropy in patients compared to controls. Higher fractional anisotropy in the splenium was significantly correlated with greater obsession severity on the CY-BOCS in the subgroup of psychotropic drug-naïve patients. Among patients, there was a significant association between greater fractional anisotropy in the dorsal cingulum bundle and better performance on measures of response inhibition and cognitive control. The overall findings suggest a pattern of greater directional coherence of white matter tracts in OCD very early in the course of illness, which may serve a compensatory mechanism, at least for response inhibition functions typically subserved by the cingulum bundle.
| S-EPMC3473339 | biostudies-other
Project description:Atypical development of frontal-striatal-thalamic circuitry (FSTC) has been hypothesized to underlie the early course of obsessive-compulsive disorder (OCD); however, the development of FSTC white matter tracts remains to be studied in young patients.To address this gap, we scanned 36 patients with pediatric OCD compared to 27 healthy controls, aged 8 to 19 years, with diffusion tensor imaging (DTI) to measure fractional anisotropy (FA), an index of white matter coherence. Tract-based spatial statistics (TBSS) were used to test differential effects of age on FA, across the whole brain, in those with OCD compared to healthy youth, followed by analyses in a priori regions of interest (anterior corpus callosum, anterior cingulum bundle, and anterior limb of the internal capsule [ALIC]) to further characterize developmental differences between groups.Patients with OCD showed more pronounced age-related increases in FA than controls in regions of interest, as well as several other white matter tracts. In patients, greater FA in anterior cingulum bundle correlated with more severe symptoms after controlling for age.Our findings support theories of atypical FSTC maturation in pediatric OCD by providing the first evidence for altered trajectories of white matter development in anterior corpus callosum, anterior cingulum bundle, and ALIC in young patients. Steeper age-related increases of FA in these and other select white matter tracts in OCD, compared to those in healthy controls, may derive from an early delay in white matter development and/or prolonged white matter growth; however, confirmation of these possibilities awaits longitudinal work.
| S-EPMC4323383 | biostudies-literature
Project description:Introduction: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease is a recently described central nervous system (CNS) inflammatory disorder with phenotypic overlap with Neuromyelitis Optica Spectrum Disorder (NMOSD). NMOSD seronegative patients, and those with limited forms of the disorder, become suspects for MOG antibody-associated disease. We describe a multi-ethnic population with MOG antibody seropositivity from the University of British Columbia MS/NMO clinic. Methods: AQP4-antibody seronegative patients presenting 2005-2016 with CNS inflammatory disease suspicious for NMOSD, as well as 20 MS controls, were retrospectively tested for MOG-IgG1 antibodies by live cell-based assay at Oxford Autoimmune Neurology Diagnostic Laboratory (UK) and by a commercial fixed cell-based assay at MitogenDx (Calgary, Canada). Additional MOG seropositive cases were identified through routine clinical interaction (2016-2018) using one of these laboratories. Clinical data was reviewed retrospectively. Results: Retrospective testing identified 21 MOG seropositives (14 by live assay only, 3 by fixed assay only and 4 by both) representing 14% of the "NMOSD suspects" cohort. One multiple sclerosis (MS) control serum was MOG seropositive. Twenty additional MOG positive cases were identified prospectively. Of 42 patients (27 female), median disease onset age was 29 years (range 3-62; 9 pediatric cases), 20 (47%) were non-Caucasian, and 3 (7%) had comorbid autoimmune disease. Most common onset phenotypes were optic neuritis (23, 55%; 8 bilateral) and myelitis (9, 21%; 6 longitudinally extensive) Three of the patients in our cohort experienced cortical encephalitis; two presented with seizures. Onset was moderate-severe in 64%, but 74% had good response to initial steroid therapy. Cumulative relapse probability for the MOG positive group at 1 year was 0.428 and at 4 years was 0.628. Most had abnormal brain imaging, including cortical encephalitis and poorly demarcated subcortical and infratentorial lesions. Few "classic MS" lesions were seen. Optic nerve lesions (frequently bilateral) were long and predominantly anterior, but 5 extended to the chiasm. Spinal cord lesions were long and short, with involvement of multiple spinal regions simultaneously, including the conus medullaris. Conclusions: Our MOG seropositive patients display phenotypes similar to previous descriptions, including cortical lesions with seizures and conus medullaris involvement. Many patients relapsed, predominantly in a different CNS location from onset. Serologic data from two different cell-based antibody assays highlight the discrepancies between live and fixed testing for MOG antibodies.
| S-EPMC7835710 | biostudies-literature
Project description:BACKGROUND:New-generation, cell-based assays have demonstrated a robust association of serum autoantibodies to full-length human myelin oligodendrocyte glycoprotein (MOG-IgG) with (mostly recurrent) optic neuritis, myelitis, and brainstem encephalitis, as well as with neuromyelitis optica (NMO)-like or acute-disseminated encephalomyelitis (ADEM)-like presentations. However, only limited data are yet available on cerebrospinal fluid (CSF) findings in MOG-IgG-associated encephalomyelitis (MOG-EM; also termed MOG antibody-associated disease, MOGAD). OBJECTIVE:To describe systematically the CSF profile in children with MOG-EM. MATERIAL AND METHODS:Cytological and biochemical findings (including white cell counts [WCC] and differentiation; frequency and patterns of oligoclonal bands; IgG/IgM/IgA and albumin concentrations and CSF/serum ratios; intrathecal IgG/IgM/IgA fractions; locally produced IgG/IgM/IgA concentrations; immunoglobulin class patterns; IgG/IgA/IgM reibergrams; Link index; measles/rubella/zoster [MRZ] reaction; other anti-viral and anti-bacterial antibody indices; CSF total protein; CSF L-lactate) from 108 lumbar punctures in 80 pediatric patients of mainly Caucasian descent with MOG-EM were analyzed retrospectively. RESULTS:Most strikingly, CSF-restricted oligoclonal IgG bands, a hallmark of multiple sclerosis (MS), were absent in 89% of samples (N = 96), and the MRZ reaction, the most specific laboratory marker of MS known so far, in 100% (N = 29). If present at all, intrathecal IgG synthesis was low, often transient and mostly restricted to acute attacks. Intrathecal IgM synthesis was present in 21% and exclusively detectable during acute attacks. CSF WCC were elevated in 54% of samples (median 40 cells/?l; range 6-256; mostly lymphocytes and monocytes; >?100/?l in 11%). Neutrophils were present in 71% of samples; eosinophils, activated lymphocytes, and plasma cells were seen only rarely (all <?7%). Blood-CSF barrier dysfunction (as indicated by an elevated albumin CSF/serum ratio) was present in 46% of all samples (N = 79) and at least once in 48% of all patients (N = 67) tested. CSF alterations were significantly more frequent and/or more pronounced in patients with acute spinal cord or brain disease than in patients with acute ON and varied strongly depending on attack severity. CSF L-lactate levels correlated significantly with the spinal cord lesions load (measured in vertebral segments) in patients with acute myelitis (p = 0.0099). An analysis of pooled data from the pediatric and the adult cohort showed a significant relationship of QAlb (p < 0.0005), CST TP (p < 0.0001), and CSF L-lactate (p < 0.0003) during acute attacks with age. CONCLUSION:MOG-IgG-associated EM in children is characterized by CSF features that are distinct from those in MS. With regard to most parameters, no marked differences between the pediatric cohort and the adult cohort analyzed in Part 1 were noted. Our findings are important for the differential diagnosis of pediatric MS and MOG-EM and add to the understanding of the immunopathogenesis of this newly described autoimmune disease.
| S-EPMC7470445 | biostudies-literature
Project description:ObjectiveTo identify the most prominent and replicable fractional anisotropy (FA) alterations of white matter associated with obsessive-compulsive disorder (OCD) in tract-based spatial statistics (TBSS) studies.MethodsWe reviewed previous TBSS studies (n = 20) in OCD and performed a meta-analysis (n = 16) of FA differences.ResultsNo between-group differences in FA were detected in the pooled meta-analysis. However, reduced FA was identified in the genu and anterior body of corpus callosum (CC) in adult OCD. FA reductions in the anterior body of CC were associated with a later age of onset in adult patients with OCD. For pediatric OCD, decreased FA in earlier adolescence and increased FA in later adolescence were seemingly related to an altered trajectory of brain maturation.ConclusionsAbsent in the pooled sample but robust in adults, disrupted microstructural organization in the anterior part of CC indicates a bias of deficits toward connections in interhemispheric connections of rostral neocortical regions, which could lead to deficits of interhemispheric communication and thus contribute to cognitive and emotional deficits in adult OCD. The correlation between FA in the anterior body of CC and older illness onset suggests that patients with later adult onset of illness may represent a biologically distinct subgroup. For pediatric OCD, alterations in neurodevelopmental maturation may contribute to inconsistent patterns of FA alteration relative to controls during adolescence. While most studies of OCD have emphasized alterations of within hemisphere fronto-striatal circuits, these results indicate that between hemisphere connectivity of this circuitry may also represent important pathophysiology of the illness.
| S-EPMC7882176 | biostudies-literature
Project description:Obsessive-compulsive disorder (OCD) is a complex and severe psychiatric disorder whose pathogenesis is not fully understood. Recent studies have shown white matter (WM) alterations in adults with OCD, but the results have been inconsistent. The present study investigated WM structure in OCD patients with the hypothesis that large-scale brain networks may be disrupted in OCD. A total of 24 patients with OCD and 23 healthy controls (HCs) were scanned with diffusion tensor imaging. A tract-based spatial statistics (TBSS) approach was used to detect differences across the whole brain in patients with OCD vs HCs; post hoc fiber tractography was applied to characterize developmental differences between the two groups. Relative to HCs, patients with OCD had lower fractional anisotropy (FA) values in the corpus callosum (CC), left anterior corona radiata (ACR), left superior corona radiata (SCR) and left superior longitudinal fasciculus (SLF), and higher radial diffusivity in the genu and body of CC. Among the TBSS de-projected region of interest results, compared with HCs, patients with OCD showed lower of the mean FA values of fiber bundles passing though the SLF, and shorter lengths of ACR, SCR and CC. In conclusion, this study provides novel evidence of widespread microstructural alterations in OCD and suggests that OCD may involve abnormalities affecting a broader network of regions than commonly believed.
| S-EPMC5416668 | biostudies-literature
Project description:Intracortical myelin is involved in speeding and synchronizing neural activity of the cerebral cortex and has been found to be disrupted in various psychiatric disorders. However, its role in obsessive-compulsive disorder (OCD) has remained unknown. In this study, we investigated the alterations in intracortical myelin and their association with white matter (WM) microstructural abnormalities in OCD. T1-weighted and diffusion-weighted brain images were obtained for 51 medication-naïve patients with OCD and 26 healthy controls (HCs). The grey/white matter contrast (GWC) was calculated from T1-weighted signal intensities to characterize the intracortical myelin profile in OCD. Diffusion parameters, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD), were extracted from diffusion-weighted images to examine the WM microstructure in OCD. Compared with HCs, patients with OCD showed increased GWC in the bilateral orbitofrontal, cuneus, lingual and fusiform gyrus, left anterior cingulate, left superior parietal, right inferior parietal, and right middle frontal cortices, suggesting reduced intracortical myelin. Patients with OCD also showed decreased FA in several WM regions, with a topology corresponding to the GWC alterations. In both groups, the mean GWC of the significant clusters in between-group GWC analysis was correlated negatively with the mean FA of the significant clusters in between-group FA analysis. In patients with OCD, the FA of a cluster in the right cerebellum correlated negatively with the Yale-Brown obsessive-compulsive scale scores. Our results suggest that abnormal intracortical and WM myelination could be the microstructural basis for the brain connectivity alterations and disrupted inhibitory control in OCD.
| S-EPMC9421450 | biostudies-literature
Project description:BackgroundMyelin oligodendrocyte glycoprotein antibody-associated encephalomyelitis (MOG-EM; also termed MOG antibody-associated disease, MOGAD) is the most important differential diagnosis of both multiple sclerosis and neuromyelitis optica spectrum disorders. A recent proposal for new diagnostic criteria for MOG-EM/MOGAD explicitly recommends the use of immunoglobulin G subclass 1 (IgG1)- or IgG crystallizable fragment (Fc) region-specific assays and allows the use of heavy-and-light-chain-(H+L) specific assays for detecting MOG-IgG. By contrast, the utility of MOG-IgG3-specific testing has not been systematically evaluated.ObjectiveTo assess whether the use of MOG-IgG3-specific testing can improve the sensitivity of MOG-IgG testing.MethodsRe-testing of 22 patients with a definite diagnosis of MOG-EM/MOGAD and clearly positive MOG-IgG status initially but negative or equivocal results in H+L- or Fc-specific routine assays later in the disease course (i.e. patients with spontaneous or treatment-driven seroreversion).ResultsIn accordance with previous studies that had used MOG-IgG1-specific assays, IgG subclass-specific testing yielded a higher sensitivity than testing by non-subclass-specific assays. Using subclass-specific secondary antibodies, 26/27 supposedly seroreverted samples were still clearly positive for MOG-IgG, with MOG-IgG1 being the most frequently detected subclass (25/27 [93%] samples). However, also MOG-IgG3 was detected in 14/27 (52%) samples (from 12/22 [55%] patients). Most strikingly, MOG-IgG3 was the predominant subclass in 8/27 (30%) samples (from 7/22 [32%] patients), with no unequivocal MOG-IgG1 signal in 2 and only a very weak concomitant MOG-IgG1 signal in the other six samples. By contrast, no significant MOG-IgG3 reactivity was seen in 60 control samples (from 42 healthy individuals and 18 patients with MS). Of note, MOG-IgG3 was also detected in the only patient in our cohort previously diagnosed with MOG-IgA+/IgG- MOG-EM/MOGAD, a recently described new disease subvariant. MOG-IgA and MOG-IgM were negative in all other patients tested.ConclusionsIn some patients with MOG-EM/MOGAD, MOG-IgG is either exclusively or predominantly MOG-IgG3. Thus, the use of IgG1-specific assays might only partly overcome the current limitations of MOG-IgG testing and-just like H+L- and Fcγ-specific testing-might overlook some genuinely seropositive patients. This would have potentially significant consequences for the management of patients with MOG-EM/MOGAD. Given that IgG3 chiefly detects proteins and is a strong activator of complement and other effector mechanisms, MOG-IgG3 may be involved in the immunopathogenesis of MOG-EM/MOGAD. Studies on the frequency and dynamics as well as the clinical and therapeutic significance of MOG-IgG3 seropositivity are warranted.
| S-EPMC11233316 | biostudies-literature
Project description:Purpose: To describe a Japanese girl with unilateral optic neuritis who was seropositive for the anti-myelin-oligodendrocyte glycoprotein (MOG). Serial recordings of the pattern visual evoked potentials (pVEPs) were made to follow the dynamic changes of the disease activity. Observations: A 5-year-old girl developed a sudden reduction of vision and deep ocular pain in her right eye. On examination at our university hospital, the best-corrected visual acuity (BCVA) was light perception, and a swelling of the optic disc and tortuous vessels at the posterior pole of the right eye were observed. MRI demonstrated that her right optic nerve was hyperintense on short TI inversion recovery (STIR) sequence. A diagnosis of right papillitis was made, and she was treated with steroid pulse therapy followed by a gradual tapering of oral prednisolone. The visual acuity decreased to no light perception and plasmapheresis combined with high-dose intravenous immunoglobulin therapy was performed. The decimal visual acuity rapidly improved and recovered to 1.2, and no recurrence was observed for at least 1 year. On day 19, she was found to be anti-MOG antibody positive and anti-Aquaporin 4 antibody negative. pVEPs were recorded during the course of the disease process which showed the dynamic changes of the physiology of the visual pathways. The implicit times of the N75 and P100 components were prolonged in the right eye in the acute phase. The right visual acuity remained at 1.2 for at least 1 year, but the implicit times of the N75 and P100 components of the pVEPs of the right eye were still prolonged compared to left eye. Conclusion: Our findings indicate a positive relationship between the anti-MOG antibodies-positivity and the prolonged pVEPs. Further analyses of the pVEPs and other clinical findings of the optic neuritis are needed to establish the clinical significance of the anti-MOG antibodies positivity and optic neuritis for the diagnosis, treatment, and prognosis for this disease.
| S-EPMC6931555 | biostudies-literature
Project description:In recent years, diffusion tensor imaging (DTI) studies have detected subtle microstructural abnormalities of white matter (WM) in obsessive-compulsive disorder (OCD). However, findings have been inconsistent, and it is unclear whether WM abnormalities are related to cognitive processes. The aim of this study was to explore the relationship of WM alterations with cognitive variables in OCD in order to investigate the structural correlates of behaviorally relevant features of the disorder.We compared DTI-derived fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) measures between OCD patients (n = 16) and healthy controls (n = 18) using a whole-brain tract-based spatial statistics (TBSS) approach. We also explored the correlations of WM alterations with clinical and cognitive variables.Patients with OCD demonstrated increases in MD in the bilateral posterior corona radiata; left anterior corona radiata; bilateral superior longitudinal fasciculus; genu, body, and splenium of the corpus callosum; and left posterior limb of the internal capsule. An increase in RD values was also found in some of the same tracts (right posterior corona radiata, right superior longitudinal fasciculus, left anterior corona radiata, and corpus callosum). Furthermore, increased MD value in the internal capsule was correlated with the percentage of errors made during a target detection task, which was greater in the OCD group overall.These findings indicate that OCD patients show greater diffusivity in several white-matter regions. The correlation between cognitive performance and diffusivity in the internal capsule suggests that microstructural WM alternations may have functional consequences for the disorder.
| S-EPMC4831422 | biostudies-other