Glutathione metabolism in the prefrontal brain of adults with high-functioning autism spectrum disorder: an MRS study

Endres, Dominique; Elst, Ludger Tebartz van; Meyer, Simon A.; Feige, Bernd; Nickel, Kathrin; Bubl, Anna; Riedel, Andreas; Ebert, Dieter; Lange, Thomas; Glauche, Volkmar; Biscaldi, Monica; Philipsen, Alexandra; Maier, Simon; Perlov, Evgeniy

doi:10.1186/s13229-017-0122-3

Cited by 36 publications

(32 citation statements)

References 70 publications

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“…We included 36 patients with ASD who had received a lumbar puncture at our tertiary care hospital from 2010 to 2018. The patients were diagnosed by experienced senior physicians following German guidelines [ 30 ] as described in detail in earlier papers [ 31 , 32 ] and were classified following ICD-10. Patients with neurodegenerative disorders were excluded from the study; examples include mild cognitive impairment (ICD-10: F06.7) or dementia (ICD-10: F03), substance abuse (ICD-10: F1x.2), or severe neurological diseases other than epilepsy (because of its known association with ASD) [ 33 , 34 ].…”

Section: Participants and Methodsmentioning

confidence: 99%

Cerebrospinal Fluid Findings of 36 Adult Patients with Autism Spectrum Disorder

et al. 2020

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Autism spectrum disorder (ASD) is a common neurodevelopmental disorder characterized by difficulties with social interaction, repetitive behavior, and additional features, such as special interests. Its precise etiology is unclear. Recently, immunological mechanisms, such as maternal autoantibodies/infections, have increasingly been the subject of discussion. Cerebrospinal fluid (CSF) investigations play a decisive role in the detection of immunological processes in the brain. This study therefore retrospectively analyzed the CSF findings of adult patients with ASD. CSF basic measures (white blood cell count, total protein, albumin quotient, immunoglobulin G (IgG) index, and oligoclonal bands) and various antineuronal antibody findings of 36 adult patients with ASD, who had received lumbar puncture, were compared with an earlier described mentally healthy control group of 39 patients with idiopathic intracranial hypertension. CSF protein concentrations and albumin quotients of patients with ASD were significantly higher as compared to controls (age corrected: p = 0.003 and p = 0.004, respectively); 17% of the patients with ASD showed increased albumin quotients. After correction for age and gender, the group effect for total protein remained significant (p = 0.041) and showed a tendency for albumin quotient (p = 0.079). In the CSF of two ASD patients, an intrathecal synthesis of anti-glutamate decarboxylase 65 (GAD65) antibodies was found. In total, more of the ASD patients (44%) presented abnormal findings in CSF basic diagnostics compared to controls (18%; p = 0.013). A subgroup of the patients with adult ASD showed indication of a blood–brain barrier dysfunction, and two patients displayed an intrathecal synthesis of anti-GAD65 antibodies; thus, the role of these antibodies in patients with ASD should be further investigated. The results of the study are limited by its retrospective and open design. The group differences in blood–brain barrier markers could be influenced by a different gender distribution between ASD patients and controls.

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Section: Participants and Methodsmentioning

confidence: 99%

Cerebrospinal Fluid Findings of 36 Adult Patients with Autism Spectrum Disorder

et al. 2020

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“…The spectroscopic analysis was conducted as described in earlier studies [15–17, 55, 57]. We used the linear combination of model spectra (LCModel) algorithm to ensure investigator-independent spectral analysis [44, 45].…”

Section: Participants and Methodsmentioning

confidence: 99%

Neurochemical sex differences in adult ADHD patients: an MRS study

et al. 2019

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ObjectiveAttention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Relevant sex differences in symptomatology are discussed. This study compared brain neurometabolism in the anterior cingulate cortex (ACC) and left cerebellar hemisphere in age- and IQ-matched adult male (mADHD) and female (fADHD) ADHD patients.MethodsWe studied 48 (ACC) and 42 (cerebellum) male/female pairs of stimulant-free patients with adult ADHD. Single voxel magnetic resonance spectroscopy (MRS) was used to investigate creatine (Cre), total choline (t-Cho), glutamate + glutamine (Glx), N-acetylaspartate, and myo-inositol. The mADHD and fADHD groups were compared using robust linear regression. The level of significance was corrected for multiple tests using the Benjamini-Hochberg approach.ResultsFor the ACC, the signals of Cre (p = 0.008) and t-Cho (p = 0.004) showed significant effects of the age covariate as well as an interaction of sex and age (Cre: p = 0.033; t-Cho: p = 0.040). For the Glx signal, an interaction of sex and age could also be observed (p = 0.033). For cerebellar neurometabolites, the signals of t-Cho (p = 0.049) and Glx (p = 0.049) showed significant effects of the factor sex.ConclusionThis is the largest study yet to analyze sex differences in brain neurochemistry in adult patients with ADHD. Different age-dependent t-Cho signals in the ACC might be associated with delayed myelinization in mADHD. Further MRS studies in adult ADHD, accounting for possible sex effects, are warranted to validate the present findings.

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“…Hence, although the overall trend is for lower GABA+ in ASD, it seems that results are inconsistent, owing perhaps to differences in experimental procedures and analysis methods, regions of interest (ROIs), and sample characteristics, as summarized in several recent reviews [Ajram et al, 2019;Ford & Crewther, 2016;Schür et al, 2016]. In the case of Glx, results are even less conclusive, with studies reporting reduced [Bernardi et al, 2011;Corrigan et al, 2013;DeVito et al, 2007;Hegarty et al, 2018;Horder et al, 2013Horder et al, , 2018Kubas et al, 2012;Tebartz Van Elst et al, 2014], equivalent [Ajram et al, 2017;Aoki et al, 2012;Brix et al, 2015;Carvalho Pereira et al, 2018;Endres et al, 2017;Friedman et al, 2006;Goji et al, 2017;Hardan et al, 2008;Horder et al, 2018;Ito et al, 2017;Libero et al, 2016;Mikkelsen et al, 2017;Robertson et al, 2016], or increased [Bejjani et al, 2012;Brown, Singel, Hepburn, & Rojas, 2013;Doyle-Thomas et al, 2014;Page et al, 2006] levels in ASD. In the current study, we sought to extend previous results by measuring GABA+ and Glx simultaneously using current methodology, in a relatively large sample of well-characterized individuals with ASD, including previously unexamined ROIs, and testing the functional relevance of neurometabolite levels by correlating individual differences in MRS measures with behavior and ASD symptomatology.…”

Section: Introductionmentioning

confidence: 99%

Concentrations of Cortical GABA and Glutamate in Young Adults With Autism Spectrum Disorder

et al. 2020

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The balance of excitation and inhibition in neural circuits is hypothesized to be increased in autism spectrum disorder, possibly mediated by altered signaling of the inhibitory neurotransmitter γaminobutyric acid (GABA), yet empirical evidence in humans is inconsistent. We used edited magnetic resonance spectroscopy (MRS) to quantify signals associated with both GABA and the excitatory neurotransmitter glutamate in multiple regions of the sensory and sensorimotor cortex, including primary visual, auditory, and motor areas in adult individuals with autism and in neurotypical controls. Despite the strong a priori hypothesis of reduced GABA in autism spectrum disorder, we found no group differences in neurometabolite concentrations in any of the examined

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Glutathione metabolism in the prefrontal brain of adults with high-functioning autism spectrum disorder: an MRS study

Cited by 36 publications

References 70 publications

Cerebrospinal Fluid Findings of 36 Adult Patients with Autism Spectrum Disorder

Cerebrospinal Fluid Findings of 36 Adult Patients with Autism Spectrum Disorder

Neurochemical sex differences in adult ADHD patients: an MRS study

Concentrations of Cortical GABA and Glutamate in Young Adults With Autism Spectrum Disorder

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