Brain glutathione and GABA+ levels in autistic children / Yulu SONG in Autism Research, 17-3 (March 2024)  

Public ISBD [article]  inAutism Research > 17-3 (March 2024) . - p.512-528 Titre : Brain glutathione and GABA+ levels in autistic children Type de document : texte imprimé Auteurs : Yulu SONG, Auteur ; Kathleen E. HUPFELD, Auteur ; Christopher W. DAVIES-JENKINS, Auteur ; Helge J. ZÖLLNER, Auteur ; Saipavitra MURALI-MANOHAR, Auteur ; Abdul Nashirudeen MUMUNI, Auteur ; Deana CROCETTI, Auteur ; Vivek YEDAVALLI, Auteur ; Georg OELTZSCHNER, Auteur ; Natalie ALESSI, Auteur ; Mitchell A. BATSCHELETT, Auteur ; Nicolaas A.J. PUTS, Auteur ; Stewart H. MOSTOFSKY, Auteur ; Richard A.E. EDDEN, Auteur Article en page(s) : p.512-528 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Abstract Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social communication challenges and repetitive behaviors. Altered neurometabolite levels, including glutathione (GSH) and gamma-aminobutyric acid (GABA), have been proposed as potential contributors to the biology underlying ASD. This study investigated whether cerebral GSH or GABA levels differ between a cohort of children aged 8-12 years with ASD (n = 52) and typically developing children (TDC, n = 49). A comprehensive analysis of GSH and GABA levels in multiple brain regions, including the primary motor cortex (SM1), thalamus (Thal), medial prefrontal cortex (mPFC), and supplementary motor area (SMA), was conducted using single-voxel HERMES MR spectroscopy at 3T. The results revealed no significant differences in cerebral GSH or GABA levels between the ASD and TDC groups across all examined regions. These findings suggest that the concentrations of GSH (an important antioxidant and neuromodulator) and GABA (a major inhibitory neurotransmitter) do not exhibit marked alterations in children with ASD compared to TDC. A statistically significant positive correlation was observed between GABA levels in the SM1 and Thal regions with ADHD inattention scores. No significant correlation was found between metabolite levels and hyper/impulsive scores of ADHD, measures of core ASD symptoms (ADOS-2, SRS-P) or adaptive behavior (ABAS-2). While both GSH and GABA have been implicated in various neurological disorders, the current study provides valuable insights into the specific context of ASD and highlights the need for further research to explore other neurochemical alterations that may contribute to the pathophysiology of this complex disorder. En ligne : https://doi.org/10.1002/aur.3097 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=525 [article] Brain glutathione and GABA+ levels in autistic children [texte imprimé] / Yulu SONG, Auteur ; Kathleen E. HUPFELD, Auteur ; Christopher W. DAVIES-JENKINS, Auteur ; Helge J. ZÖLLNER, Auteur ; Saipavitra MURALI-MANOHAR, Auteur ; Abdul Nashirudeen MUMUNI, Auteur ; Deana CROCETTI, Auteur ; Vivek YEDAVALLI, Auteur ; Georg OELTZSCHNER, Auteur ; Natalie ALESSI, Auteur ; Mitchell A. BATSCHELETT, Auteur ; Nicolaas A.J. PUTS, Auteur ; Stewart H. MOSTOFSKY, Auteur ; Richard A.E. EDDEN, Auteur . - p.512-528. Langues : Anglais (eng) in Autism Research > 17-3 (March 2024) . - p.512-528 Index. décimale : PER Périodiques Résumé : Abstract Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social communication challenges and repetitive behaviors. Altered neurometabolite levels, including glutathione (GSH) and gamma-aminobutyric acid (GABA), have been proposed as potential contributors to the biology underlying ASD. This study investigated whether cerebral GSH or GABA levels differ between a cohort of children aged 8-12 years with ASD (n = 52) and typically developing children (TDC, n = 49). A comprehensive analysis of GSH and GABA levels in multiple brain regions, including the primary motor cortex (SM1), thalamus (Thal), medial prefrontal cortex (mPFC), and supplementary motor area (SMA), was conducted using single-voxel HERMES MR spectroscopy at 3T. The results revealed no significant differences in cerebral GSH or GABA levels between the ASD and TDC groups across all examined regions. These findings suggest that the concentrations of GSH (an important antioxidant and neuromodulator) and GABA (a major inhibitory neurotransmitter) do not exhibit marked alterations in children with ASD compared to TDC. A statistically significant positive correlation was observed between GABA levels in the SM1 and Thal regions with ADHD inattention scores. No significant correlation was found between metabolite levels and hyper/impulsive scores of ADHD, measures of core ASD symptoms (ADOS-2, SRS-P) or adaptive behavior (ABAS-2). While both GSH and GABA have been implicated in various neurological disorders, the current study provides valuable insights into the specific context of ASD and highlights the need for further research to explore other neurochemical alterations that may contribute to the pathophysiology of this complex disorder. En ligne : https://doi.org/10.1002/aur.3097 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=525

Concentrations of Cortical GABA and Glutamate in Young Adults With Autism Spectrum Disorder / Tamar KOLODNY in Autism Research, 13-7 (July 2020)  

Public ISBD [article]  inAutism Research > 13-7 (July 2020) . - p.1111-1129 Titre : Concentrations of Cortical GABA and Glutamate in Young Adults With Autism Spectrum Disorder Type de document : texte imprimé Auteurs : Tamar KOLODNY, Auteur ; Michael-Paul SCHALLMO, Auteur ; Jennifer GERDTS, Auteur ; Richard A.E. EDDEN, Auteur ; Raphael A. BERNIER, Auteur ; Scott O. MURRAY, Auteur Article en page(s) : p.1111-1129 Langues : Anglais (eng) Mots-clés : auditory cortex  autism spectrum disorders  glutamate  magnetic resonance spectroscopy  sensorimotor cortex  visual cortex  ?-aminobutyric acid Index. décimale : PER Périodiques Résumé : 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 γ-aminobutyric 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 regions and no correlations of MRS measure with psychophysical visual sensitivity or autism symptomatology. We demonstrate high data quality that is comparable across groups, with a relatively large sample of well-characterized participants, and use Bayesian statistics to corroborate the lack of any group differences. We conclude that levels of GABA and Glx (glutamate, glutamine, and glutathione) in the sensory and sensorimotor cortex, as measured with MRS at 3T, are comparable in adults with autism and neurotypical individuals. Autism Res 2020, 13: 1111-1129. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: γ-Aminobutyric acid (GABA) and glutamate are the main inhibitory and excitatory neurotransmitters in the human brain, respectively, and their balanced interaction is necessary for neural function. Previous research suggests that the GABA and glutamate systems might be altered in autism. In this study, we used magnetic resonance spectroscopy to measure concentrations of these neurotransmitters in the sensory areas in the brains of young adults with autism. In contradiction to the common hypothesis of reduced GABA in autism, we demonstrate that concentrations of both GABA and glutamate, in all the brain regions examined, are comparable in individuals with autism and in neurotypical adults. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.2300 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=429 [article] Concentrations of Cortical GABA and Glutamate in Young Adults With Autism Spectrum Disorder [texte imprimé] / Tamar KOLODNY, Auteur ; Michael-Paul SCHALLMO, Auteur ; Jennifer GERDTS, Auteur ; Richard A.E. EDDEN, Auteur ; Raphael A. BERNIER, Auteur ; Scott O. MURRAY, Auteur . - p.1111-1129. Langues : Anglais (eng) in Autism Research > 13-7 (July 2020) . - p.1111-1129 Mots-clés : auditory cortex  autism spectrum disorders  glutamate  magnetic resonance spectroscopy  sensorimotor cortex  visual cortex  ?-aminobutyric acid Index. décimale : PER Périodiques Résumé : 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 γ-aminobutyric 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 regions and no correlations of MRS measure with psychophysical visual sensitivity or autism symptomatology. We demonstrate high data quality that is comparable across groups, with a relatively large sample of well-characterized participants, and use Bayesian statistics to corroborate the lack of any group differences. We conclude that levels of GABA and Glx (glutamate, glutamine, and glutathione) in the sensory and sensorimotor cortex, as measured with MRS at 3T, are comparable in adults with autism and neurotypical individuals. Autism Res 2020, 13: 1111-1129. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: γ-Aminobutyric acid (GABA) and glutamate are the main inhibitory and excitatory neurotransmitters in the human brain, respectively, and their balanced interaction is necessary for neural function. Previous research suggests that the GABA and glutamate systems might be altered in autism. In this study, we used magnetic resonance spectroscopy to measure concentrations of these neurotransmitters in the sensory areas in the brains of young adults with autism. In contradiction to the common hypothesis of reduced GABA in autism, we demonstrate that concentrations of both GABA and glutamate, in all the brain regions examined, are comparable in individuals with autism and in neurotypical adults. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.2300 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=429

Could Sensory Differences Be a Sex-Indifferent Biomarker of Autism? Early Investigation Comparing Tactile Sensitivity Between Autistic Males and Females / Ericka L. WODKA ; Richard A.E. EDDEN ; Stewart H. MOSTOFSKY ; Nicolaas A.J. PUTS ; Jason L. HE in Journal of Autism and Developmental Disorders, 54-1 (January 2024)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 54-1 (January 2024) . - p.239-255 Titre : Could Sensory Differences Be a Sex-Indifferent Biomarker of Autism? Early Investigation Comparing Tactile Sensitivity Between Autistic Males and Females Type de document : texte imprimé Auteurs : Ericka L. WODKA, Auteur ; Richard A.E. EDDEN, Auteur ; Stewart H. MOSTOFSKY, Auteur ; Nicolaas A.J. PUTS, Auteur ; Jason L. HE, Auteur Article en page(s) : p.239-255 Index. décimale : PER Périodiques Résumé : Sensory differences are highly prevalent in autistic individuals. However, few studies have compared their presentation between autistic males and autistic females. We used psychophysics to assess and compare tactile perceptual sensitivity between autistic and non-autistic boys and girls aged between 8 and 12 years of age. While there were sex-differences of amplitude discrimination, frequency discrimination and order judgement thresholds, these sex-differences were not autism-specific. Mean RTs and detection thresholds were elevated in autism but were comparable between the sexes. Tactile sensitivity measures that are elevated in autism but are otherwise comparable between autistic males and autistic females suggest the possibility that certain sensory features could be used as sex-indifferent markers of autism. Further investigation with larger and more representative samples should be conducted before any stronger conclusions are made. En ligne : https://doi.org/10.1007/s10803-022-05787-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=520 [article] Could Sensory Differences Be a Sex-Indifferent Biomarker of Autism? Early Investigation Comparing Tactile Sensitivity Between Autistic Males and Females [texte imprimé] / Ericka L. WODKA, Auteur ; Richard A.E. EDDEN, Auteur ; Stewart H. MOSTOFSKY, Auteur ; Nicolaas A.J. PUTS, Auteur ; Jason L. HE, Auteur . - p.239-255. in Journal of Autism and Developmental Disorders > 54-1 (January 2024) . - p.239-255 Index. décimale : PER Périodiques Résumé : Sensory differences are highly prevalent in autistic individuals. However, few studies have compared their presentation between autistic males and autistic females. We used psychophysics to assess and compare tactile perceptual sensitivity between autistic and non-autistic boys and girls aged between 8 and 12 years of age. While there were sex-differences of amplitude discrimination, frequency discrimination and order judgement thresholds, these sex-differences were not autism-specific. Mean RTs and detection thresholds were elevated in autism but were comparable between the sexes. Tactile sensitivity measures that are elevated in autism but are otherwise comparable between autistic males and autistic females suggest the possibility that certain sensory features could be used as sex-indifferent markers of autism. Further investigation with larger and more representative samples should be conducted before any stronger conclusions are made. En ligne : https://doi.org/10.1007/s10803-022-05787-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=520

Perceptual alterations in the relationship between sensory reactivity, intolerance of uncertainty, and anxiety in autistic children with and without ADHD / Helen POWELL ; Jason L. HE ; Nermin KHALIL ; Ericka L. WODKA ; Alyssa DeRonda ; Richard A.E. EDDEN ; Roma A. VASA ; Stewart H. MOSTOFSKY ; Nicolaas A.J. PUTS in Development and Psychopathology, 37-1 (February 2025)  

Public ISBD [article]  inDevelopment and Psychopathology > 37-1 (February 2025) . - p.16-28 Titre : Perceptual alterations in the relationship between sensory reactivity, intolerance of uncertainty, and anxiety in autistic children with and without ADHD : Development and Psychopathology Type de document : texte imprimé Auteurs : Helen POWELL, Auteur ; Jason L. HE, Auteur ; Nermin KHALIL, Auteur ; Ericka L. WODKA, Auteur ; Alyssa DeRonda, Auteur ; Richard A.E. EDDEN, Auteur ; Roma A. VASA, Auteur ; Stewart H. MOSTOFSKY, Auteur ; Nicolaas A.J. PUTS, Auteur Article en page(s) : p.16-28 Langues : Anglais (eng) Mots-clés : anxiety  autism  intolerance of uncertainty  perception  sensory Index. décimale : PER Périodiques Résumé : Sensory differences and anxiety disorders are highly prevalent in autistic individuals with and without ADHD. Studies have shown that sensory differences and anxiety are associated and that intolerance of uncertainty (IU) plays an important role in this relationship. However, it is unclear as to how different levels of the sensory processing pathway (i.e., perceptual, affective, or behavioral) contribute. Here, we used psychophysics to assess how alterations in tactile perception contribute to questionnaire measures of sensory reactivity, IU, and anxiety. Thirty-eight autistic children (aged 8-12 years; 27 with co-occurring ADHD) were included. Consistent with previous findings, mediation analyses showed that child-reported IU fully mediated an association between parent-reported sensory reactivity and parent-reported anxiety and that anxiety partially mediated an association between sensory reactivity and IU. Of the vibrotactile thresholds, only simultaneous frequency discrimination (SFD) thresholds correlated with sensory reactivity. Interestingly, we found that sensory reactivity fully mediated an association between SFD threshold and anxiety, and between SFD threshold and IU. Taken together, those findings suggest a mechanistic pathway whereby tactile perceptual alterations contribute to sensory reactivity at the affective level, leading in turn to increased IU and anxiety. This stepwise association can inform potential interventions for IU and anxiety in autism. En ligne : https://dx.doi.org/10.1017/S0954579423001360 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=546 [article] Perceptual alterations in the relationship between sensory reactivity, intolerance of uncertainty, and anxiety in autistic children with and without ADHD : Development and Psychopathology [texte imprimé] / Helen POWELL, Auteur ; Jason L. HE, Auteur ; Nermin KHALIL, Auteur ; Ericka L. WODKA, Auteur ; Alyssa DeRonda, Auteur ; Richard A.E. EDDEN, Auteur ; Roma A. VASA, Auteur ; Stewart H. MOSTOFSKY, Auteur ; Nicolaas A.J. PUTS, Auteur . - p.16-28. Langues : Anglais (eng) in Development and Psychopathology > 37-1 (February 2025) . - p.16-28 Mots-clés : anxiety  autism  intolerance of uncertainty  perception  sensory Index. décimale : PER Périodiques Résumé : Sensory differences and anxiety disorders are highly prevalent in autistic individuals with and without ADHD. Studies have shown that sensory differences and anxiety are associated and that intolerance of uncertainty (IU) plays an important role in this relationship. However, it is unclear as to how different levels of the sensory processing pathway (i.e., perceptual, affective, or behavioral) contribute. Here, we used psychophysics to assess how alterations in tactile perception contribute to questionnaire measures of sensory reactivity, IU, and anxiety. Thirty-eight autistic children (aged 8-12 years; 27 with co-occurring ADHD) were included. Consistent with previous findings, mediation analyses showed that child-reported IU fully mediated an association between parent-reported sensory reactivity and parent-reported anxiety and that anxiety partially mediated an association between sensory reactivity and IU. Of the vibrotactile thresholds, only simultaneous frequency discrimination (SFD) thresholds correlated with sensory reactivity. Interestingly, we found that sensory reactivity fully mediated an association between SFD threshold and anxiety, and between SFD threshold and IU. Taken together, those findings suggest a mechanistic pathway whereby tactile perceptual alterations contribute to sensory reactivity at the affective level, leading in turn to increased IU and anxiety. This stepwise association can inform potential interventions for IU and anxiety in autism. En ligne : https://dx.doi.org/10.1017/S0954579423001360 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=546

Reduced GABA and altered somatosensory function in children with autism spectrum disorder / Nicolaas A.J. PUTS in Autism Research, 10-4 (April 2017)  

Public ISBD [article]  inAutism Research > 10-4 (April 2017) . - p.608-619 Titre : Reduced GABA and altered somatosensory function in children with autism spectrum disorder Type de document : texte imprimé Auteurs : Nicolaas A.J. PUTS, Auteur ; Ericka L. WODKA, Auteur ; Ashley D. HARRIS, Auteur ; Deana CROCETTI, Auteur ; Mark TOMMERDAHL, Auteur ; Stewart H. MOSTOFSKY, Auteur ; Richard A.E. EDDEN, Auteur Article en page(s) : p.608-619 Langues : Anglais (eng) Mots-clés : autism  somatosensory  GABA  magnetic resonance spectroscopy  tactile  MRS  touch Index. décimale : PER Périodiques Résumé : Background: Abnormal responses to tactile stimuli are a common feature of autism spectrum disorder (ASD). Several lines of evidence suggest that GABAergic function, which has a crucial role in tactile processing, is altered in ASD. In this study, we determine whether in vivo GABA levels are altered in children with ASD, and whether alterations in GABA levels are associated with abnormal tactile function in these children. Methods: GABA-edited magnetic resonance spectroscopy was acquired in 37 children with Autism and 35 typically developing children (TDC) from voxels over primary sensorimotor and occipital cortices. Children performed tactile tasks previously shown to be altered in ASD, linked to inhibitory mechanisms. Detection threshold was measured with- and without the presence of a slowly increasing sub-threshold stimulus. Amplitude discrimination was measured with- and without the presence of an adapting stimulus, and frequency discrimination was measured. Results: Sensorimotor GABA levels were significantly reduced in children with autism compared to healthy controls. Occipital GABA levels were normal. Sensorimotor GABA levels correlated with dynamic detection threshold as well as with the effect of sub-threshold stimulation. Sensorimotor GABA levels also correlated with amplitude discrimination after adaptation (an effect absent in autism) and frequency discrimination in controls, but not in children with autism. Conclusions: GABA levels correlate with behavioral measures of inhibition. Children with autism have reduced GABA, associated with abnormalities in tactile performance. We show here that altered in vivo GABA levels might predict abnormal tactile information processing in ASD and that the GABA system may be a future target for therapies. En ligne : http://dx.doi.org/10.1002/aur.1691 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=307 [article] Reduced GABA and altered somatosensory function in children with autism spectrum disorder [texte imprimé] / Nicolaas A.J. PUTS, Auteur ; Ericka L. WODKA, Auteur ; Ashley D. HARRIS, Auteur ; Deana CROCETTI, Auteur ; Mark TOMMERDAHL, Auteur ; Stewart H. MOSTOFSKY, Auteur ; Richard A.E. EDDEN, Auteur . - p.608-619. Langues : Anglais (eng) in Autism Research > 10-4 (April 2017) . - p.608-619 Mots-clés : autism  somatosensory  GABA  magnetic resonance spectroscopy  tactile  MRS  touch Index. décimale : PER Périodiques Résumé : Background: Abnormal responses to tactile stimuli are a common feature of autism spectrum disorder (ASD). Several lines of evidence suggest that GABAergic function, which has a crucial role in tactile processing, is altered in ASD. In this study, we determine whether in vivo GABA levels are altered in children with ASD, and whether alterations in GABA levels are associated with abnormal tactile function in these children. Methods: GABA-edited magnetic resonance spectroscopy was acquired in 37 children with Autism and 35 typically developing children (TDC) from voxels over primary sensorimotor and occipital cortices. Children performed tactile tasks previously shown to be altered in ASD, linked to inhibitory mechanisms. Detection threshold was measured with- and without the presence of a slowly increasing sub-threshold stimulus. Amplitude discrimination was measured with- and without the presence of an adapting stimulus, and frequency discrimination was measured. Results: Sensorimotor GABA levels were significantly reduced in children with autism compared to healthy controls. Occipital GABA levels were normal. Sensorimotor GABA levels correlated with dynamic detection threshold as well as with the effect of sub-threshold stimulation. Sensorimotor GABA levels also correlated with amplitude discrimination after adaptation (an effect absent in autism) and frequency discrimination in controls, but not in children with autism. Conclusions: GABA levels correlate with behavioral measures of inhibition. Children with autism have reduced GABA, associated with abnormalities in tactile performance. We show here that altered in vivo GABA levels might predict abnormal tactile information processing in ASD and that the GABA system may be a future target for therapies. En ligne : http://dx.doi.org/10.1002/aur.1691 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=307

The Role of Attention in Somatosensory Processing: A Multi-trait, Multi-method Analysis / Ericka L. WODKA in Journal of Autism and Developmental Disorders, 46-10 (October 2016)  

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