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 et/ou numérique 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 et/ou numérique] / 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

Increased cerebral lactate levels in adults with autism spectrum disorders compared to non-autistic controls: a magnetic resonance spectroscopy study / Kathrin NICKEL ; Thomas LANGE ; Georg OELTZSCHNER ; Michael DACKO ; Dominique ENDRES ; Kimon RUNGE ; Anke SCHUMANN ; Katharina DOMSCHKE ; Michalis ROUSOS ; Ludger TEBARTZ VAN ELST in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 44 p. Titre : Increased cerebral lactate levels in adults with autism spectrum disorders compared to non-autistic controls: a magnetic resonance spectroscopy study Type de document : Texte imprimé et/ou numérique Auteurs : Kathrin NICKEL, Auteur ; Thomas LANGE, Auteur ; Georg OELTZSCHNER, Auteur ; Michael DACKO, Auteur ; Dominique ENDRES, Auteur ; Kimon RUNGE, Auteur ; Anke SCHUMANN, Auteur ; Katharina DOMSCHKE, Auteur ; Michalis ROUSOS, Auteur ; Ludger TEBARTZ VAN ELST, Auteur Article en page(s) : 44 p. Langues : Anglais (eng) Mots-clés : Humans  Adult  *Autism Spectrum Disorder/diagnostic imaging/metabolism  Magnetic Resonance Spectroscopy/methods  Magnetic Resonance Imaging  Lactic Acid/metabolism  Biomarkers  Autism spectrum disorder  Lactate  Magnetic resonance spectroscopy  Mitochondria  Mitochondrial dysfunction  Posterior cingulate cortex  or travel grants within the last 3 years: Roche, Eli Lilly, Janssen-Cilag,  Novartis, Shire, UCB, GSK, Servier, Janssen, and Cyberonics. All other authors  declare that they do not have any conflicts of interest. Index. décimale : PER Périodiques Résumé : INTRODUCTION: Autism spectrum disorder (ASD) encompasses a heterogeneous group with varied phenotypes and etiologies. Identifying pathogenic subgroups could facilitate targeted treatments. One promising avenue is investigating energy metabolism, as mitochondrial dysfunction has been implicated in a subgroup of ASD. Lactate, an indicator of energy metabolic anomalies, may serve as a potential biomarker for this subgroup. This study aimed to examine cerebral lactate (Lac+) levels in high-functioning adults with ASD, hypothesizing elevated mean Lac+ concentrations in contrast to neurotypical controls (NTCs). MATERIALS AND METHODS: Magnetic resonance spectroscopy (MRS) was used to study cerebral Lac+ in 71 adults with ASD and NTC, focusing on the posterior cingulate cortex (PCC). After quality control, 64 ASD and 58 NTC participants remained. Lac+ levels two standard deviations above the mean of the control group were considered elevated. RESULTS: Mean PCC Lac+ levels were significantly higher in the ASD group than in the NTC group (p=0.028; Cohen's d=0.404), and 9.4% of the ASD group had elevated levels as compared to 0% of the NTCs (p=0.029). No significant correlation was found between blood serum lactate levels and MRS-derived Lac+ levels. LIMITATIONS: A cautious interpretation of our results is warranted due to a p value of 0.028. In addition, a higher than anticipated proportion of data sets had to be excluded due to poor spectral quality. CONCLUSION: This study confirms the presence of elevated cerebral Lac+ levels in a subgroup of adults with ASD, suggesting the potential of lactate as a biomarker for mitochondrial dysfunction in a subgroup of ASD. The lower-than-expected prevalence (20% was expected) and moderate increase require further investigation to elucidate the underlying mechanisms and relationships with mitochondrial function. En ligne : https://dx.doi.org/10.1186/s13229-023-00577-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=518 [article] Increased cerebral lactate levels in adults with autism spectrum disorders compared to non-autistic controls: a magnetic resonance spectroscopy study [Texte imprimé et/ou numérique] / Kathrin NICKEL, Auteur ; Thomas LANGE, Auteur ; Georg OELTZSCHNER, Auteur ; Michael DACKO, Auteur ; Dominique ENDRES, Auteur ; Kimon RUNGE, Auteur ; Anke SCHUMANN, Auteur ; Katharina DOMSCHKE, Auteur ; Michalis ROUSOS, Auteur ; Ludger TEBARTZ VAN ELST, Auteur . - 44 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 44 p. Mots-clés : Humans  Adult  *Autism Spectrum Disorder/diagnostic imaging/metabolism  Magnetic Resonance Spectroscopy/methods  Magnetic Resonance Imaging  Lactic Acid/metabolism  Biomarkers  Autism spectrum disorder  Lactate  Magnetic resonance spectroscopy  Mitochondria  Mitochondrial dysfunction  Posterior cingulate cortex  or travel grants within the last 3 years: Roche, Eli Lilly, Janssen-Cilag,  Novartis, Shire, UCB, GSK, Servier, Janssen, and Cyberonics. All other authors  declare that they do not have any conflicts of interest. Index. décimale : PER Périodiques Résumé : INTRODUCTION: Autism spectrum disorder (ASD) encompasses a heterogeneous group with varied phenotypes and etiologies. Identifying pathogenic subgroups could facilitate targeted treatments. One promising avenue is investigating energy metabolism, as mitochondrial dysfunction has been implicated in a subgroup of ASD. Lactate, an indicator of energy metabolic anomalies, may serve as a potential biomarker for this subgroup. This study aimed to examine cerebral lactate (Lac+) levels in high-functioning adults with ASD, hypothesizing elevated mean Lac+ concentrations in contrast to neurotypical controls (NTCs). MATERIALS AND METHODS: Magnetic resonance spectroscopy (MRS) was used to study cerebral Lac+ in 71 adults with ASD and NTC, focusing on the posterior cingulate cortex (PCC). After quality control, 64 ASD and 58 NTC participants remained. Lac+ levels two standard deviations above the mean of the control group were considered elevated. RESULTS: Mean PCC Lac+ levels were significantly higher in the ASD group than in the NTC group (p=0.028; Cohen's d=0.404), and 9.4% of the ASD group had elevated levels as compared to 0% of the NTCs (p=0.029). No significant correlation was found between blood serum lactate levels and MRS-derived Lac+ levels. LIMITATIONS: A cautious interpretation of our results is warranted due to a p value of 0.028. In addition, a higher than anticipated proportion of data sets had to be excluded due to poor spectral quality. CONCLUSION: This study confirms the presence of elevated cerebral Lac+ levels in a subgroup of adults with ASD, suggesting the potential of lactate as a biomarker for mitochondrial dysfunction in a subgroup of ASD. The lower-than-expected prevalence (20% was expected) and moderate increase require further investigation to elucidate the underlying mechanisms and relationships with mitochondrial function. En ligne : https://dx.doi.org/10.1186/s13229-023-00577-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=518

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