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

Increased prefrontal GABA concentrations in adults with autism spectrum disorders / Simon MAIER in Autism Research, 15-7 (July 2022)  

Public ISBD [article]  inAutism Research > 15-7 (July 2022) . - p.1222-1236 Titre : Increased prefrontal GABA concentrations in adults with autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : Simon MAIER, Auteur ; Ansgard Lena DÜPPERS, Auteur ; Kimon RUNGE, Auteur ; Michael DACKO, Auteur ; Thomas LANGE, Auteur ; Thomas FANGMEIER, Auteur ; Andreas RIEDEL, Auteur ; Dieter EBERT, Auteur ; Dominique ENDRES, Auteur ; Katharina DOMSCHKE, Auteur ; Evgeniy PERLOV, Auteur ; Kathrin NICKEL, Auteur ; Ludger TEBARTZ VAN ELST, Auteur Article en page(s) : p.1222-1236 Langues : Anglais (eng) Mots-clés : Gaba  anterior cingulate cortex  autism spectrum disorder  dorsolateral prefrontal cortex  gamma-aminobutyric acid  glutamate Index. décimale : PER Périodiques Résumé : The excitatory-inhibitory imbalance hypothesis postulates dysregulation of the gamma-aminobutyric acid (GABA) and glutamate (Glu) neurotransmitter systems as a common underlying deficit in individuals with autism spectrum disorders (ASD). Previous studies suggest an important role of these systems in the pathophysiology of ASD, including a study of our group reporting decreased glutamate concentrations in the pregenual anterior cingulate cortex (ACC) of adults with ASD. The aim of this study was to replicate our previous findings of impaired glutamate metabolism in ASD in a new sample and to additionally quantify GABA in the ACC and dorsolateral prefrontal cortex (dlPFC). Concentrations of GABA and glutamate-glutamine (Glx; combined glutamate and glutamine signal) were quantified in the ACC and dlPFC of 43 adults with ASD and 43 neurotypical controls (NTC) by magnetic resonance spectroscopy (MRS). The ASD group showed increased absolute GABA concentrations and elevated GABA/creatine ratios in the left dlPFC compared to NTC, while no group differences were detected in the pregenual and dorsal ACC. Previous findings of altered Glx concentration in the pregenual ACC of the ASD group could not be replicated. Regarding Glx concentrations and Glx/creatine ratios, there were no significant differences in the dlPFC and ACC either. The study supports the hypothesis of an altered GABA and glutamate equilibrium, indicating an imbalance between excitatory and inhibitory metabolism in ASD patients. However, inconsistent results across studies and brain regions suggest a complex underlying phenomenon. LAY SUMMARY: Adults of the autism spectrum exhibit elevated levels of the inhibitory neurotransmitter GABA in the left dorsolateral prefrontal cortex. This finding supports the hypothesis of an imbalance between excitatory and inhibitory equilibrium in patients with autism spectrum disorders. En ligne : http://dx.doi.org/10.1002/aur.2740 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=476 [article] Increased prefrontal GABA concentrations in adults with autism spectrum disorders [Texte imprimé et/ou numérique] / Simon MAIER, Auteur ; Ansgard Lena DÜPPERS, Auteur ; Kimon RUNGE, Auteur ; Michael DACKO, Auteur ; Thomas LANGE, Auteur ; Thomas FANGMEIER, Auteur ; Andreas RIEDEL, Auteur ; Dieter EBERT, Auteur ; Dominique ENDRES, Auteur ; Katharina DOMSCHKE, Auteur ; Evgeniy PERLOV, Auteur ; Kathrin NICKEL, Auteur ; Ludger TEBARTZ VAN ELST, Auteur . - p.1222-1236. Langues : Anglais (eng) in Autism Research > 15-7 (July 2022) . - p.1222-1236 Mots-clés : Gaba  anterior cingulate cortex  autism spectrum disorder  dorsolateral prefrontal cortex  gamma-aminobutyric acid  glutamate Index. décimale : PER Périodiques Résumé : The excitatory-inhibitory imbalance hypothesis postulates dysregulation of the gamma-aminobutyric acid (GABA) and glutamate (Glu) neurotransmitter systems as a common underlying deficit in individuals with autism spectrum disorders (ASD). Previous studies suggest an important role of these systems in the pathophysiology of ASD, including a study of our group reporting decreased glutamate concentrations in the pregenual anterior cingulate cortex (ACC) of adults with ASD. The aim of this study was to replicate our previous findings of impaired glutamate metabolism in ASD in a new sample and to additionally quantify GABA in the ACC and dorsolateral prefrontal cortex (dlPFC). Concentrations of GABA and glutamate-glutamine (Glx; combined glutamate and glutamine signal) were quantified in the ACC and dlPFC of 43 adults with ASD and 43 neurotypical controls (NTC) by magnetic resonance spectroscopy (MRS). The ASD group showed increased absolute GABA concentrations and elevated GABA/creatine ratios in the left dlPFC compared to NTC, while no group differences were detected in the pregenual and dorsal ACC. Previous findings of altered Glx concentration in the pregenual ACC of the ASD group could not be replicated. Regarding Glx concentrations and Glx/creatine ratios, there were no significant differences in the dlPFC and ACC either. The study supports the hypothesis of an altered GABA and glutamate equilibrium, indicating an imbalance between excitatory and inhibitory metabolism in ASD patients. However, inconsistent results across studies and brain regions suggest a complex underlying phenomenon. LAY SUMMARY: Adults of the autism spectrum exhibit elevated levels of the inhibitory neurotransmitter GABA in the left dorsolateral prefrontal cortex. This finding supports the hypothesis of an imbalance between excitatory and inhibitory equilibrium in patients with autism spectrum disorders. En ligne : http://dx.doi.org/10.1002/aur.2740 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=476

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