Altered markers of mitochondrial function in adults with autism spectrum disorder / Mia MENKE ; Dominique ENDRES ; Kimon RUNGE ; Sara TUCCI ; Anke SCHUMANN ; Katharina DOMSCHKE ; Ludger TEBARTZ VAN ELST ; Simon MAIER in Autism Research, 16-11 (November 2023)  

Public ISBD [article]  inAutism Research > 16-11 (November 2023) . - p.2125-2138 Titre : Altered markers of mitochondrial function in adults with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Mia MENKE, Auteur ; Dominique ENDRES, Auteur ; Kimon RUNGE, Auteur ; Sara TUCCI, Auteur ; Anke SCHUMANN, Auteur ; Katharina DOMSCHKE, Auteur ; Ludger TEBARTZ VAN ELST, Auteur ; Simon MAIER, Auteur Article en page(s) : p.2125-2138 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Abstract Previous research suggests potential mitochondrial dysfunction and changes in fatty acid metabolism in a subgroup of individuals with autism spectrum disorder (ASD), indicated by higher lactate, pyruvate levels, and mitochondrial disorder prevalence. This study aimed to further investigate potential mitochondrial dysfunction in ASD by assessing blood metabolite levels linked to mitochondrial metabolism. Blood levels of creatine kinase (CK), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate, pyruvate, free and total carnitine, as well as acylcarnitines were obtained in 73 adults with ASD (47 males, 26 females) and compared with those of 71 neurotypical controls (NTC) (44 males, 27 females). Correlations between blood parameters and psychometric ASD symptom scores were also explored. Lower CK (pcorr=0.045) levels were found exclusively in males with ASD compared to NTC, with no such variation in females. ALT and AST levels did not differ significantly between both groups. After correction for antipsychotic and antidepressant medication, CK remained significant. ASD participants had lower serum lactate levels (pcorr=0.036) compared to NTC, but pyruvate and carnitine concentrations showed no significant difference. ASD subjects had significantly increased levels of certain acylcarnitines, with a decrease in tetradecadienoyl-carnitine (C14:2), and certain acylcarnitines correlated significantly with autistic symptom scores. We found reduced serum lactate levels in ASD, in contrast to previous studies suggesting elevated lactate or pyruvate. This difference may reflect the focus of our study on high-functioning adults with ASD, who are likely to have fewer secondary genetic conditions associated with mitochondrial dysfunction. Our findings of significantly altered acylcarnitine levels in ASD support the hypothesis of altered fatty acid metabolism in a subset of ASD patients. En ligne : https://doi.org/10.1002/aur.3029 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=517 [article] Altered markers of mitochondrial function in adults with autism spectrum disorder [Texte imprimé et/ou numérique] / Mia MENKE, Auteur ; Dominique ENDRES, Auteur ; Kimon RUNGE, Auteur ; Sara TUCCI, Auteur ; Anke SCHUMANN, Auteur ; Katharina DOMSCHKE, Auteur ; Ludger TEBARTZ VAN ELST, Auteur ; Simon MAIER, Auteur . - p.2125-2138. Langues : Anglais (eng) in Autism Research > 16-11 (November 2023) . - p.2125-2138 Index. décimale : PER Périodiques Résumé : Abstract Previous research suggests potential mitochondrial dysfunction and changes in fatty acid metabolism in a subgroup of individuals with autism spectrum disorder (ASD), indicated by higher lactate, pyruvate levels, and mitochondrial disorder prevalence. This study aimed to further investigate potential mitochondrial dysfunction in ASD by assessing blood metabolite levels linked to mitochondrial metabolism. Blood levels of creatine kinase (CK), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate, pyruvate, free and total carnitine, as well as acylcarnitines were obtained in 73 adults with ASD (47 males, 26 females) and compared with those of 71 neurotypical controls (NTC) (44 males, 27 females). Correlations between blood parameters and psychometric ASD symptom scores were also explored. Lower CK (pcorr=0.045) levels were found exclusively in males with ASD compared to NTC, with no such variation in females. ALT and AST levels did not differ significantly between both groups. After correction for antipsychotic and antidepressant medication, CK remained significant. ASD participants had lower serum lactate levels (pcorr=0.036) compared to NTC, but pyruvate and carnitine concentrations showed no significant difference. ASD subjects had significantly increased levels of certain acylcarnitines, with a decrease in tetradecadienoyl-carnitine (C14:2), and certain acylcarnitines correlated significantly with autistic symptom scores. We found reduced serum lactate levels in ASD, in contrast to previous studies suggesting elevated lactate or pyruvate. This difference may reflect the focus of our study on high-functioning adults with ASD, who are likely to have fewer secondary genetic conditions associated with mitochondrial dysfunction. Our findings of significantly altered acylcarnitine levels in ASD support the hypothesis of altered fatty acid metabolism in a subset of ASD patients. En ligne : https://doi.org/10.1002/aur.3029 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=517

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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