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Glutathione metabolism in the prefrontal brain of adults with high-functioning autism spectrum disorder: an MRS study / D. ENDRES in Molecular Autism, 8 (2017)
[article]
Titre : Glutathione metabolism in the prefrontal brain of adults with high-functioning autism spectrum disorder: an MRS study Type de document : Texte imprimé et/ou numérique Auteurs : D. ENDRES, Auteur ; L. TEBARTZ VAN ELST, Auteur ; S. A. MEYER, Auteur ; B. FEIGE, Auteur ; K. NICKEL, Auteur ; A. BUBL, Auteur ; A. RIEDEL, Auteur ; D. EBERT, Auteur ; T. LANGE, Auteur ; V. GLAUCHE, Auteur ; Monica BISCALDI, Auteur ; A. PHILIPSEN, Auteur ; S. J. MAIER, Auteur ; E. PERLOV, Auteur Article en page(s) : 10p. Langues : Anglais (eng) Mots-clés : Adult Autism Spectrum Disorder/metabolism/*psychology Female Glutathione/*metabolism Humans Male Middle Aged Prefrontal Cortex/*metabolism Proton Magnetic Resonance Spectroscopy/*methods *Anterior cingulate cortex *Asperger syndrome *Autism spectrum disorder *Dlpfc *Glutathione *MR spectroscopy Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disease characterized by difficulties in social communication, unusually restricted, repetitive behavior and interests, and specific abnormalities in language and perception. The precise etiology of ASD is still unknown and probably heterogeneous. In a subgroup of patients, toxic environmental exposure might lead to an imbalance between oxidative stress and anti-oxidant systems. Previous serum and postmortem studies measuring levels of glutathione (GSH), the main cellular free radical scavenger in the brain, have supported the hypothesis that this compound might play a role in the pathophysiology of autism. METHODS: Using the method of single-voxel proton magnetic resonance spectroscopy (MRS), we analyzed the GSH signal in the dorsal anterior cingulate cortex (dACC) and the dorsolateral prefrontal cortex (DLPFC) of 24 ASD patients with normal or above average IQs and 18 matched control subjects. We hypothesized that we would find decreased GSH concentrations in both regions. RESULTS: We did not find overall group differences in neurometabolites including GSH, neither in the dorsal ACC (Wilks' lambda test; p = 0.429) nor in the DLPFC (p = 0.288). In the dACC, we found a trend for decreased GSH signals in ASD patients (p = 0.076). CONCLUSIONS: We were unable to confirm our working hypothesis regarding decreased GSH concentrations in the ASD group. Further studies combining MRS, serum, and cerebrospinal fluid measurements of GSH metabolism including other regions of interest or even whole brain spectroscopy are needed. En ligne : http://dx.doi.org/10.1186/s13229-017-0122-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330
in Molecular Autism > 8 (2017) . - 10p.[article] Glutathione metabolism in the prefrontal brain of adults with high-functioning autism spectrum disorder: an MRS study [Texte imprimé et/ou numérique] / D. ENDRES, Auteur ; L. TEBARTZ VAN ELST, Auteur ; S. A. MEYER, Auteur ; B. FEIGE, Auteur ; K. NICKEL, Auteur ; A. BUBL, Auteur ; A. RIEDEL, Auteur ; D. EBERT, Auteur ; T. LANGE, Auteur ; V. GLAUCHE, Auteur ; Monica BISCALDI, Auteur ; A. PHILIPSEN, Auteur ; S. J. MAIER, Auteur ; E. PERLOV, Auteur . - 10p.
Langues : Anglais (eng)
in Molecular Autism > 8 (2017) . - 10p.
Mots-clés : Adult Autism Spectrum Disorder/metabolism/*psychology Female Glutathione/*metabolism Humans Male Middle Aged Prefrontal Cortex/*metabolism Proton Magnetic Resonance Spectroscopy/*methods *Anterior cingulate cortex *Asperger syndrome *Autism spectrum disorder *Dlpfc *Glutathione *MR spectroscopy Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disease characterized by difficulties in social communication, unusually restricted, repetitive behavior and interests, and specific abnormalities in language and perception. The precise etiology of ASD is still unknown and probably heterogeneous. In a subgroup of patients, toxic environmental exposure might lead to an imbalance between oxidative stress and anti-oxidant systems. Previous serum and postmortem studies measuring levels of glutathione (GSH), the main cellular free radical scavenger in the brain, have supported the hypothesis that this compound might play a role in the pathophysiology of autism. METHODS: Using the method of single-voxel proton magnetic resonance spectroscopy (MRS), we analyzed the GSH signal in the dorsal anterior cingulate cortex (dACC) and the dorsolateral prefrontal cortex (DLPFC) of 24 ASD patients with normal or above average IQs and 18 matched control subjects. We hypothesized that we would find decreased GSH concentrations in both regions. RESULTS: We did not find overall group differences in neurometabolites including GSH, neither in the dorsal ACC (Wilks' lambda test; p = 0.429) nor in the DLPFC (p = 0.288). In the dACC, we found a trend for decreased GSH signals in ASD patients (p = 0.076). CONCLUSIONS: We were unable to confirm our working hypothesis regarding decreased GSH concentrations in the ASD group. Further studies combining MRS, serum, and cerebrospinal fluid measurements of GSH metabolism including other regions of interest or even whole brain spectroscopy are needed. En ligne : http://dx.doi.org/10.1186/s13229-017-0122-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330 Umbilical cord blood androgen levels and ASD-related phenotypes at 12 and 36 months in an enriched risk cohort study / B. Y. PARK in Molecular Autism, 8 (2017)
[article]
Titre : Umbilical cord blood androgen levels and ASD-related phenotypes at 12 and 36 months in an enriched risk cohort study Type de document : Texte imprimé et/ou numérique Auteurs : B. Y. PARK, Auteur ; Brian K. LEE, Auteur ; Igor BURSTYN, Auteur ; Loni P. TABB, Auteur ; J. A. KEELAN, Auteur ; Andrew J. O. WHITEHOUSE, Auteur ; Lisa A. CROEN, Auteur ; M. D. FALLIN, Auteur ; I. HERTZ-PICCIOTTO, Auteur ; O. MONTGOMERY, Auteur ; C. J. NEWSCHAFFER, Auteur Article en page(s) : 3p. Langues : Anglais (eng) Mots-clés : Adult Androstenedione/*metabolism Autism Spectrum Disorder/metabolism/*psychology Chromatography, Liquid Cohort Studies Dehydroepiandrosterone/*metabolism Female Fetal Blood/*metabolism Humans Infant Linear Models Longitudinal Studies Male Pregnancy Prospective Studies Risk Assessment Severity of Illness Index Siblings/*psychology Tandem Mass Spectrometry Testosterone/*metabolism *Autism *Sex difference *Sibling *Testosterone *Umbilical cord blood Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) affects more than 1% of children in the USA. The male-to-female prevalence ratio of roughly 4:1 in ASD is a well-recognized but poorly understood phenomenon. An explicit focus on potential etiologic pathways consistent with this sex difference, such as those involving prenatal androgen exposure, may help elucidate causes of ASD. Furthermore, the multi-threshold liability model suggests that the genetic mechanisms in females with ASD may be distinct and may modulate ASD risk in families with female ASD in the pedigree. METHODS: We examined umbilical cord blood from 137 children in the Early Autism Risk Longitudinal Investigation (EARLI) cohort. EARLI is an ASD-enriched risk cohort with all children having an older sibling already diagnosed with ASD. Fetal testosterone (T), androstenedione (A4), and dehyroepiandrosterone (DHEA) levels were measured in cord blood using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Robust linear regression models were used to determine associations between cord blood androgen levels and 12-month Autism Observation Scales for Infants (AOSI) scores and 36-month Social Responsiveness Scale (SRS) scores adjusting for potential confounders. RESULTS: Increasing androgens were not associated with increasing 12-month AOSI score or 36-month total SRS score in either boys or girls. However, the association between T and autistic traits among subjects with a female older affected sibling was greater at 12 months (test of interaction, P = 0.008) and deficits in reciprocal social behavior at 36 months were also greater (test of interaction, P = 0.006) than in subjects whose older affected sibling was male. CONCLUSIONS: While increased prenatal testosterone levels were not associated with autistic traits at 12 or 36 months, our findings of a positive association in infants whose older ASD-affected siblings were female suggests an androgen-related mechanism that may be dependent on, or related to, genetic liability factors present more often in families containing female ASD cases. However, this initial finding, based on a small subgroup of our sample, should be interpreted with considerable caution. En ligne : http://dx.doi.org/10.1186/s13229-017-0118-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330
in Molecular Autism > 8 (2017) . - 3p.[article] Umbilical cord blood androgen levels and ASD-related phenotypes at 12 and 36 months in an enriched risk cohort study [Texte imprimé et/ou numérique] / B. Y. PARK, Auteur ; Brian K. LEE, Auteur ; Igor BURSTYN, Auteur ; Loni P. TABB, Auteur ; J. A. KEELAN, Auteur ; Andrew J. O. WHITEHOUSE, Auteur ; Lisa A. CROEN, Auteur ; M. D. FALLIN, Auteur ; I. HERTZ-PICCIOTTO, Auteur ; O. MONTGOMERY, Auteur ; C. J. NEWSCHAFFER, Auteur . - 3p.
Langues : Anglais (eng)
in Molecular Autism > 8 (2017) . - 3p.
Mots-clés : Adult Androstenedione/*metabolism Autism Spectrum Disorder/metabolism/*psychology Chromatography, Liquid Cohort Studies Dehydroepiandrosterone/*metabolism Female Fetal Blood/*metabolism Humans Infant Linear Models Longitudinal Studies Male Pregnancy Prospective Studies Risk Assessment Severity of Illness Index Siblings/*psychology Tandem Mass Spectrometry Testosterone/*metabolism *Autism *Sex difference *Sibling *Testosterone *Umbilical cord blood Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) affects more than 1% of children in the USA. The male-to-female prevalence ratio of roughly 4:1 in ASD is a well-recognized but poorly understood phenomenon. An explicit focus on potential etiologic pathways consistent with this sex difference, such as those involving prenatal androgen exposure, may help elucidate causes of ASD. Furthermore, the multi-threshold liability model suggests that the genetic mechanisms in females with ASD may be distinct and may modulate ASD risk in families with female ASD in the pedigree. METHODS: We examined umbilical cord blood from 137 children in the Early Autism Risk Longitudinal Investigation (EARLI) cohort. EARLI is an ASD-enriched risk cohort with all children having an older sibling already diagnosed with ASD. Fetal testosterone (T), androstenedione (A4), and dehyroepiandrosterone (DHEA) levels were measured in cord blood using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Robust linear regression models were used to determine associations between cord blood androgen levels and 12-month Autism Observation Scales for Infants (AOSI) scores and 36-month Social Responsiveness Scale (SRS) scores adjusting for potential confounders. RESULTS: Increasing androgens were not associated with increasing 12-month AOSI score or 36-month total SRS score in either boys or girls. However, the association between T and autistic traits among subjects with a female older affected sibling was greater at 12 months (test of interaction, P = 0.008) and deficits in reciprocal social behavior at 36 months were also greater (test of interaction, P = 0.006) than in subjects whose older affected sibling was male. CONCLUSIONS: While increased prenatal testosterone levels were not associated with autistic traits at 12 or 36 months, our findings of a positive association in infants whose older ASD-affected siblings were female suggests an androgen-related mechanism that may be dependent on, or related to, genetic liability factors present more often in families containing female ASD cases. However, this initial finding, based on a small subgroup of our sample, should be interpreted with considerable caution. En ligne : http://dx.doi.org/10.1186/s13229-017-0118-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330