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Age-related parietal GABA alterations in children with autism spectrum disorder / Marilena M. DEMAYO in Autism Research, 14-5 (May 2021)
[article]
Titre : Age-related parietal GABA alterations in children with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Marilena M. DEMAYO, Auteur ; Ashley D. HARRIS, Auteur ; Yun Ju C. SONG, Auteur ; Izabella POKORSKI, Auteur ; Rinku THAPA, Auteur ; Shrujna PATEL, Auteur ; Zahava AMBARCHI, Auteur ; Emma E. THOMAS, Auteur ; Ian B. HICKIE, Auteur ; Adam J. GUASTELLA, Auteur Article en page(s) : p.859-872 Langues : Anglais (eng) Mots-clés : GABA (gamma-aminobutyric acid) biomarker children magnetic resonance spectroscopy (MRS) neurochemistry parietal lobe Index. décimale : PER Périodiques Résumé : GABA is the primary inhibitory neurotransmitter in the brain, and is essential to the balance of cortical excitation and inhibition. Reductions in GABA are proposed to result in an overly excitatory cortex that may cause, or contribute to, symptoms of autism spectrum disorder (ASD). This study employed a cross-sectional design to explore GABA+ differences in ASD and the impact of age, comparing 4-12?year olds with ASD (N = 24) to typically developing children (N = 35). GABA+ concentration was measured using edited magnetic resonance spectroscopy in the left parietal lobe. This study used a mixed model to investigate group differences between children with ASD and typically developing children. There was a significant difference in GABA+ levels between the groups, a significant effect of age and interaction between age and diagnostic group. The ASD group showed an association between GABA+ and age, with GABA+ levels gradually increasing with age (r = 0.59, p = 0.003). Typically developing children did not show age-related change in GABA+ concentration (r = 0.09, p?= 0.60). By the age of 9, children with ASD showed GABA+ levels that were comparable to their typically developing peers. This study suggests that children with ASD have initially lower levels of GABA+ in the left parietal lobe compared to typically developing children, and that these initially lower levels of GABA+ increase with age in ASD within this region. It is suggested that this developmental shift of GABA+ levels within the left parietal lobe provides a possible explanation for the previously found reductions in childhood that does not persist in adults. LAY SUMMARY: This study measured levels of GABA in the left parietal lobe using magnetic resonance spectroscopy in children with ASD and typically developing children. GABA levels were initially lower in the ASD group, and increased with age, while GABA did not change with age in the typically developing group. This suggests that alterations in GABA signaling may be associated with ASD in childhood. Autism Res 2021, 14: 859-872. © 2021 International Society for Autism Research, Wiley Periodicals LLC. En ligne : http://dx.doi.org/10.1002/aur.2487 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=444
in Autism Research > 14-5 (May 2021) . - p.859-872[article] Age-related parietal GABA alterations in children with autism spectrum disorder [Texte imprimé et/ou numérique] / Marilena M. DEMAYO, Auteur ; Ashley D. HARRIS, Auteur ; Yun Ju C. SONG, Auteur ; Izabella POKORSKI, Auteur ; Rinku THAPA, Auteur ; Shrujna PATEL, Auteur ; Zahava AMBARCHI, Auteur ; Emma E. THOMAS, Auteur ; Ian B. HICKIE, Auteur ; Adam J. GUASTELLA, Auteur . - p.859-872.
Langues : Anglais (eng)
in Autism Research > 14-5 (May 2021) . - p.859-872
Mots-clés : GABA (gamma-aminobutyric acid) biomarker children magnetic resonance spectroscopy (MRS) neurochemistry parietal lobe Index. décimale : PER Périodiques Résumé : GABA is the primary inhibitory neurotransmitter in the brain, and is essential to the balance of cortical excitation and inhibition. Reductions in GABA are proposed to result in an overly excitatory cortex that may cause, or contribute to, symptoms of autism spectrum disorder (ASD). This study employed a cross-sectional design to explore GABA+ differences in ASD and the impact of age, comparing 4-12?year olds with ASD (N = 24) to typically developing children (N = 35). GABA+ concentration was measured using edited magnetic resonance spectroscopy in the left parietal lobe. This study used a mixed model to investigate group differences between children with ASD and typically developing children. There was a significant difference in GABA+ levels between the groups, a significant effect of age and interaction between age and diagnostic group. The ASD group showed an association between GABA+ and age, with GABA+ levels gradually increasing with age (r = 0.59, p = 0.003). Typically developing children did not show age-related change in GABA+ concentration (r = 0.09, p?= 0.60). By the age of 9, children with ASD showed GABA+ levels that were comparable to their typically developing peers. This study suggests that children with ASD have initially lower levels of GABA+ in the left parietal lobe compared to typically developing children, and that these initially lower levels of GABA+ increase with age in ASD within this region. It is suggested that this developmental shift of GABA+ levels within the left parietal lobe provides a possible explanation for the previously found reductions in childhood that does not persist in adults. LAY SUMMARY: This study measured levels of GABA in the left parietal lobe using magnetic resonance spectroscopy in children with ASD and typically developing children. GABA levels were initially lower in the ASD group, and increased with age, while GABA did not change with age in the typically developing group. This suggests that alterations in GABA signaling may be associated with ASD in childhood. Autism Res 2021, 14: 859-872. © 2021 International Society for Autism Research, Wiley Periodicals LLC. En ligne : http://dx.doi.org/10.1002/aur.2487 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=444 TPH2 G/T polymorphism is associated with hyperphagia, IQ, and internalizing problems in Prader–Willi syndrome / Elisabeth M. DYKENS in Journal of Child Psychology and Psychiatry, 52-5 (May 2011)
[article]
Titre : TPH2 G/T polymorphism is associated with hyperphagia, IQ, and internalizing problems in Prader–Willi syndrome Type de document : Texte imprimé et/ou numérique Auteurs : Elisabeth M. DYKENS, Auteur ; Elizabeth ROOF, Auteur ; Douglas BITTEL, Auteur ; Merlin G. BUTLER, Auteur Année de publication : 2011 Article en page(s) : p.580-587 Langues : Anglais (eng) Mots-clés : Behavior problems genetics intelligence internalizing disorder neurochemistry Prader–Willi syndrome Index. décimale : PER Périodiques Résumé : Background: Prader–Willi syndrome (PWS) is a genetic, neurodevelopmental disorder characterized by intellectual disabilities, growth hormone dysregulation, hyperphagia, increased risks of morbid obesity, compulsive behaviors, and irritability. As aberrant serotonergic functioning is strongly implicated in PWS, we examined associations between the PWS phenotype and polymorphisms in tryptophan hydroxylase 2 (TPH2), the rate-limiting enzyme in the biosynthesis of serotonin in the brain.
Methods: Ninety-two individuals with PWS aged 4 to 50 years (M = 21.97) were genotyped for the TPH2 G703-T polymorphism. IQ testing was conducted in offspring, and parents completed questionnaires that tapped their child’s compulsivity, hyperphagia, and other behavior problems.
Results: As expected, the frequency of G/T or T/T polymorphisms in participants with PWS (39%) was similar to rates found in the general population (38%). Compared to those with a homozygous (G/G) genotype, individuals with a T allele had significantly higher hyperphagic behavior, drive, and severity scores, and they also had a younger age of onset of hyperphagia. Those with a T allele also had higher IQ scores than their counterparts. Females with a T allele had significantly higher internalizing symptoms, primarily anxiety and depression, than all others.
Conclusions: TPH2 G/T polymorphisms, and presumed loss of enzyme function, were associated with specific aspects of the PWS phenotype. Aberrant serotonergic functioning is strongly implicated in hyperphagia in PWS, and females with TPH2 T alleles may be at higher risk for affective or mood disorders. Findings hold promise for examining other serotonin-altering genes in PWS, and for future serotonin-altering treatment trials.En ligne : http://dx.doi.org/10.1111/j.1469-7610.2011.02365.x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=121
in Journal of Child Psychology and Psychiatry > 52-5 (May 2011) . - p.580-587[article] TPH2 G/T polymorphism is associated with hyperphagia, IQ, and internalizing problems in Prader–Willi syndrome [Texte imprimé et/ou numérique] / Elisabeth M. DYKENS, Auteur ; Elizabeth ROOF, Auteur ; Douglas BITTEL, Auteur ; Merlin G. BUTLER, Auteur . - 2011 . - p.580-587.
Langues : Anglais (eng)
in Journal of Child Psychology and Psychiatry > 52-5 (May 2011) . - p.580-587
Mots-clés : Behavior problems genetics intelligence internalizing disorder neurochemistry Prader–Willi syndrome Index. décimale : PER Périodiques Résumé : Background: Prader–Willi syndrome (PWS) is a genetic, neurodevelopmental disorder characterized by intellectual disabilities, growth hormone dysregulation, hyperphagia, increased risks of morbid obesity, compulsive behaviors, and irritability. As aberrant serotonergic functioning is strongly implicated in PWS, we examined associations between the PWS phenotype and polymorphisms in tryptophan hydroxylase 2 (TPH2), the rate-limiting enzyme in the biosynthesis of serotonin in the brain.
Methods: Ninety-two individuals with PWS aged 4 to 50 years (M = 21.97) were genotyped for the TPH2 G703-T polymorphism. IQ testing was conducted in offspring, and parents completed questionnaires that tapped their child’s compulsivity, hyperphagia, and other behavior problems.
Results: As expected, the frequency of G/T or T/T polymorphisms in participants with PWS (39%) was similar to rates found in the general population (38%). Compared to those with a homozygous (G/G) genotype, individuals with a T allele had significantly higher hyperphagic behavior, drive, and severity scores, and they also had a younger age of onset of hyperphagia. Those with a T allele also had higher IQ scores than their counterparts. Females with a T allele had significantly higher internalizing symptoms, primarily anxiety and depression, than all others.
Conclusions: TPH2 G/T polymorphisms, and presumed loss of enzyme function, were associated with specific aspects of the PWS phenotype. Aberrant serotonergic functioning is strongly implicated in hyperphagia in PWS, and females with TPH2 T alleles may be at higher risk for affective or mood disorders. Findings hold promise for examining other serotonin-altering genes in PWS, and for future serotonin-altering treatment trials.En ligne : http://dx.doi.org/10.1111/j.1469-7610.2011.02365.x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=121