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

Cerebellar gray matter differentiates children with early language delay in autism / Anila M. D'MELLO in Autism Research, 9-11 (November 2016)  

Public ISBD [article]  inAutism Research > 9-11 (November 2016) . - p.1191-1204 Titre : Cerebellar gray matter differentiates children with early language delay in autism Type de document : Texte imprimé et/ou numérique Auteurs : Anila M. D'MELLO, Auteur ; Dorothea M. MOORE, Auteur ; Deana CROCETTI, Auteur ; Stewart H. MOSTOFSKY, Auteur ; Catherine J. STOODLEY, Auteur Article en page(s) : p.1191-1204 Langues : Anglais (eng) Mots-clés : autism  cerebellum  early language delay  voxel-based morphometry  ADOS  imaging Index. décimale : PER Périodiques Résumé : Early language delay (ELD) is one of the earliest indicators of autism spectrum disorder (ASD), and predicts later cognitive and behavioral outcomes. We aimed to determine the neural correlates of ELD in autism, and examine the relationships between gray matter (GM), age of first word/phrase, and core ASD symptoms. We used voxel-based morphometry to examine whole-brain differences in GM in 8–13 year old children with autism (n?=?13 ELD; n?=?22 non-ELD) and 35 age-matched typically developing (TD) children. Multiple regression analyses examined the relationships between GM, age of first word/phrase, and autism diagnostic observation schedule (ADOS) scores. Composite age of first word/phrase negatively correlated with GM throughout the cerebellum. Both ASD groups (ELD and non-ELD) had reduced GM in right cerebellar Crus I/II when compared to TD children. Left cerebellar Crus I/II was the only region in the brain that differentiated ELD and non-ELD children, with ELD children showing reduced GM relative to both non-ELD and TD groups. Group×score interactions converged in left Crus I/II, such that the non-ELD group showed poorer ADOS scores with increasing GM, whereas the ELD group showed poorer ADOS scores as GM decreased. Reduced GM in right cerebellar Crus I/I was related ASD diagnosis, while children with ELD showed additional reduced GM in left Crus I/II. These findings highlight the importance of specific cerebellar networks in both ASD and early language development, and suggest that bilateral disruption in cerebellar regions that interconnect with fronto-parietal networks could impact language acquisition in ASD. En ligne : http://dx.doi.org/10.1002/aur.1622 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=297 [article] Cerebellar gray matter differentiates children with early language delay in autism [Texte imprimé et/ou numérique] / Anila M. D'MELLO, Auteur ; Dorothea M. MOORE, Auteur ; Deana CROCETTI, Auteur ; Stewart H. MOSTOFSKY, Auteur ; Catherine J. STOODLEY, Auteur . - p.1191-1204. Langues : Anglais (eng) in Autism Research > 9-11 (November 2016) . - p.1191-1204 Mots-clés : autism  cerebellum  early language delay  voxel-based morphometry  ADOS  imaging Index. décimale : PER Périodiques Résumé : Early language delay (ELD) is one of the earliest indicators of autism spectrum disorder (ASD), and predicts later cognitive and behavioral outcomes. We aimed to determine the neural correlates of ELD in autism, and examine the relationships between gray matter (GM), age of first word/phrase, and core ASD symptoms. We used voxel-based morphometry to examine whole-brain differences in GM in 8–13 year old children with autism (n?=?13 ELD; n?=?22 non-ELD) and 35 age-matched typically developing (TD) children. Multiple regression analyses examined the relationships between GM, age of first word/phrase, and autism diagnostic observation schedule (ADOS) scores. Composite age of first word/phrase negatively correlated with GM throughout the cerebellum. Both ASD groups (ELD and non-ELD) had reduced GM in right cerebellar Crus I/II when compared to TD children. Left cerebellar Crus I/II was the only region in the brain that differentiated ELD and non-ELD children, with ELD children showing reduced GM relative to both non-ELD and TD groups. Group×score interactions converged in left Crus I/II, such that the non-ELD group showed poorer ADOS scores with increasing GM, whereas the ELD group showed poorer ADOS scores as GM decreased. Reduced GM in right cerebellar Crus I/I was related ASD diagnosis, while children with ELD showed additional reduced GM in left Crus I/II. These findings highlight the importance of specific cerebellar networks in both ASD and early language development, and suggest that bilateral disruption in cerebellar regions that interconnect with fronto-parietal networks could impact language acquisition in ASD. En ligne : http://dx.doi.org/10.1002/aur.1622 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=297

Left-Hemispheric Microstructural Abnormalities in Children With High-Functioning Autism Spectrum Disorder / Daniel PETERSON in Autism Research, 8-1 (February 2015)  

Public ISBD [article]  inAutism Research > 8-1 (February 2015) . - p.61-72 Titre : Left-Hemispheric Microstructural Abnormalities in Children With High-Functioning Autism Spectrum Disorder Type de document : Texte imprimé et/ou numérique Auteurs : Daniel PETERSON, Auteur ; Rajneesh MAHAJAN, Auteur ; Deana CROCETTI, Auteur ; Amanda MEJIA, Auteur ; Stewart MOSTOFSKY, Auteur Article en page(s) : p.61-72 Langues : Anglais (eng) Mots-clés : diffusion tensor imaging (DTI)  neuroimaging  laterality  white matter Index. décimale : PER Périodiques Résumé : Current theories of the neurobiological basis of autism spectrum disorder (ASD) posit an altered pattern of connectivity in large-scale brain networks. Here we used diffusion tensor imaging to investigate the microstructural properties of the white matter (WM) that mediates interregional connectivity in 36 high-functioning children with ASD (HF-ASD) as compared with 37 controls. By employing an atlas-based analysis using large deformation diffeometric morphic mapping registration, a widespread but left-lateralized pattern of abnormalities was revealed. The mean diffusivity (MD) of water in the WM of HF-ASD children was significantly elevated throughout the left hemisphere, particularly in the outer-zone cortical WM. Across diagnostic groups, there was a significant effect of age on left-hemisphere MD, with a similar reduction in MD during childhood in both typically developing and HF-ASD children. The increased MD in children with HF-ASD suggests hypomyelination and may reflect increased short-range cortico-cortical connections subsequent to early WM overgrowth. These findings also highlight left-hemispheric connectivity as relevant to the pathophysiology of ASD and indicate that the spatial distribution of microstructural abnormalities in HF-ASD is widespread and left-lateralized. This altered left-hemispheric connectivity may contribute to deficits in communication and praxis observed in ASD. Autism Res 2015, 8: 61–72. En ligne : http://dx.doi.org/10.1002/aur.1413 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=256 [article] Left-Hemispheric Microstructural Abnormalities in Children With High-Functioning Autism Spectrum Disorder [Texte imprimé et/ou numérique] / Daniel PETERSON, Auteur ; Rajneesh MAHAJAN, Auteur ; Deana CROCETTI, Auteur ; Amanda MEJIA, Auteur ; Stewart MOSTOFSKY, Auteur . - p.61-72. Langues : Anglais (eng) in Autism Research > 8-1 (February 2015) . - p.61-72 Mots-clés : diffusion tensor imaging (DTI)  neuroimaging  laterality  white matter Index. décimale : PER Périodiques Résumé : Current theories of the neurobiological basis of autism spectrum disorder (ASD) posit an altered pattern of connectivity in large-scale brain networks. Here we used diffusion tensor imaging to investigate the microstructural properties of the white matter (WM) that mediates interregional connectivity in 36 high-functioning children with ASD (HF-ASD) as compared with 37 controls. By employing an atlas-based analysis using large deformation diffeometric morphic mapping registration, a widespread but left-lateralized pattern of abnormalities was revealed. The mean diffusivity (MD) of water in the WM of HF-ASD children was significantly elevated throughout the left hemisphere, particularly in the outer-zone cortical WM. Across diagnostic groups, there was a significant effect of age on left-hemisphere MD, with a similar reduction in MD during childhood in both typically developing and HF-ASD children. The increased MD in children with HF-ASD suggests hypomyelination and may reflect increased short-range cortico-cortical connections subsequent to early WM overgrowth. These findings also highlight left-hemispheric connectivity as relevant to the pathophysiology of ASD and indicate that the spatial distribution of microstructural abnormalities in HF-ASD is widespread and left-lateralized. This altered left-hemispheric connectivity may contribute to deficits in communication and praxis observed in ASD. Autism Res 2015, 8: 61–72. En ligne : http://dx.doi.org/10.1002/aur.1413 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=256

Motor Circuit Anatomy in Children with Autism Spectrum Disorder With or Without Attention Deficit Hyperactivity Disorder / Rajneesh MAHAJAN in Autism Research, 9-1 (January 2016)  

Public ISBD [article]  inAutism Research > 9-1 (January 2016) . - p.67-81 Titre : Motor Circuit Anatomy in Children with Autism Spectrum Disorder With or Without Attention Deficit Hyperactivity Disorder Type de document : Texte imprimé et/ou numérique Auteurs : Rajneesh MAHAJAN, Auteur ; Benjamin DIRLIKOV, Auteur ; Deana CROCETTI, Auteur ; Stewart H. MOSTOFSKY, Auteur Article en page(s) : p.67-81 Langues : Anglais (eng) Mots-clés : structural MRI  motor circuit  autism spectrum disorder  attention deficit hyperactivity disorder Index. décimale : PER Périodiques Résumé : This study examined the morphology of frontal-parietal regions relevant to motor functions in children with autism spectrum disorder (ASD) with or without attention deficit hyperactivity disorder (ADHD). We also explored its associations with autism severity and motor skills, and the impact of comorbid ADHD on these associations. Participants included 126 school-age children: 30 had ASD only, 33 had ASD with ADHD, and 63 were typically developing. High resolution 3T MPRAGE images were acquired to examine the cortical morphology (gray matter volume, GMV, surface area, SA, and cortical thickness, CT) in three regions of interest (ROI): precentral gyrus (M1), postcentral gyrus (S1), and inferior parietal cortex (IPC). Children with ASD showed abnormal increases in GMV and SA in all three ROIs: (a) increased GMV in S1 bilaterally and in right M1 was specific to children with ASD without ADHD; (b) all children with ASD (with or without ADHD) showed increases in the left IPC SA. Furthermore, on measures of motor function, impaired praxis was associated with increased GMV in right S1 in the ASD group with ADHD. Children with ASD with ADHD showed a positive relationship between bilateral S1 GMV and manual dexterity, whereas children with ASD without ADHD showed a negative relationship. Our findings suggest that (a) ASD is associated with abnormal morphology of cortical circuits crucial to motor control and learning; (b) anomalous overgrowth of these regions, particularly S1, may contribute to impaired motor skill development, and (c) functional and morphological differences are apparent between children with ASD with or without ADHD. En ligne : http://dx.doi.org/10.1002/aur.1497 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=282 [article] Motor Circuit Anatomy in Children with Autism Spectrum Disorder With or Without Attention Deficit Hyperactivity Disorder [Texte imprimé et/ou numérique] / Rajneesh MAHAJAN, Auteur ; Benjamin DIRLIKOV, Auteur ; Deana CROCETTI, Auteur ; Stewart H. MOSTOFSKY, Auteur . - p.67-81. Langues : Anglais (eng) in Autism Research > 9-1 (January 2016) . - p.67-81 Mots-clés : structural MRI  motor circuit  autism spectrum disorder  attention deficit hyperactivity disorder Index. décimale : PER Périodiques Résumé : This study examined the morphology of frontal-parietal regions relevant to motor functions in children with autism spectrum disorder (ASD) with or without attention deficit hyperactivity disorder (ADHD). We also explored its associations with autism severity and motor skills, and the impact of comorbid ADHD on these associations. Participants included 126 school-age children: 30 had ASD only, 33 had ASD with ADHD, and 63 were typically developing. High resolution 3T MPRAGE images were acquired to examine the cortical morphology (gray matter volume, GMV, surface area, SA, and cortical thickness, CT) in three regions of interest (ROI): precentral gyrus (M1), postcentral gyrus (S1), and inferior parietal cortex (IPC). Children with ASD showed abnormal increases in GMV and SA in all three ROIs: (a) increased GMV in S1 bilaterally and in right M1 was specific to children with ASD without ADHD; (b) all children with ASD (with or without ADHD) showed increases in the left IPC SA. Furthermore, on measures of motor function, impaired praxis was associated with increased GMV in right S1 in the ASD group with ADHD. Children with ASD with ADHD showed a positive relationship between bilateral S1 GMV and manual dexterity, whereas children with ASD without ADHD showed a negative relationship. Our findings suggest that (a) ASD is associated with abnormal morphology of cortical circuits crucial to motor control and learning; (b) anomalous overgrowth of these regions, particularly S1, may contribute to impaired motor skill development, and (c) functional and morphological differences are apparent between children with ASD with or without ADHD. En ligne : http://dx.doi.org/10.1002/aur.1497 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=282

Reduced GABA and altered somatosensory function in children with autism spectrum disorder / Nicolaas A. J. PUTS in Autism Research, 10-4 (April 2017)  

Public ISBD [article]  inAutism Research > 10-4 (April 2017) . - p.608-619 Titre : Reduced GABA and altered somatosensory function in children with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Nicolaas A. J. PUTS, Auteur ; Ericka L. WODKA, Auteur ; Ashley D. HARRIS, Auteur ; Deana CROCETTI, Auteur ; Mark TOMMERDAHL, Auteur ; Stewart H. MOSTOFSKY, Auteur ; Richard A. E. EDDEN, Auteur Article en page(s) : p.608-619 Langues : Anglais (eng) Mots-clés : autism  somatosensory  GABA  magnetic resonance spectroscopy  tactile  MRS  touch Index. décimale : PER Périodiques Résumé : Background: Abnormal responses to tactile stimuli are a common feature of autism spectrum disorder (ASD). Several lines of evidence suggest that GABAergic function, which has a crucial role in tactile processing, is altered in ASD. In this study, we determine whether in vivo GABA levels are altered in children with ASD, and whether alterations in GABA levels are associated with abnormal tactile function in these children. Methods: GABA-edited magnetic resonance spectroscopy was acquired in 37 children with Autism and 35 typically developing children (TDC) from voxels over primary sensorimotor and occipital cortices. Children performed tactile tasks previously shown to be altered in ASD, linked to inhibitory mechanisms. Detection threshold was measured with- and without the presence of a slowly increasing sub-threshold stimulus. Amplitude discrimination was measured with- and without the presence of an adapting stimulus, and frequency discrimination was measured. Results: Sensorimotor GABA levels were significantly reduced in children with autism compared to healthy controls. Occipital GABA levels were normal. Sensorimotor GABA levels correlated with dynamic detection threshold as well as with the effect of sub-threshold stimulation. Sensorimotor GABA levels also correlated with amplitude discrimination after adaptation (an effect absent in autism) and frequency discrimination in controls, but not in children with autism. Conclusions: GABA levels correlate with behavioral measures of inhibition. Children with autism have reduced GABA, associated with abnormalities in tactile performance. We show here that altered in vivo GABA levels might predict abnormal tactile information processing in ASD and that the GABA system may be a future target for therapies. En ligne : http://dx.doi.org/10.1002/aur.1691 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=307 [article] Reduced GABA and altered somatosensory function in children with autism spectrum disorder [Texte imprimé et/ou numérique] / Nicolaas A. J. PUTS, Auteur ; Ericka L. WODKA, Auteur ; Ashley D. HARRIS, Auteur ; Deana CROCETTI, Auteur ; Mark TOMMERDAHL, Auteur ; Stewart H. MOSTOFSKY, Auteur ; Richard A. E. EDDEN, Auteur . - p.608-619. Langues : Anglais (eng) in Autism Research > 10-4 (April 2017) . - p.608-619 Mots-clés : autism  somatosensory  GABA  magnetic resonance spectroscopy  tactile  MRS  touch Index. décimale : PER Périodiques Résumé : Background: Abnormal responses to tactile stimuli are a common feature of autism spectrum disorder (ASD). Several lines of evidence suggest that GABAergic function, which has a crucial role in tactile processing, is altered in ASD. In this study, we determine whether in vivo GABA levels are altered in children with ASD, and whether alterations in GABA levels are associated with abnormal tactile function in these children. Methods: GABA-edited magnetic resonance spectroscopy was acquired in 37 children with Autism and 35 typically developing children (TDC) from voxels over primary sensorimotor and occipital cortices. Children performed tactile tasks previously shown to be altered in ASD, linked to inhibitory mechanisms. Detection threshold was measured with- and without the presence of a slowly increasing sub-threshold stimulus. Amplitude discrimination was measured with- and without the presence of an adapting stimulus, and frequency discrimination was measured. Results: Sensorimotor GABA levels were significantly reduced in children with autism compared to healthy controls. Occipital GABA levels were normal. Sensorimotor GABA levels correlated with dynamic detection threshold as well as with the effect of sub-threshold stimulation. Sensorimotor GABA levels also correlated with amplitude discrimination after adaptation (an effect absent in autism) and frequency discrimination in controls, but not in children with autism. Conclusions: GABA levels correlate with behavioral measures of inhibition. Children with autism have reduced GABA, associated with abnormalities in tactile performance. We show here that altered in vivo GABA levels might predict abnormal tactile information processing in ASD and that the GABA system may be a future target for therapies. En ligne : http://dx.doi.org/10.1002/aur.1691 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=307

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