Neurometabolite levels in the brains of patients with autism spectrum disorders: A meta-analysis of proton magnetic resonance spectroscopy studies (N = 1501)

Du, Yang; Chen, Lei; Yan, Meichen; Wang, Yanli; Zhong, Xiaolin; Xv, Chen-Xi; Li, Yao-Bo; Cheng, Yong

doi:10.1038/s41380-023-02079-y

Cited by 16 publications

(11 citation statements)

References 103 publications

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“…Our findings of no significant GABA+ differences between autistic children and TDC are consistent with several recent in vivo studies comparing GABA+ levels between autistic and TDC groups in the thalamus (He et al, 2021), ACC (Ajram et al, 2017;Cochran et al, 2015;Goji et al, 2017), frontal cortex (Ajram et al, 2017;Brix et al, 2015;Du et al, 2023), SM1 (He et al, 2021;Robertson et al, 2016), left lenticular nucleus (Harada et al, 2011), occipital cortex (Drenthen et al, 2016;Gaetz et al, 2014;Puts et al, 2017;Robertson et al, 2016), and cerebellum (Goji et al, 2017), at 3T using the MEGA-PRESS sequence. However, findings from the literature related to GABA+ levels in autism are mixed; some studies (including our own) have reported lower GABA+ levels in ACC (Ito et al, 2017), frontal cortex (Harada et al, 2011), SM1 (Gaetz et al, 2014;Puts et al, 2017), temporal cortex (Gaetz et al, 2014;Port et al, 2017;Rojas et al, 2014), and cerebellum (Ito et al, 2017) in autistic children using MEGA-PRESS at 3T.…”

Section: Discussionsupporting

confidence: 92%

Brain glutathione and GABA+ levels in autistic children

Song,

Hupfeld,

Davies‐Jenkins

et al. 2024

Autism Research

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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.

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Section: Discussionsupporting

confidence: 92%

Brain glutathione and GABA+ levels in autistic children

Song,

Hupfeld,

Davies‐Jenkins

et al. 2024

Autism Research

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“…This was not considered by previous systematic reviews (Ajram et al, 2019; Y. Du et al, 2023; Ford & Crewther, 2016a). We have also comprehensively assessed the impact of study design on outcome to expose confounding factors in our results.…”

Section: Discussionmentioning

confidence: 99%

Neurometabolite differences in Autism as assessed with Magnetic Resonance Spectroscopy: a systematic review and meta-analysis

Thomson,

Pasanta,

Arichi

et al. 2024

Preprint

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Abstract1H-Magnetic Resonance Spectroscopy (MRS)is a non-invasive technique that can be used to quantify the concentrations of metabolites in the brain in vivo. MRS findings in the context of autism are inconsistent and conflicting. We performed asystematic review and meta-analysisof MRS studies observing glutamate and gamma-aminobutyric acid (GABA), as well as brain metabolites involved in energy metabolism (glutamine, creatine), neural integrity (e.g. n-acetyl aspartate (NAA), choline, myo-inositol) and neuro-inflammation (glutathione) in autism cohorts. Data were extracted and grouped by metabolite, brain region and several other factors before calculation of standardised effect sizes. Overall, we find significantly lower concentrations of GABA and NAA in autism, indicative of disruptions to the balance between excitation/inhibition within brain circuits, as well as neural integrity. Further analysis found these alterations are most pronounced in autistic children and in limbic brain regions relevant to autism phenotypes. Additionally, we show how study outcome varies due to demographic and methodological factors (e.g. medication use), emphasising the importance of conforming with consensus study designs and transparent reporting.HighlightsWe performed a meta-analysis ofMagnetic Resonance Spectroscopyfindings in autism.We find significantly lower concentrations of GABA and NAA in children with autism.These alterations were most pronounced in limbic brain regions.Demographic factors (including sex) contribute to MRS study outcome variation.

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“…The primary metabolites assessed include N-acetylaspartate-containing compounds (NAA), creatine-containing compounds (Cr), choline-containing compounds (Cho), glutamate + glutamine (Glx), myo-inositol (mI), and gamma-aminobutyric acid (GABA). NAA, predominantly located within neurons and axons, serves as a biomarker for neuronal density, heterogeneity, and vitality [127,128]. Compared with TD children, children with ASD show a decrease in NAA concentrations.…”

Section: Proton Magnetic Resonance Spectroscopy-based Biochemical Met...mentioning

confidence: 99%

“…Compared with TD children, children with ASD show a decrease in NAA concentrations. This decline primarily occurs in the left amygdala [129], bilateral orbitofrontal cortex [118], thalamus [130], anterior cingulate cortex [119,131], temporal cortex, cerebellum [127], and parietal lobe [132]. These reductions reflect impaired, diminished, or immature neuronal function in ASD, which is associated with social deficits and memory impairments [129,132].…”

Section: Proton Magnetic Resonance Spectroscopy-based Biochemical Met...mentioning

confidence: 99%

Application of Multimodal MRI in the Early Diagnosis of Autism Spectrum Disorders: A Review

Wang,

Xu,

Zhang

et al. 2023

Diagnostics

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Autism spectrum disorder (ASD) is a neurodevelopmental disorder in children. Early diagnosis and intervention can remodel the neural structure of the brain and improve quality of life but may be inaccurate if based solely on clinical symptoms and assessment scales. Therefore, we aimed to analyze multimodal magnetic resonance imaging (MRI) data from the existing literature and review the abnormal changes in brain structural–functional networks, perfusion, neuronal metabolism, and the glymphatic system in children with ASD, which could help in early diagnosis and precise intervention. Structural MRI revealed morphological differences, abnormal developmental trajectories, and network connectivity changes in the brain at different ages. Functional MRI revealed disruption of functional networks, abnormal perfusion, and neurovascular decoupling associated with core ASD symptoms. Proton magnetic resonance spectroscopy revealed abnormal changes in the neuronal metabolites during different periods. Decreased diffusion tensor imaging signals along the perivascular space index reflected impaired glymphatic system function in children with ASD. Differences in age, subtype, degree of brain damage, and remodeling in children with ASD led to heterogeneity in research results. Multimodal MRI is expected to further assist in early and accurate clinical diagnosis of ASD through deep learning combined with genomics and artificial intelligence.

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Neurometabolite levels in the brains of patients with autism spectrum disorders: A meta-analysis of proton magnetic resonance spectroscopy studies (N = 1501)

Cited by 16 publications

References 103 publications

Brain glutathione and GABA+ levels in autistic children

Brain glutathione and GABA+ levels in autistic children

Neurometabolite differences in Autism as assessed with Magnetic Resonance Spectroscopy: a systematic review and meta-analysis

Application of Multimodal MRI in the Early Diagnosis of Autism Spectrum Disorders: A Review

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