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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)

Molecular Psychiatry volume 28, pages 3092–3103 (2023)Cite this article

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Abstract

Evidence suggests that neurometabolite alterations may be involved in the pathophysiology of autism spectrum disorders (ASDs). We performed a meta-analysis of proton magnetic resonance spectroscopy (1H-MRS) studies to examine the neurometabolite levels in the brains of patients with ASD. A systematic search of PubMed and Web of Science identified 54 studies for the meta-analysis. A random-effects meta-analysis demonstrated that compared with the healthy controls, patients with ASD had lower N-acetyl-aspartate-containing compound (NAA) and choline-containing compound (Cho) levels and NAA/(creatine-containing compound) Cr ratios in the gray matter and lower NAA and glutamate + glutamine (Glx) levels in the white matter. Furthermore, NAA and gamma-aminobutyric acid (GABA) levels, NAA/Cr ratios, and GABA/Cr ratios were significantly decreased in the frontal cortex of patients with ASD, whereas glutamate (Glu) levels were increased in the prefrontal cortex. Additionally, low NAA levels and GABA/Cr ratios in the temporal cortex, low NAA levels and NAA/Cr ratios in the parietal and dorsolateral prefrontal cortices, and low NAA levels in the cerebellum and occipital cortex were observed in patients with ASD. Meta-regression analysis revealed that age was positively associated with effect size in studies analyzing the levels of gray matter NAA and white matter Glx. Taken together, these results provide strong clinical evidence that neurometabolite alterations in specific brain regions are associated with ASD and age is a confounding factor for certain neurometabolite levels in patients with ASD.

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Fig. 1: PRISMA flowchart of the literature search.
Fig. 2: Forest plot for random-effects meta-analysis for NAA/Cr, Glx and Cho in gray matter and white matter.
Fig. 3: Forest plot for random-effects meta-analysis for NAA in frontal cortex and parietal cortex.
Fig. 4: Forest plot for random-effects meta-analysis for Glu, Glx and GABA in various brain regions.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (82071676) and the High-Level Hospital Development Program for Foshan “Climbing” Project.

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Authors and Affiliations

  1. Key Laboratory of Ethnomedicine of Ministry of Education, Center on Translational Neuroscience, College of Life and Environmental Sciences, Minzu University of China, Beijing, China

    Yang Du, Lei Chen, Mei-Chen Yan, Yan-Li Wang, Xiao-Lin Zhong, Chen-Xi Xv, Yao-Bo Li & Yong Cheng

  2. Institute of National Security, Minzu University of China, Beijing, China

    Yong Cheng

  3. NHC Key Laboratory of Birth Defect Research, Prevention, and Treatment (Hunan Provincial Maternal and Child Health-Care Hospital), Changsha, Hunan, China

    Yong Cheng

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  1. Yang Du
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  2. Lei Chen
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  3. Mei-Chen Yan
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  4. Yan-Li Wang
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  8. Yong Cheng
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Contributions

YC conceived and designed this study; YD and MCY extracted the data; all authors analyzed and interpreted the data; and YD drafted the manuscript with critical revisions from YC, LC, and MCY.

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Correspondence to Yong Cheng.

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Du, Y., Chen, L., Yan, MC. et al. Neurometabolite levels in the brains of patients with autism spectrum disorders: A meta-analysis of proton magnetic resonance spectroscopy studies (N = 1501). Mol Psychiatry 28, 3092–3103 (2023). https://doi.org/10.1038/s41380-023-02079-y

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