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Abstract
ObjectiveGlutamate plays an important role in brain development, neuronal migration, differentiation, survival and synaptogenesis. Recent studies have explored the relationship between blood glutamate levels and autism spectrum disorder (ASD). However, the findings are inconsistent. We undertook the first systematic review with a meta-analysis of studies examining blood glutamate levels in ASD compared with controls.MethodsA literature search was conducted using PubMed, Embase, and the Cochrane Library for studies published before March 2016. A random-effects model was used to calculate the pooled standardized mean difference (SMD) of the outcomes. Subgroup analyses were used to explore the potential sources of heterogeneity, and the publication bias was estimated using Egger’s tests.ResultsTwelve studies involving 880 participants and 446 incident cases were included in this meta-analysis. The meta-analysis provided evidence for higher blood glutamate levels in ASD [SMD = 0.99, 95% confidence interval (95% CI) = 0.58–1.40; P < 0.001] with high heterogeneity (I2 = 86%, P < 0.001) across studies. The subgroup analyses revealed higher glutamate levels in ASD compared with controls in plasma [SMD = 1.04, 95% CI = 0.58–1.50; P < 0.001] but not true in serum [SMD = 0.79, 95% CI = -0.41–1.99; P = 0.20]. Studies employing high performance liquid chromatography (HPLC) or liquid chromatography-tandem mass spectrometry (LC-MS) assays also revealed higher blood glutamate levels in ASD. A sensitivity analysis found that the results were stable, and there was no evidence of publication bias.ConclusionsBlood glutamate levels might be a potential biomarker of ASD.
Highlights
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by abnormalities in social interactions, impairments in language and communication, restrictive or repetitive interests, and stereotyped behaviors and movements [1]
The meta-analysis provided evidence for higher blood glutamate levels in ASD [standardized mean difference (SMD) = 0.99, 95% confidence interval = 0.58–1.40; P < 0.001] with high heterogeneity (I2 = 86%, P < 0.001) across studies
The subgroup analyses revealed higher glutamate levels in ASD compared with controls in plasma [SMD = 1.04, 95% confidence interval (95% CI) = 0.58– 1.50; P < 0.001] but not true in serum [SMD = 0.79, 95% CI = -0.41–1.99; P = 0.20]
Summary
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by abnormalities in social interactions, impairments in language and communication, restrictive or repetitive interests, and stereotyped behaviors and movements [1]. Receiving diagnosis at an early stage of development could contribute to the acquisition of optimized coping strategies for ASD. Diagnosis of ASD is based solely on complex behavioral abnormalities, which are not evident until approximately 12–18 months of age [5, 6]. Individuals with ASD vary enormously in their clinical manifestations, severity and response to treatment. This complexity is urging an intensive search to identify biomarkers to aid clinicians in achieving an early and more precise diagnosis [7]
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