Blood and brain glutamate levels in children with autistic disorder

Hassan, Tamer; Abdelrahman, Hadeel M.; Fattah, Nelly R. Abdel; Elmasry, Nagda M; Hashim, Haitham M.; El-Gerby, Khaled M.; Fattah, Nermin R. Abdel

doi:10.1016/j.rasd.2012.12.005

Cited by 69 publications

(69 citation statements)

References 35 publications

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“…It is still unclear whether peripheral glutamate levels reflect similar changes in the central nervous system. However, a previous study reported that there was a highly significant positive correlation between blood glutamate level and brain glutamate levels in the four brain regions tested (P <0.001) [18].…”

Section: Discussionmentioning

confidence: 72%

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Elevated plasma levels of glutamate in children with autism spectrum disorders

et al. 2016

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Excitatory neurotransmitter signaling through glutamate receptors modulates cognitive functions such as memory and learning, which are usually impaired in autism spectrum disorders (ASD). The aim of this study was to assess the clinical significance of plasma glutamate levels in ASD. Fifty-one children diagnosed with ASD, 51 typically developing children, and 51 children with intellectual disability matched for sex and age were assessed for plasma glutamate at admission. Plasma levels of glutamate were measured by liquid chromatography-tandem mass spectrometry and the severity of ASD was evaluated using the Childhood Autism Rating Scale Score. We found that the mean plasma glutamate levels were significantly (P<0.0001) higher in children with ASD compared with healthy controls and intellectual disability controls [36.1 (SD: 8.3) vs. 23.4 (4.2) vs. 24.7 (4.6) µM; P<0.001, respectively]. Levels of glutamate increased with increasing severity of ASD as defined by the Childhood Autism Rating Scale score. Receiver operating characteristics to diagnose ASD showed areas under the curve of glutamate of 0.92 [95% confidence interval (CI), 0.87-0.96], which was superior to high-sensitivity C-reactive protein [0.64 (95% CI, 0.55-0.75), P<0.001] and homocysteine (area under the curve, 0.72; 95% CI, 0.64-0.81; P<0.000). In multivariate logistic regression analysis, glutamate was an independent diagnosis indicator of ASD with an adjusted odds ratio of 1.362 (95% CI, 1.164-1.512; P<0.0001). The present study shows that autistic children had higher plasma levels of glutamate and elevated plasma glutamate levels may play an important role in the pathogenesis of autism. Further larger studies are required to support our findings.

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Section: Discussionmentioning

confidence: 72%

“…Hassan et al [18] found that the mean blood and brain glutamate levels were significantly higher in patients with autistic disorder than controls (P < 0.001). van Elst et al [19] found that there was a link between disturbances of the glutamate metabolism and adult autism.…”

Section: Discussionmentioning

confidence: 98%

Elevated plasma levels of glutamate in children with autism spectrum disorders

et al. 2016

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“…Rojas, 2013); and the cerebellum; striatum and frontal lobe (Hassan et al, 2013). However, other studies have found decreased glutamate/Glx in ASD in regions including the ACC (Bernardi et al, 2011;van Elst, Maier, Fangmeier, & Endres, 2014) the basal ganglia (Horder et al, 2013); frontal and occipital cortex, the cerebellum (Devito et al, 2007) and white matter (Corrigan et al, 2013).…”

Section: Glutamate / Glxmentioning

confidence: 97%

“…Blood plasma glutamate levels have been found to be increased (Hassan et al, 2013) and platelet levels of its precursor glutamine, decreased (Rolf, Haarmann, Grotemeyer, & Kehrer, 1993) in participants with ASD compared to neurotypical controls. Similarly, whilst Dhossche et al (2002) reported higher blood plasma GABA levels in children with ASD, decreased platelet levels of GABA have also been reported (Rolf et al, 1993).…”

Section: Blood Measurementmentioning

confidence: 99%

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Measuring neural excitation and inhibition in autism: Different approaches, different findings and different interpretations

2016

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The balance of neural excitation and inhibition (E/I balance) is often hypothesised to be altered in autism spectrum disorder (ASD). One widely held view is that excitation levels are elevated relative to inhibition in ASD. Understanding whether, and how, E/I balance may be altered in ASD is important given the recent interest in trialling pharmacological interventions for ASD which target inhibitory neurotransmitter function.Here we provide a critical review of evidence for E/I balance in ASD. We conclude that data from a number of domains provides support for alteration in excitation and inhibitory neurotransmission in ASD, but when considered collectively, the available literature provide little evidence to support claims for either a net increase in excitation or a net increase in inhibition. Strengths and limitations of available techniques are considered, and directions for future research discussed.3

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Increased prefrontal GABA concentrations in adults with autism spectrum disorders

Maier

Düppers²,

Runge

et al. 2022

Autism Research

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The excitatory-inhibitory imbalance hypothesis postulates dysregulation of the gamma-aminobutyric acid (GABA) and glutamate (Glu) neurotransmitter systems as a common underlying deficit in individuals with autism spectrum disorders (ASD). Previous studies suggest an important role of these systems in the pathophysiology of ASD, including a study of our group reporting decreased glutamate concentrations in the pregenual anterior cingulate cortex (ACC) of adults with ASD. The aim of this study was to replicate our previous findings of impaired glutamate metabolism in ASD in a new sample and to additionally quantify GABA in the ACC and dorsolateral prefrontal cortex (dlPFC). Concentrations of GABA and glutamate-glutamine (Glx; combined glutamate and glutamine signal) were quantified in the ACC and dlPFC of 43 adults with ASD and 43 neurotypical controls (NTC) by magnetic resonance spectroscopy (MRS). The ASD group showed increased absolute GABA concentrations and elevated GABA/creatine ratios in the left dlPFC compared to NTC, while no group differences were detected in the pregenual and dorsal ACC. Previous findings of altered Glx concentration in the pregenual ACC of the ASD group could not be replicated. Regarding Glx concentrations and Glx/creatine ratios, there were no significant differences in the dlPFC and ACC either. The study supports the hypothesis of an altered GABA and glutamate equilibrium, indicating an imbalance between excitatory and inhibitory metabolism in ASD patients. However, inconsistent results across studies and brain regions suggest a complex underlying phenomenon. Lay Summary:• Adults of the autism spectrum exhibit elevated levels of the inhibitory neurotransmitter GABA in the left dorsolateral prefrontal cortex. • This finding supports the hypothesis of an imbalance between excitatory and inhibitory equilibrium in patients with autism spectrum disorders.

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Blood and brain glutamate levels in children with autistic disorder

Cited by 69 publications

References 35 publications

Elevated plasma levels of glutamate in children with autism spectrum disorders

Elevated plasma levels of glutamate in children with autism spectrum disorders

Measuring neural excitation and inhibition in autism: Different approaches, different findings and different interpretations

Increased prefrontal GABA concentrations in adults with autism spectrum disorders

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