Relationship among Glutamine, γ-Aminobutyric Acid, and Social Cognition in Autism Spectrum Disorders

Cochran, David; Sikoglu, Elif; Hodge, Steven M.; Edden, Richard A.E.; Foley, Ann; Kennedy, David N.; Moore, Constance M.; Frazier, Jean A.

doi:10.1089/cap.2014.0112

Cited by 98 publications

(89 citation statements)

References 67 publications

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“…Several preclinical and clinical studies have implicated neuroactive amino acids in the etiology of ASD, fragile X syndrome, and tuberous sclerosis complex (TSC), but most of these studies have focused on glutamate, GABA, and/or glutamine (El-Ansary and Al-Ayadhi 2014; Rojas 2014; Santini et al 2014; Rozas et al 2015; Cochran et al 2015; Lozano et al 2015; Robertson et al 2016). Other amino acids could also be involved and it may be important to conduct comprehensive studies in which a number of these amino acids are investigated simultaneously.…”

Section: Neuroactive Amino Acidsmentioning

confidence: 99%

“…Some studies have used magnetic resonance spectroscopy (MRS) to measure amino acid levels in patients with ASD and have reported that patients with ASD have increased GLU levels in brain (Page et al 2006; Joshi et al 2012; Hassan et al 2013). Cochran et al (2015) showed that, compared with HCs, patients with ASD had increased glutamine (GLN) levels, decreased GABA levels, and no difference in GLU levels in brain. However, van Elst et al (2014) reported that GLU and GLN levels were decreased in ASD brains.…”

Section: Glutamate (Glu)mentioning

confidence: 99%

“…Compared with HCs, GABA levels in platelets have been reported to be decreased in ASD (Rolf et al 1993) while those in urine samples increased (Cohen 2002). Neuroimaging techniques reported decreased GABA in brains of ASD patients (Kubas et al 2012; Gaetz et al 2014; Rojas et al 2014; Omura et al 2015; Cochran et al 2015). Rojas et al (2014) reported that the left perisylvian GABA levels were decreased in patients with ASD and their unaffected siblings.…”

Section: Gamma-aminobutyric Acid (Gaba)mentioning

confidence: 99%

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Body fluid levels of neuroactive amino acids in autism spectrum disorders: a review of the literature

Zheng

Wang²,

et al. 2016

Amino Acids

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A review of studies on the body fluid levels of neuroactive amino acids, including glutamate, glutamine, taurine, gamma-aminobutyric acid (GABA), glycine, tryptophan, d-serine, and others, in autism spectrum disorders (ASD) is given. The results reported in the literature are generally inconclusive and contradictory, but there has been considerable variation among the previous studies in terms of factors such as age, gender, number of subjects, intelligence quotient, and psychoactive medication being taken. Future studies should include simultaneous analyses of a large number of amino acids [including d-serine and branched-chain amino acids (BCAAs)] and standardization of the factors mentioned above. It may also be appropriate to use saliva sampling to detect amino acids in ASD patients in the future—this is noninvasive testing that can be done easily more frequently than other sampling, thus providing more dynamic monitoring.

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Section: Neuroactive Amino Acidsmentioning

confidence: 99%

Section: Glutamate (Glu)mentioning

confidence: 99%

Section: Gamma-aminobutyric Acid (Gaba)mentioning

confidence: 99%

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Body fluid levels of neuroactive amino acids in autism spectrum disorders: a review of the literature

Zheng

Wang²,

et al. 2016

Amino Acids

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“…The proton spectra were fit using LCModel (Version 6.3.0) to quantify the creatine levels [27,28] and GANNET software to quantify the GABA-to-creatine ratio (GABA/Cr) [29-34]. …”

Section: Methodsmentioning

confidence: 99%

Perisylvian GABA levels in schizophrenia and bipolar disorder

Atagün

Sikoglu

Soykan

et al. 2017

Neuroscience Letters

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The aim of this study is to measure GABA levels of perisylvian cortices in schizophrenia and bipolar disorder patients, using proton magnetic resonance spectroscopy (1H-MRS). Patients with schizophrenia (n=25), bipolar I disorder (BD-I; n=28) and bipolar II disorder (BD-II; n=20) were compared with healthy controls (n=30). 1H-MRS data was acquired using a Siemens 3 Tesla whole body scanner to quantify right and left perisylvian structures’ (including superior temporal lobes) GABA levels. Right perisylvian GABA values differed significantly between groups [χ2=9.62, df: 3, p = 0.022]. GABA levels were significantly higher in the schizophrenia group compared with the healthy control group (p=0.002). Furthermore, Chlorpromazine equivalent doses of antipsychotics correlated with right hemisphere GABA levels (r2=0.68, p=0.006, n=33). GABA levels are elevated in the right hemisphere in patients with schizophrenia in comparison to bipolar disorder and healthy controls. The balance between excitatory and inhibitory controls over the cortical circuits may have direct relationship with GABAergic functions in auditory cortices. In addition, GABA levels may be altered by brain regions of interest, psychotropic medications, and clinical stage in schizophrenia and bipolar disorder.

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“…Serotonin, a precursor of melatonin, is converted to N-acetylserotonin in the pineal gland by the rate-limiting enzyme arylalkylamine N-acetyltransferase (AA-NAT), followed by the conversion of N-acetylserotonin to melatonin by acetylserotonin methyltransferase. There is a relationship among glutamine, GABA and social cognition in autism [10]. …”

Section: Rationale Of Choice Of Biomarkers (↑ or ↓ Denotes An Increasmentioning

confidence: 99%

Measurement in Saliva From Neurotypical Adults of Biomarkers Pertinent to Autism Spectrum Disorders

Ratajczak¹,

Sothern

2015

Future Sci. OA

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Aim:Measure biomarkers pertinent to autism in saliva from humans.Materials & methods:At 7:30 PM (reading instructions) and 8:30 PM (hearing instructions), neurotypical adults (6 M, 6 F) each spat into tubes containing protease inhibitors. Cells were counted, samples aliquoted, frozen and thawed. Rationale was given for choice of biomarkers. ELISA: CD26, IL-12, carnitine, C4B, GSH, GSSG, MT-2, testosterone, IFN-γ. Mass spectrometry: cystine, glutamine, glutamic acid, GABA, serotonin. Electrochemiluminescentimmunoassay: cortisol. Radioimmunoassay: melatonin.Results:Cells averaged 2.16 × 106/ml. M > F: CD-26, C4B, MT-2. Testosterone, cortisol. Glutamine, glutamic acid, IFN-γ, melatonin and GSSG were measurable. Remaining biomarkers were measured in <50% of samples. Concentrations were equal at both times.Conclusion:Saliva can be collected by literate individuals without added instruction. Ten biomarkers were measurable.

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Relationship among Glutamine, γ-Aminobutyric Acid, and Social Cognition in Autism Spectrum Disorders

Abstract: These data suggest an imbalance between glutamatergic neurotransmission and GABA-ergic neurotransmission in ASD. Higher Gln levels and lower GABA/Cre levels were associated with lower IQ and greater impairments in social cognition across groups.

Cited by 98 publications

References 67 publications

Body fluid levels of neuroactive amino acids in autism spectrum disorders: a review of the literature

Body fluid levels of neuroactive amino acids in autism spectrum disorders: a review of the literature

Perisylvian GABA levels in schizophrenia and bipolar disorder

Measurement in Saliva From Neurotypical Adults of Biomarkers Pertinent to Autism Spectrum Disorders

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