Distinct Plasma Profile of Polar Neutral Amino Acids, Leucine, and Glutamate in Children with Autism Spectrum Disorders

Tirouvanziam, Rabindra; Obukhanych, Tetyana V.; Laval, Julie; Aronov, Pavel A.; Libove, Robin A.; Banerjee, Arpita Goswami; Parker, Karen J.; O’Hara, Ruth; Herzenberg, Leonard A.; Herzenberg, Leonore A.; Hardan, Antonio Y.

doi:10.1007/s10803-011-1314-x

Cited by 68 publications

(73 citation statements)

References 31 publications

(27 reference statements)

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“…Social subscale scores on the ADI-R were correlated with glutamate (I.e., higher serum glutamate associated with poorer social ability). Three more recent studies using case controls have also reported significantly increased plasma glutamate (Tirouvanziam et al 2011; Shimmura et al 2011; Hassan et al 2013). Only a single early study of plasma glutamate levels has failed to report increases in autism - Rolf et al (1993) reported reduced glutamate in platelet rich samples from 18 individuals with autism.…”

Section: Elevated Blood Plasma and Serum In Autismmentioning

confidence: 88%

The role of glutamate and its receptors in autism and the use of glutamate receptor antagonists in treatment

Rojas

2014

J Neural Transm

168

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Glutamate is the major excitatory neurotransmitter in the brain and may be a key neurotransmitter involved in autism. Literature pertaining to glutamate and autism or related disorders (e.g., Fragile X syndrome) is reviewed in this article. Interest in glutamatergic dysfunction in autism is high due to increasing convergent evidence implicating the system in the disorder from peripheral biomarkers, neuroimaging, protein expression, genetics and animal models. Currently, there are no pharmaceutical interventions approved for autism that address glutamate deficits in the disorder. New treatments related to glutamatergic neurotransmission, however, are emerging. In addition, older glutamate-modulating medications with approved indications for use in other disorders are being investigated for re-tasking as treatments for autism. This review presents evidence in support of glutamate abnormalities in autism and the potential for translation into new treatments for the disorder.

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Section: Elevated Blood Plasma and Serum In Autismmentioning

confidence: 88%

The role of glutamate and its receptors in autism and the use of glutamate receptor antagonists in treatment

Rojas

2014

J Neural Transm

168

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“…Studies on GLU levels in the plasma of patients with ASD compared to healthy controls (HCs) are contradictory, with some reporting increased levels (Moreno-Fuenmayor et al 1996; Aldred et al 2003; MacDermot et al 2005; Shimmura et al 2011; Tirouvanziam et al 2011; Naushad et al 2013; El-Ansary and Al-Ayadhi 2014; Cai et al 2016) and some decreased levels (El-Ansary 2016). In addition, increased levels have been reported in serum (Shinohe et al 2006) and decreased levels in platelets (Rolf et al 1993) and urine samples (Evans et al 2008; Yap et al 2010; Nadal-Desbarats et al 2014).…”

Section: Glutamate (Glu)mentioning

confidence: 99%

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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“…Glutamic acid decarboxylase, an enzyme that catalyzes the decarboxylation of glutamate to GABA, has also been reported to be reduced in parietal and cerebellar cortices of individuals with autism (9). Finally, increases in glutamate levels in serum (10, 11) and cerebrospinal fluid (12, 13) have also been observed in children with autism.…”

Section: Introductionmentioning

confidence: 97%

A Randomized Controlled Pilot Trial of Oral N-Acetylcysteine in Children with Autism

Hardan¹,

Fung²,

Libove³

et al. 2012

Biological Psychiatry

Self Cite

250

189

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Background An imbalance in the excitatory/inhibitory systems with abnormalities in the glutamatergic pathways has been implicated in the pathophysiology of autism. Furthermore, chronic redox imbalance was also recently linked to this disorder. The goal of this pilot study was to assess the feasibility of using oral N-acetylcysteine (NAC), a glutamatergic modulator and an antioxidant in the treatment of behavioral disturbance in children with autism. Methods This is a 12-week, double-blind, randomized, placebo-controlled study of NAC in children with autistic disorder. Subjects randomized to NAC were initiated at 900 mg daily for 4 weeks, then 900 mg twice-daily for 4 weeks and 900 mg three-times-daily for 4 weeks. The primary behavioral measure (Aberrant Behavior Checklist – Irritability subscale) and safety measures were performed at baseline, 4, 8, and 12 weeks. Secondary measures included the ABC-Stereotypy subscale, Repetitive Behavior Scale – Revised (RBS-R), and Social Responsiveness Scale (SRS). Results Thirty-three subjects (31 males, 2 females; aged 3.2–10.7 years) were randomized in the study. Follow-up data was available on fourteen subjects in the NAC group and fifteen in the placebo group. Oral NAC was well-tolerated with limited side effects. Compared to placebo, NAC resulted in significant improvements on ABC-Irritability subscale (F=6.80; p<.001; d=.96). Conclusions Data from this pilot investigation support the potential usefulness of NAC for treating irritability in children with autistic disorder. Large randomized controlled investigations are warranted. ClinicalTrials.gov Identifier NCT00627705

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Distinct Plasma Profile of Polar Neutral Amino Acids, Leucine, and Glutamate in Children with Autism Spectrum Disorders

Cited by 68 publications

References 31 publications

The role of glutamate and its receptors in autism and the use of glutamate receptor antagonists in treatment

The role of glutamate and its receptors in autism and the use of glutamate receptor antagonists in treatment

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

A Randomized Controlled Pilot Trial of Oral N-Acetylcysteine in Children with Autism

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