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

Amino Acids, Sep 2016

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

Amino Acids Body fluid levels of neuroactive amino acids in autism spectrum disorders: a review of the literature Hui‑Fei Zheng 0 1 Wen‑Qiang Wang 0 1 Xin‑Min Li 0 1 Gail Rauw 0 1 Glen B. Baker 0 1 Handling Editor: J. D. Wade. 0 1 0 Neurochemical Research Unit, Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta , Edmonton, AB , Canada 1 Mental Health Research Laboratory, Xiamen Xianyue Hospital , Xiamen, Fujian , China 2 Glen B. Baker 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. Amino acids; Autism spectrum disorders; Glutamate; Glutamine; Taurine; GABA; Glycine; Tryptophan; d -Serine - The term autism spectrum disorders (ASD) refers to neurodevelopmental diseases that affect 1–2 % of children, according to the data on the broad array of ASD ( BaronCohen et al. 2009 ). ASD is characterized by different levels of severity and occurs in all ethnic groups. Noto et al. (2014) reported that 1 out of 88 children aged 8 years will develop an ASD, with males more at risk than females. Blumberg et al. (2013) showed that the prevalence of ASD had risen 75 % from 2007 to 2012 in the United States. Feng et al. (2013) identified 12 studies when searching Chinese databases in 2013; the prevalence in these studies varied from 2.8 to 29.5/10,000. ASD is characterized by impaired social interaction skills combined with restrictive/repetitive behaviors (American Psychiatric Association 2013) . Genetic predisposition and environmental factors undoubtedly have effects on the pathophysiology of ASD, but the precise mechanisms related to the pathophysiology of ASD are unknown and definitive methods for prevention or treatment are lacking (Blaylock 2008) . DSM-5 proposes that ASD symptoms must appear in the early childhood (infant) (American Psychiatric Association 2013) . Receiving diagnosis at an early stage of development could contribute to the early intervention and therapy, benefiting both patients and their families (Zwaigenbaum et al. 2015; Sacrey et al. 2015; Brian et al. 2015) . However, behavioral abnormalities are often overlooked in the early stage of ASD, even experienced professionals involved in pediatric healthcare (Howlin and Asgharian 1999). Therefore, many researchers have been trying to establish quantitative diagnostic criteria that could contribute to an early and more accurate ASD diagnosis. Many interacting factors are probably contributing to the etiology of ASD, and these potential factors are described in several excellent review articles (Lam et al. 2006; Pardo and Eberhart 2007; Aoki et al. 2012; Parellada et al. 2014; Lozano et al. 2015; Rozas et al. 2015; Subramanian et al. 2015; Zhang et al. 2015; Martin et al. 2016; Muller et al. 2016; Park et al. 2016) ; this review focuses on amino acids. Neuroactive amino acids Several lines of evidence have shown that changes (e.g., availability, metabolism, and/or receptor activity) in neuroactive amino acids associated with central brain functions may play a role in the pathogenesis and/or pharmacotherapy of several psychiatric disorders (e.g., schizophrenia and mood disorders) that have symptoms, such as cognitive impairment and problems with social interactions, in common with ASD (Coyle 2006; Grant et al. 2006; Lam et al. 2006; Labrie et al. 2008; Ongür et al. 2008; Yüksel and Öngür 2010; Durrant and Heresco-Levy 2014) . 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. Due to the potential role of neuroactive amino acids in the pathogenesis and treatment of ASD, monitoring changes in their concentrations in body (...truncated)


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Hui-Fei Zheng, Wen-Qiang Wang, Xin-Min Li, Gail Rauw, Glen B. Baker. Body fluid levels of neuroactive amino acids in autism spectrum disorders: a review of the literature, Amino Acids, 2017, pp. 57-65, Volume 49, Issue 1, DOI: 10.1007/s00726-016-2332-y