Increased serum levels of glutamate in adult patients with autism
Precise mechanisms underlying the pathophysiology of autism are currently unknown. Given the major role of glutamate in brain development, we have hypothesized that glutamatergic neurotransmission plays a role in the pathophysiology of autism. In this study, we studied whether amino acids (glutamate, glutamine, glycine, D-serine, and L-serine) related to glutamatergic neurotransmission are altered in serum of adult patients with autism.
We measured serum levels of amino acids in 18 male adult patients with autism and age-matched 19 male healthy subjects using high-performance liquid chromatography.
Serum levels (mean = 89.2 microM, S.D. = 21.5) of glutamate in the patients with autism were significantly (t = -4.48, df = 35, p < 0.001) higher than those (mean = 61.1 microM, S.D. = 16.5) of normal controls. In contrast, serum levels of other amino acids (glutamine, glycine, d-serine, l-serine) in the patients with autism did not differ from those of normal controls. There was a positive correlation (r = 0.523, p = 0.026) between serum glutamate levels and Autism Diagnostic Interview-Revised (ADI-R) social scores in patients.
The present study suggests that an abnormality in glutamatergic neurotransmission may play a role in the pathophysiology of autism.
Available from: Paul C Guest
- ", 1 , 8 ↔ Serum, plasma 7 (9 studies) (D'Eufemia et al., 1995; Aldred et al., 2003; Shinohe et al., 2006; Paşca, 2009; Adams et al., 2011; Shimmura et al., 2011; Tirouvanziam et al., 2012) "
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ABSTRACT: Autism spectrum disorders (ASD) are a heterogeneous group of disorders which have complex behavioural phenotypes. Although ASD is a highly heritable neuropsychiatric disorder, genetic research alone has not provided a profound understanding of the underlying causes. Recent developments using biochemical tools such as transcriptomics, proteomics and cellular models, will pave the way to gain new insights into the underlying pathological pathways. This review addresses the state-of-the-art in the search for molecular biomarkers for ASD. In particular, the most important findings in the biochemical field are highlighted and the need for establishing streamlined interaction between behavioural studies, genetics and proteomics is stressed. Eventually, these approaches will lead to suitable translational ASD models and, therefore, a better disease understanding which may facilitate novel drug discovery efforts in this challenging field.
The International Journal of Neuropsychopharmacology 11/2013; 17(04):1-23. DOI:10.1017/S146114571300117X · 4.01 Impact Factor
Available from: PubMed Central
- "DHEA-C attained particularly high levels in the saliva of autistic children (its median concentrations reached 237, 445, 270, and 194 % of control values in groups AM I, AM II, AF I and AF II, respectively). Such excess of an excitatory steroid may amplify the neurostimulant effects resulting from reported deficits in GABA neurotransmission  and augmented activity of glutamate  in persons with autism, contributing to increased anxiety, sleep disturbances and seizures, which are often comorbid with ASDs . "
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ABSTRACT: Autism is diagnosed on the basis of behavioral manifestations, but its biomarkers are not well defined. A strong gender bias typifying autism (it is 4–5 times more prevalent in males) suggests involvement of steroid hormones in autism pathobiology. In order to evaluate the potential roles of such hormones in autism, we compared the salivary levels of 22 steroids in prepubertal autistic male and female children from two age groups (3–4 and 7–9 years old) with those in healthy controls. The steroids were analyzed using gas chromatography–mass spectrometry and radioimmunoassay. Statistical analysis (ANOVA) revealed that autistic children had significantly higher salivary concentrations of many steroid hormones (both C21 and C19) than control children. These anomalies were more prominent in older autistic children and in boys. The levels of androgens (androstenediol, dehydroepiandrosterone, androsterone and their polar conjugates) were especially increased, indicative of precocious adrenarche and predictive of early puberty. The concentrations of the steroid precursor, pregnenolone, and of several pregnanolones were also higher in autistic than in healthy children, but cortisol levels were not different. Some steroids, whose levels are raised in autism (allopregnanolone, androsterone, pregnenolone, dehydroepiandrosterone and their sulfate conjugates) are neuroactive and modulate GABA, glutamate, and opioid neurotransmission, affecting brain development and functioning. These steroids may contribute to autism pathobiology and symptoms such as elevated anxiety, sleep disturbances, sensory deficits, and stereotypies among others. We suggest that salivary levels of selected steroids may serve as biomarkers of autism pathology useful for monitoring the progress of therapy.
Electronic supplementary material
The online version of this article (doi:10.1007/s00787-013-0472-0) contains supplementary material, which is available to authorized users.
European Child & Adolescent Psychiatry 09/2013; 23(6). DOI:10.1007/s00787-013-0472-0 · 3.34 Impact Factor
Available from: Ahmad Ghanizadeh
- "Decreased in plasma [8, 16, 17, 21] Lysine Increased in plasma [8, 10, 16] No difference in plasma  Tryptophan Decreased in plasma [16, 17] Taurine Decreased in plasma  Increased in plasma [15, 22] Homocysteine Increased in serum [16, 23] Increased total homocysteine (tHcy) in serum  Decreased plasma levels of homocysteine  Increased level in urine  Citrulline Decreased in plasma  Alanine No difference in plasma  Increased in plasma  Glycine No difference in plasma  Valine Decreased in plasma [8, 16] No difference in plasma  Aspartic acid Decreased platelet levels  GABA Decreased platelet levels  Arginine No difference in plasma  Isoleucine Decreased  Threonine Decreased in plasma  Serine Decreased in plasma  Proline No difference in plasma  Asparagine Decreased in plasma [15, 17] Increased in plasma  Aspartic acid No difference in plasma  Methionine Increased in plasma  Decreased  Glycine No difference in serum level  D-serine No difference in serum level  L-serine No difference in serum level  Glutamic acid Increased in plasma [10, 16, 17] Decreased platelet levels  Glutamate Increased level in plasma [9, 10, 15, 19, 28] Increased in some regions of brain  Aspartate Increased in plasma  Phenylalanine Decreased in plasma   Increased in plasma  Glutamine Decreased in plasma [9, 10, 15–17] No difference in serum level  Decreased platelet levels  Lysine Increased in plasma  Tyrosine Decreased in plasma   Increased in plasma  its higher level is a compensatory phenomenon for the increased glutamate level . Nevertheless, others reported that the mean level of taurine is decreased in autism  "
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ABSTRACT: There are many reports about the significant roles of some amino acids in neurobiology and treatment of autism. This is a critical review of amino acids levels in autism. No published review article about the level of amino acids in autism was found. The levels of glutamate and homocystein are increased in autism while the levels of glutamine and tryptophan are decreased. Findings regarding the plasma levels of taurine and lysine are controversial. The urinary levels of homocysteine and essential amino acids in both the untreated and treated autistic children are significantly less than those in the controls. The current literature suffers from many methodological shortcomings which needed to be considered in future studies. Some of them are age, gender, developmental level, autism symptoms severity, type of autism spectrum disorders, medical comorbidities, intelligent quotient, diet, concomitant medications, body mass index, and technical method of assessment of amino acids.
Disease markers 09/2013; 35(5):281-286. DOI:10.1155/2013/536521 · 1.56 Impact Factor
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