Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

6R-L-erythro-5, 6, 7, 8-Tetrahydrobiopterin (6R-BH4) is known as a cofactor for the hydroxylases of phenylalanine, tyrosine and tryptophan and also as a cofactor for nitric oxide synthase. Recently, a novel function of 6R-BH4 has been found: that is, 6R-BH4 acts on specific membrane receptors to directly stimulate the release of monamine neurotransmitters such as dopamine and serotonin, independently of its cofactor activity. In addition, it indirectly stimulates the release of non-monoamine neurotransmitters such as acetylcholine and glutamate, through activation of monoaminergic systems. In this paper, we briefly review recent experimental data, which provide new insights into the role of 6R-BH4 as a regulator of neuronal function. We also discuss the possibility of treatment by 6R-BH4 of neuropsychiatric diseases such as Parkinson's disease, Alzheimer's disease, depression and infantile autism.
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PMID:[A novel function of tetrahydrobiopterin]. 136 Nov 76

Urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion in two consecutive collection periods (5:00 PM-11:00 PM and 11:00 PM-8:00 AM) and whole blood serotonin (5-HT) and tryptophan (TRP) were measured in groups of unmedicated autistics (n = 16), medicated autistics (n = 20), and normal controls (n = 27). Whole blood 5-HT values were significantly higher in unmedicated autistics compared to normal controls. No significant differences were found in 5-HIAA excretion (microgram/mg creatinine, mean +/- SD) between unmedicated autistics (4.07 +/- 1.52) and normal controls (3.50 +/- 1.07), or between medicated (5.35 +/- 2.93) and drug-free autistic individuals. No correlations were found between 5-HT values and urinary 5-HIAA excretion. Urinary 5-HIAA (microgram/mg creatinine, mean +/- SD) was significantly greater in hyperserotonemic autistic subjects (4.88 +/- 0.87) compared to normal controls (3.50 +/- 1.07, total collection period; p = 0.002). The relevance of these findings to the possibility that increased gut production of 5-HT might cause the elevated whole blood 5-HT levels seen in autism is discussed.
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PMID:Urinary 5-hydroxyindoleacetic acid and whole blood serotonin and tryptophan in autistic and normal subjects. 244 Apr 83

The serotonin metabolism was extensively studied in 22 couples of autistic children and age- and sex-matched controls. Histamine, calcium, and uric acid were also measured in urine and whole blood or plasma. Autistics and controls did not differ in histamine, and only minor changes were noticed in calcium content. According to previous reports, serotonin levels were often, but not always, elevated in the blood of autistic children. Based on data including urinary serotonin and 5-hydroxyindoleacetic acid, platelet serotonin uptake and efflux, platelet monoamine oxidase and glutathione peroxidase activities, and uric acid and plasma tryptophan, the origin(s) of such hyperserotonemia in autism appear(s) to be of metabolic origin, i.e., a decreased catabolism and/or an increased biosynthesis of serotonin.
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PMID:Serotonin metabolism and other biochemical parameters in infantile autism. A controlled study of 22 autistic children. 246 21

A new method for measurement of the turnover rate of aromatic amino acids and related compounds in vivo using stable isotopes was developed. Deuterium-and carbon 13-labeled phenylalanine and deuterium-labeled tryptophan were used as tracers. This method was applied for the analysis of amino acid and amine metabolism in infantile autism. Marked disturbances of uptake of deuterated phenylalanine and tryptophan from intestine into blood were found in a portion of autistic patients (group A). In another group of the patients a remarkable decrease of turnover of tyrosine in blood was found (group B). This phenomenon was confirmed by an experiment using carbon 13 labeled phenylalanine. These findings might suggest that supply of tyrosine and free tryptophan to the brain (in group A) or supply of tyrosine (group B) to the brain might be decreased. We postulated that in some of autistic patients there might exist decreases in synthesis of catecholamine or serotonin. Based on the hypothesis, we started a new treatment with L-DOPA and 5 HTP in small doses, and found significant effects in some patients. However, in some, the amino acids caused marked aggravation of the symptoms. Recently, Hayaishi and his colleagues reported that R-tetrahydrobiopterin (R-THBP) could enhance biosynthesis of catecholamine and serotonin in the brain. Therefore, we started a clinical trial concerning effects of R-THBP. In the beginning, 17 cases were treated and patients younger than 5 years old showed marked improvement. Then, a double blind trial with inactive placebo was performed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Metabolic changes in aromatic amino acids and monoamines in infantile autism and development of new treatment related to the finding]. 265 86

Whole blood serotonin (5-HT) was significantly increased in a drug-free autistic group (n = 17) compared to age- and sex-matched normal control (n = 20). Blood tryptophan (TRP) values and platelet counts were similar in unmedicated autistics and normal subjects; but whole blood concentrations of TRP were significantly lower, and 5-HT values tended to be lower in the medicated group compared to unmedicated autistics. Highly significant intraclass correlation coefficients and low mean percentage differences were found for repeated measures over a year's period of whole blood 5-HT and the platelet count in the unmedicated but not in the medicated group. Blood TRP values were highly variable over time in both the medicated and drug-free autistic groups.
J Autism Dev Disord 1989 Mar
PMID:Whole blood serotonin and tryptophan in autism: temporal stability and the effects of medication. 270 96

In this controlled study of 22 autistic children and 22 normal controls matched for age and sex, the frequency of hyperserotonemia in infantile autism was confirmed. Platelet serotonin was elevated in patients. Comparative to controls, serotonin was also high in urine of autistic patients, while, on the contrary there was no difference for the urinary excretion of 5-HIAA. No difference was observed either for serotonin uptake and efflux or for MAO activity, in isolated platelets. The elevation of plasma free tryptophan - significant only with the Kolmogorov Smirnov test - suggests that 5-HT biosynthesis might be enhanced. In the group of patient reported in this study, disorders of serotonin metabolism are associated with disturbances of platelet catecholamines, and also with elevated immunoglobulins and enhanced cellular immunity reactions.
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PMID:[Metabolism of serotonin in autism in children]. 306 46

Whole blood serotonin and tryptophan were measured in 87 normal subjects and in 40 autistic subjects. Whole blood serotonin concentrations (mean +/- SE) were significantly higher in drug-free (N = 21) autistics (205 +/- 16 ng/ml) than in normals (136 +/- 5.4 ng/ml). The Gaussian distribution of serotonin levels in the unmedicated autistic group suggests the elevation was not due to a subgroup of autistic subjects. Autistics medicated with anticonvulsants or neuroleptics had significantly lower serotonin levels than did drug-free autistic subjects. Whole blood tryptophan levels and platelet counts were similar in the autistic and normal groups. The possible causes of the hyperserotonemia of autism are discussed.
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PMID:Whole blood serotonin in autistic and normal subjects. 343 95

The plasma free and total tryptophan (TRP) and blood serotonin levels in autistic children were examined simultaneously in order to establish a relationship between these parameters and the pathophysiology of infantile autism. The subjects were 37 autistic children, 28 normal adults and 12 normal children. Quantitative evaluation of the global severity, hyperkinetic behavior and intellectual function was performed by means of the Children's Psychiatric Rating Scale (CPRS-1), the Werry-Weiss-Peters Activity Scale (WWPAS) and the Developmental Quotient (DQ), respectively. The mean total TRP level in autistic children was not significantly different from those in normal children and adults. The mean plasma free TRP level in autistic children was significantly higher than those in normal children and adults. A significant positive correlation was found between the plasma free TRP level and CPRS-1 or WWPAS score in autistic children. Moreover, there tended to be a negative correlation between the plasma free TRP level and DQ. These findings suggest the presence of some defect in the metabolic system for TRP-serotonin in the brain of autistic children.
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PMID:Plasma free tryptophan concentration in autistic children. 379 12

In 37 autistic children and 67 normal control subjects, determinations of plasma free and total tryptophan and blood serotonin levels were made simultaneously in order to establish a relationship between these parameters and the clinical rating scales: Children's Psychiatric Rating Scale (CPRS-1), Werry-Weiss-Peters Activity Scale (WWPAS), and Developmental Quotient (DQ). The plasma free tryptophan level was significantly higher in autistic children than in normal control subjects. There tended to be a significant positive correlation between the plasma free tryptophan level and CPRS-1 or WWPAS score and a negative correlation between the plasma free tryptophan level and DQ. The blood serotonin level was significantly higher in autistic children than in normal control subjects. No correlation was established, however, between the blood serotonin level and CPRS-1, WWPAS score or DQ, and hence the clinical symptoms. Nor was there a correlation between blood serotonin and free tryptophan levels in these children. These results suggest that autistic children have some defect in tryptophan-serotonin metabolism in the brain, which is responsible for the clinical manifestations and behavioral abnormalities of infantile autism.
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PMID:Blood serotonin and free tryptophan concentration in autistic children. 620 48

This is a report on recent developments in pediatric psychopharmacology: new drugs and new applications for established drugs. The drugs reviewed include imipramine, amitryptiline, lithium, piracetam, propranolol, tryptophan, clonidine, pyridoxine and fenfluramine. Putative indications include prepubertal depression, school phobia, anorexia nervosa, explosive-aggressive behavior, learning disabilities, attention deficit disorder (hyperactivity), Tourette's syndrome, autism, and the Lesch-Nyhan syndrome. Some of the information presented in this report must be regarded as "preliminary," and caution is advised in its interpretation and application.
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PMID:New developments in pediatric psychopharmacology. 635 89


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