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)

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

In most cases symptoms of autism begin in early infancy. However, a subset of children appears to develop normally until a clear deterioration is observed. Many parents of children with "regressive"-onset autism have noted antecedent antibiotic exposure followed by chronic diarrhea. We speculated that, in a subgroup of children, disruption of indigenous gut flora might promote colonization by one or more neurotoxin-producing bacteria, contributing, at least in part, to their autistic symptomatology. To help test this hypothesis, 11 children with regressive-onset autism were recruited for an intervention trial using a minimally absorbed oral antibiotic. Entry criteria included antecedent broad-spectrum antimicrobial exposure followed by chronic persistent diarrhea, deterioration of previously acquired skills, and then autistic features. Short-term improvement was noted using multiple pre- and post-therapy evaluations. These included coded, paired videotapes scored by a clinical psychologist blinded to treatment status; these noted improvement in 8 of 10 children studied. Unfortunately, these gains had largely waned at follow-up. Although the protocol used is not suggested as useful therapy, these results indicate that a possible gut flora-brain connection warrants further investigation, as it might lead to greater pathophysiologic insight and meaningful prevention or treatment in a subset of children with autism.
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PMID:Short-term benefit from oral vancomycin treatment of regressive-onset autism. 1139 29

There is growing awareness that primary gastrointestinal pathology may play an important role in the inception and clinical expression of some childhood developmental disorders, including autism. In addition to frequent gastrointestinal symptoms, children with autism often manifest complex biochemical and immunological abnormalities. The gut-brain axis is central to certain encephalopathies of extra-cranial origin, hepatic encephalopathy being the best characterized. Commonalities in the clinical characteristics of hepatic encephalopathy and a form of autism associated with developmental regression in an apparently previously normal child, accompanied by immune-mediated gastrointestinal pathology, have led to the proposal that there may be analogous mechanisms of toxic encephalopathy in patients with liver failure and some children with autism. Aberrations in opioid biochemistry are common to these two conditions, and there is evidence that opioid peptides may mediate certain aspects of the respective syndromes. The generation of plausible and testable hypotheses in this area may help to identify new treatment options in encephalopathies of extra-cranial origin. Therapeutic targets for this autistic phenotype may include: modification of diet and entero-colonic microbial milieu in order to reduce toxin substrates, improve nutritional status and modify mucosal immunity; anti-inflammatory/immunomodulatory therapy; and specific treatment of dysmotility, focusing, for example, on the pharmacology of local opioid activity in the gut.
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PMID:Review article: the concept of entero-colonic encephalopathy, autism and opioid receptor ligands. 1192 83

Autism is a collection of behavioral symptoms characterized by dysfunction in social interaction and communication in affected children. It is typically associated with restrictive, repetitive, and stereotypic behavior and manifests within the first 3 years of life. The cause of this disorder is not known. Over the past decade, a significant upswing in research has occurred to examine the biologic basis of autism. Recent clinical studies have revealed a high prevalence of gastrointestinal symptoms, inflammation, and dysfunction in children with autism. Mild to moderate degrees of inflammation were found in both the upper and lower intestinal tract. In addition, decreased sulfation capacity of the liver, pathologic intestinal permeability, increased secretory response to intravenous secretin injection, and decreased digestive enzyme activities were reported in many children with autism. Treatment of digestive problems appears to have positive effects on autistic behavior. These new observations represent only a piece of the unsolved autism "puzzle" and should stimulate more research into the brain-gut connection.
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PMID:Autism and gastrointestinal symptoms. 1201 Jun 27

A dietitian discusses the theory that peptides with opioid activity may cause or trigger autism. The use of an exclusion diet to treat autism is explained, weighing the potential benefits against some of the practical difficulties of keeping to a strict exclusion diet. The use of nutritional supplements is described. An abnormal gut flora has also been implicated in autism and the use of probiotics and prebiotics in improving the integrity of the gut mucosa is also discussed.
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PMID:Diet in autism and associated disorders. 1241 51

Autism and allied autistic spectrum disorders (ASD) present myriad behavioral, clinical, and biochemical abnormalities. Parental participation, advanced testing protocols, and eclectic treatment strategies have driven progress toward cure. Behavioral modification and structured education are beneficial but insufficient. Dietary restrictions, including removal of milk and other casein dairy products, wheat and other gluten sources, sugar, chocolate, preservatives, and food coloring are beneficial and prerequisite to benefit from other interventions. Individualized IgG or IgE testing can identify other troublesome foods but not non-immune mediated food sensitivities. Gastrointestinal improvement rests on controlling Candida and other parasites, and using probiotic bacteria and nutrients to correct dysbiosis and decrease gut permeability. Detoxification of mercury and other heavy metals by DMSA/DMPS chelation can have marked benefit. Documented sulfoxidation-sulfation inadequacies call for sulfur-sulfhydryl repletion and other liver p450 support. Many nutrient supplements are beneficial and well tolerated, including dimethylglycine (DMG) and a combination of pyridoxine (vitamin B6) and magnesium, both of which benefit roughly half of ASD cases. Vitamins A, B3, C, and folic acid; the minerals calcium and zinc; cod liver oil; and digestive enzymes, all offer benefit. Secretin, a triggering factor for digestion, is presently under investigation. Immune therapies (pentoxifyllin, intravenous immunoglobulin, transfer factor, and colostrum) benefit selected cases. Long-chain omega-3 fatty acids offer great promise. Current pharmaceuticals fail to benefit the primary symptoms and can have marked adverse effects. Individualized, in-depth clinical and laboratory assessments and integrative parent-physician-scientist cooperation are the keys to successful ASD management.
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PMID:Autism, an extreme challenge to integrative medicine. Part 2: medical management. 1249 73

Opioid peptides derived from food proteins (exorphins) have been found in urine of autistic patients. Based on the work of several groups, we try to show that exorphins and serotonin uptake stimulating factors may explain many of the signs and symptoms seen in autistic disorders. The individual symptoms ought to be explainable by the properties and behavioural effects of the found peptides. The data presented form the basis of an autism model, where we suggest that exorphins and serotonin uptake modulators are key mediators for the development of autism. This may be due to a genetically based peptidase deficiency in at least two or more peptidases and, or of peptidase regulating proteins made manifest by a dietary overload of exorphin precursors such as by increased gut uptake.
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PMID:Can the pathophysiology of autism be explained by the nature of the discovered urine peptides? 1260 33

In a subgroup of children with autism-spectrum like conditions symptoms seem to appear as a 'regression' (in normal development). It has been postulated that the onset of such autistic symptoms may involve an autoimmune response against the central nervous system and that the antigenic determinant could possibly be gastrointestinal in origin. It has been suggested that the presence of the measles virus and 'autistic enterocolitis' demonstrates the possibility that the MMR triple vaccine may be mediating the inflammation with possible production of antibodies against the virus containing vaccine. Such an antibody may share antigenic determinant to molecules found in the gut. We propose that this may be secretin or its receptor, found in the gut as well as in the central nervous system. The antibody response to the gut may also conceivably occur in the brain at a critical time in development. The modulation of development by secretin may be a static event possibly occurring at a specific time in early childhood development and if it involves an autoimmune response then a disruption in development may result. These hypothesized events can only occur if the MMR vaccine shares antigenic determinants that resemble secretin or any of its receptor types and remains to be studied.
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PMID:Does the MMR vaccine and secretin or its receptor share an antigenic epitope? 1271 Aug 97

Autism is a life-long developmental disorder affecting as many as 1 in 500 children. The causes for this profound disorder are largely unknown. Recent research has uncovered pathology in the gastrointestinal tract of autistic children. The pathology, reported to extend from the esophagus to the colon, is described here along with other studies pointing to a connection between diet and the severity of symptoms expressed in autism. The evidence that there is impaired intestinal permeability in autism is reviewed, and various theories are discussed by which a leaky gut could develop. Lastly, some possible ways in which impaired gastrointestinal function might influence brain function are discussed.
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PMID:Intestinal pathophysiology in autism. 1277 94

The recent suggestion that secretin may be useful in treating autism and schizophrenia has begun to focus attention on the mechanisms underlying this gut-brain peptide's actions in the central nervous system (CNS). In vitro autoradiographic localization of (125)I-secretin binding sites in rat brain shows the highest binding density in the nucleus tractus solitarius (NTS). Recent evidence suggests that intravenous infusion of secretin causes fos activation in NTS, a relay station playing important roles in the central regulation of autonomic functions. In this study, whole cell patch-clamp recordings were obtained from 127 NTS neurons in rat medullary slices. The mean resting membrane potential of these neurons was -54.7 +/- 0.3 mV, the mean input resistance was 3.7 +/- 0.2 GOmega, and the action potential amplitude of these neurons was always >70 mV. Current-clamp studies showed that bath application of secretin depolarized the majority (80.8%; 42/52) of NTS neurons tested, whereas the remaining cells were either unaffected (17.3%; 9/52) or hyperpolarized (1.9%; 1/52). These depolarizing effects were maintained in the presence of 5 microM TTX and found to be concentration dependent from 10(-12) to 10(-7) M. Using voltage-clamp techniques, we also identified modulatory actions of secretin on specific ion channels. Our results demonstrate that while secretin is without effect on net whole cell potassium currents, it activates a nonselective cationic conductance (NSCC). These results show that NTS neurons are activated by secretin as a consequence of activation of a NSCC and support the emerging view that secretin can act as a neuropeptide within the CNS.
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PMID:Secretin depolarizes nucleus tractus solitarius neurons through activation of a nonselective cationic conductance. 1471 95


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