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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In infantile autism, the serotoninergic (5-HT) hypothesis is corroborated by biological dosages and therapeutic effects of fenfluramine which decrease blood serotonin. However other drugs, such as dopaminergic agonists or antagonists, have therapeutic effects. Therefore, we tested the hypothesis that two dopaminergic (DA) drugs have a similar 5-HT effect underlying the therapeutic efficiency. We evaluated in a randomized, double-blind and cross-over study, the effects of a DA agonist (bromocriptine) and a DA antagonist (amisulpride) on platelet 5-HT in infantile autism. The prolactinemia, reflecting the DA action, has been also measured. Nine children, aged from 4 to 13 years, according to the DSM III for infantile autism, received either drug in a random order during four weeks with an in-between placebo period of six weeks. The dosages of platelet 5-HT and serum prolactin were carried out at the beginning and at the end of every phase of treatment (active or placebo) with radioenzymology and radioimmunoassay methods respectively. The principal results on serum prolactin show neither order x treatment interaction, nor order effect but a significant treatment effect (p < 0.01): amisulpride increases serum prolactin whereas bromocriptine decreases according to the usual data. About platelet 5-HT, there is neither order x treatment interaction, nor treatment effect but a significant order effect (p < 0.01). Both drugs increase platelet 5-HT in the first phase of treatment. This order effect could be explained by a remanent effect of amisulpride after 6 wash-out weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Platelet serotonin in infantile autism. Cross-over effects of a dopamine agonist and an antagonist]. 136 54

The neurochemistry of autism, the most well-validated childhood neuropsychiatric disorder, has been studied extensively over the past three decades. Autism is of interest neurochemically because it represents a relatively homogeneous disorder with a triad of social, communicative, and intellectual developmental disturbance. Because a sufficient animal model has been lacking and relatively few diagnosed people with autism have died, most investigation has been of peripheral fluids and tissues. The most consistent finding has been that over 25% of autistic children and adolescents are hyperserotonemic. However, after 29 years of investigation, the mechanism of hyperserotonemia has not been determined. Hyperserotonemia has been found to be familial. Elevated plasma norepinephrine has also been a replicated finding. Cerebrospinal fluid (CSF) opiate activity has been found to be elevated in two studies. Plasma cyclic adenosine monophosphate (cAMP) has been found to be elevated in autistic children. A high rate of nonsuppression after dexamethasone and blunted or delayed growth hormone response to L-dopa have been found. Abnormal cell-mediated immunity has been replicated consistently in autism. Although several pharmacological trials have been conducted and shown promise in initial open trials, only "typical" antipsychotic drugs have shown replicable chronic ameliorating effects in double-blind trials. However, chronic neurotoxicity (tardive dyskinesia) has also been revealed. Findings of morphological changes in the cerebellum have been replicated. Findings in need of replication include diminished platelet function, increased baseline CSF homovanillic acid, decreased nerve cell adhesion molecule serum fragment, blunted prolactin response to fenfluramine, amelioration of symptoms by naltrexone and bromocriptine, reduced electroretinographic (ERG) b-wave amplitude, and morphological changes in the hippocampus, amygdala, and septal nuclei. In addition to refining and replicating past findings, future directions that may be fruitful include investigation of neurochemical aspects of platelet function, of interactions between monoaminergic systems, of phosphatidylinositides, and of pharmacological response to "atypical" antipsychotic agents and relatively selective serotonin receptor subtype agonists or antagonists.
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PMID:Autism: review of neurochemical investigation. 170 Apr 86

Altered serotonergic function has been postulated to exist in autistic disorder. Central serotonergic responsivity was assessed with a neuroendocrine challenge test in seven male young adults with autistic disorder and in seven age- and gender-matched healthy controls. Binding indexes and physiologic responsivity of the platelet serotonin-2 (5-HT2) receptor complex were also measured, as was whole-blood serotonin content. Compared with controls, autistic subjects had substantially blunted prolactin release in response to a 60-mg oral dose of fenfluramine hydrochloride, an indirect serotonin agonist [corrected]. Furthermore, the magnitude of serotonin-amplified platelet aggregation, mediated by the platelet 5-HT2 receptor complex, was reduced in the autistic group, as was the mean number of platelet 5-HT2 receptor sites. Among autistic subjects, fenfluramine-induced prolactin release correlated positively with the serotonin-amplified platelet aggregation response and negatively with whole-blood serotonin content. The results of the present study are compatible with the hypothesis that central serotonergic responsivity is decreased in male autistic young adults. Correlations between central and peripheral serotonergic measures in autistic subjects suggest that systemic alterations in serotonergic function may occur in autism.
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PMID:Serotonergic responsivity in male young adults with autistic disorder. Results of a pilot study. 291 50

An abnormal circadian pattern of melatonin was found in a group of young adults with an extreme autism syndrome. Although not out of phase, the serum melatonin levels differed from normal in amplitude and mesor. Marginal changes in diurnal rhythms of serum TSH and possibly prolactin were also recorded. Subjects with seizures tended to have an abnormal pattern of melatonin correlated with EEG changes. In others, a parallel was evidenced between thyroid function and impairment in verbal communication. There appears to be a tendency for various types of neuroendocrinological abnormalities in autistics, and melatonin, as well as possibly TSH and perhaps prolactin, could serve as biochemical variables of the biological parameters of the disease.
J Autism Dev Disord 1995 Dec
PMID:Brief report: circadian melatonin, thyroid-stimulating hormone, prolactin, and cortisol levels in serum of young adults with autism. 872 32

Blood concentrations of pituitary hormones adrenocorticotropin (ACTH), prolactin, growth hormone, and adrenal hormone-cortisol were measured in 36 autistic and 27 control individuals. Individuals with autism had significantly lower serum concentrations of cortisol (p < 10(-6)), and significantly higher concentrations of ACTH (p = 0.002) than control age- and sex-matched subjects. Also, prolactin concentrations in autistic patients with epilepsy were significantly higher when compared with normal subjects. The observed hormonal changes may indicate dysfunction of the hypothalamo-pituitary-adrenal axis in individuals with autism.
J Autism Dev Disord 2003 Aug
PMID:Lower cortisol and higher ACTH levels in individuals with autism. 1295 23

Autism is a neurodevelopmental disorder characterized by dysfunction in three primary behavioural domains: repetitive behaviours, social deficits, and language abnormalities. There is evidence that abnormalities exist in the serotonin (5-HT) system in autism spectrum patients. Furthermore, 5-HT is known to play a role in repetitive and social behaviours. This study examined the effect of m-chlorophenylpiperazine (m-CPP) on repetitive behaviours and prolactin response in 11 adults with autism or Aspergers disorder and 8 age- and gender-matched healthy controls via randomized double-blind, m-CPP and placebo challenges. The primary outcome measure was an instrument rating six repetitive behaviours: need to know, repeating, ordering, need to tell/ask, self-injury, and touching. Patients with autism spectrum disorders showed a significant increase in repetitive behaviours at end-point following oral m-CPP in comparison to placebo. Additionally subjects with autism spectrum disorders showed a significantly increased prolactin response to m-CPP compared to normal controls, with neither group responding to placebo. This study provides further evidence for altered 5-HT sensitivity in individuals with autism spectrum disorders, as well as a possible relationship between repetitive behaviours in autism spectrum disorders and abnormalities in the 5-HT system.
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PMID:Increased repetitive behaviours and prolactin responsivity to oral m-chlorophenylpiperazine in adults with autism spectrum disorders. 1513 62

Some studies have suggested that disorders in the central serotonergic function may play a role in the pathophysiology of autistic disorder. In order to assess the central serotonergic turnover in autism, this study examines the cortisol and prolactin responses to administration of L-5-hydroxy-tryptophan (5-HTP), the direct precursor of 5-HT in 18 male, post-pubertal, Caucasian autistic patients (age 13-19 y.; I.Q.>55) and 22 matched healthy volunteers. Serum cortisol and prolactin were determined 45 and 30 minutes before administration of 5-HTP (4 mg/kg in non enteric-coated tablets) or an identical placebo in a single blind order and, thereafter, every 30 minutes over a 3-hour period. The 5-HTP-induced increases in serum cortisol were significantly lower in autistic patients than in controls, whereas there were no significant differences in 5-HTP-induced prolactin responses between both study groups. In baseline conditions, no significant differences were found in serum cortisol and prolactin between autistic and normal children. The results suggest that autism is accompanied by a central serotonergic hypoactivity and that the latter could play a role in the pathophysiology of autism.
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PMID:Central serotonergic hypofunction in autism: results of the 5-hydroxy-tryptophan challenge test. 1769 83

Little has been reported on the factors, genetic or other, that underlie the variability in individual response, particularly for autism. In this study we simultaneously explored the effects of multiple candidate genes on clinical improvement and occurrence of adverse drug reactions, in 45 autistic patients who received monotherapy with risperidone up to 1 year. Candidate genes involved in the pharmacokinetics (CYP2D6 and ABCB1) and pharmacodynamics (HTR2A, HTR2C, DRD2, DRD3, HTR6) of the drug, and the brain-derived neurotrophic factor (BDNF) gene, were analysed. Using the generalized estimating equation method these genes were tested for association with drug efficacy, assessed with the Autism Treatment Evaluation Checklist, and with safety and tolerability measures, such as prolactin levels, body mass index (BMI), waist circumference and neurological adverse effects, including extrapyramidal movements. Our results confirm that risperidone therapy was very effective in reducing some autism symptoms and caused few serious adverse effects. After adjusting for confounding factors, the HTR2A c.-1438G>A, DRD3 Ser9Gly, HTR2C c.995G>A and ABCB1 1236C>T polymorphisms were predictors for clinical improvement with risperidone therapy. The HTR2A c.-1438G>A, HTR2C c.68G>C (p.C33S), HTR6 c.7154-2542C>T and BDNF c.196G>A (p.V66M) polymorphisms influenced prolactin elevation. HTR2C c.68G>C and CYP2D6 polymorphisms were associated with risperidone-induced increase in BMI or waist circumference. We thus identified for the first time several genes implicated in risperidone efficacy and safety in autism patients. Although association results require replication, given the small sample size, the study makes a preliminary contribution to the personalized therapy of risperidone in autism.
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PMID:Pharmacogenetics of risperidone therapy in autism: association analysis of eight candidate genes with drug efficacy and adverse drug reactions. 1999 80

A systematic review and meta-analysis were performed examining the efficacy of aripiprazole for the treatment of irritability associated with autistic disorder in children and adolescents. Aripiprazole was found to be more effective in reducing irritability compared with placebo at 8 weeks, SMD -0.64 [-0.90 to -0.39, P < 0.00001] as determined by the Aberrant Behaviour Checklist irritability subscale (ABC-I). Pooled data from two eight week trials show that sedation is the most commonly reported adverse event. Statistically significant weight gain was also associated with aripiprazole, but there was a decrease in serum prolactin. Most adverse effects were deemed to be mild to moderate in severity. Four open trials and three case series all show support for aripiprazole in reducing the behavioural symptoms of autism. Long-term studies are required to determine the efficacy and safety of aripiprazole in autistic disorder in children.
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PMID:Aripiprazole: a review of its use in the treatment of irritability associated with autistic disorder patients aged 6-17. 2386 44

Social stressors such as depressed maternal care and family conflict are robust challenges which can have long-term physiological and behavioral effects on offspring and future generations. The current study investigates the transgenerational effects of an ethologically relevant chronic social stress on the behavior and endocrinology of juvenile and adult rats. Exposure to chronic social stress during lactation impairs maternal care in F0 lactating dams and the maternal care of the F1 offspring of those stressed F0 dams. The overall hypothesis was that the male and female F2 offspring of stressed F1 dams would display decreased social behavior as both juveniles and adults and that these behavioral effects would be accompanied by changes in plasma corticosterone, prolactin, and oxytocin. Both the female and male F2 offspring of dams exposed to chronic social stress displayed decreased social behavior as juveniles and adults, and these behavioral effects were accompanied by decreases in basal concentrations of corticosterone in both sexes, as well as elevated juvenile oxytocin and decreased adult prolactin in the female offspring. The data support the conclusion that social stress has transgenerational effects on the social behavior of the female and male offspring which are mediated by changes in the hypothalamic-pituitary-adrenal axis and hypothalamic-pituitary-gonadal axis. Social stress models are valuable resources in the study of the transgenerational effects of stress on the behavioral endocrinology of disorders such as depression, anxiety, autism, and other disorders involving disrupted social behavior.
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PMID:Transgenerational effects of social stress on social behavior, corticosterone, oxytocin, and prolactin in rats. 2465 20


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