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

We report a 12 month double-blind randomized crossover trial of fenfluramine in 20 children with the syndrome of autism. On active drug most of the children lost weight and blood serotonin levels fell by an average of 60%. There was a fall in urinary dopamine (DA) and noradrenaline (NA) levels and increased excretion of homovanillic acid (HVA). Some of the children showed improvement in tests of cognitive and language function, although the results did not achieve overall statistical significance. Event-related brain potentials (ERPs) were obtained in seven subjects on an auditory choice reaction time task. Side effects of the drug included irritability and lethargy. Fenfluramine may have a limited place in the management of some patients with autistic disorder.
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PMID:A controlled crossover trial of fenfluramine in autism. 219 54

This is a single-case report of the syndrome of Tourette's disorder (GTS) and infantile autism (IA) occurring together. Neuroleptics were not administered prior to the onset of GTS. The heuristic value of comparing the different biochemical mechanisms of the syndromes and its implication for diagnosis and etiology is discussed. Norepinephrine is thought to be at least one transmitter that differentiates the syndromes.
J Autism Dev Disord 1982 Dec
PMID:Coincidence of Tourette's disorder and infantile autism. 613 Oct 60

According to monoaminergic hypothesis of psychosis, several symptoms observed in child autism may be related to anomalies of cerebral amines and/or synaptic dysfunctioning. The main amines concerned are serotonin and dopamine which are synthetized and catabolized following similar schemes. Methyl-indolamines production, mentioned in adult schizophrenia, has not been observed in child autism. Similarly, monoaminoxydase diminution has been observed in adults and not in children. Hyperserotoninemia does exist in some cases of child autism. Results concerning dopaminergic systems are more promising. The autistic behavioral syndrome suggests a dopaminergic dysfunctioning. Enhancement of homovanillic acid, the main metabolite of dopamine, has been found both in cerebrospinal fluid and in urines of some autistic children. Moreover, modifications of dopamine-beta-hydroxylase, an enzyme that changes dopamine into noradrenaline, have been mentioned in some cases of autism. A better definition of the autistic clinical syndromes associated with a more systematic study of monoamines plasmatic and urinary derivates will allow, in the near future, a better understanding of child autism and a clearer definition of therapeutic indications.
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PMID:[Monoamine and monoamine enzyme abnormalities in childhood autism]. 631 36

A neurochemical assessment of noradrenergic and adrenergic functioning was carried out with autistic patients and normal control individuals. Norepinephrine and related compounds were measured in autistic (n = 17 unmedicated, 23 medicated; age range 9-29 years old) and normal controls (n = 27; age range 9-36 years old). Plasma levels and urinary excretion of 3-methoxy-4-hydroxy-phenylglycol (MHPG) were measured, as were urinary excretion rates of norepinephrine (NE), epinephrine (EPI), and vanillylmandelic acid (VMA). No significant group mean differences were seen between the autistic and control groups. In both the autistic and control groups urinary excretion rates of norepinephrine and epinephrine were substantially higher in the afternoon-evening (5-11 PM) compared to the overnight (11 PM-7 AM) collection period. Based on our neurochemical assessment, marked abnormalities in basal noradrenergic functioning do not appear to be present in autism.
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PMID:Noradrenergic and adrenergic functioning in autism. 798 88

Some studies have suggested that disorders in the peripheral and central metabolism of serotonin (5-HT) and noradrenaline may play a role in the pathophysiology of autistic disorder. This study examines serotonergic and noradrenergic markers in a study group of 13 male, post-pubertal, caucasian autistic patients (age 12-18 y; I.Q. > 55) and 13 matched volunteers. [3H]-paroxetine binding Kd values were significantly higher in patients with autism than in healthy volunteers. Plasma concentrations of tryptophan, the precursor of 5-HT, were significantly lower in autistic patients than in healthy volunteers. There were no significant differences between autistic and normal children in the serum concentrations of 5-HT, or the 24-hr urinary excretion of 5-hydroxy-indoleacetic acid (5-HIAA), adrenaline, noradrenaline, and dopamine. There were no significant differences in [3H]-rauwolscine binding Bmax or Kd values, or in the serum concentrations of tyrosine, the precursor of noradrenaline, between both study groups. There were highly significant positive correlations between age and 24-hr urinary excretion of 5-HIAA and serum tryptophan. The results suggest that: 1) serotonergic disturbances, such as defects in the 5-HT transporter system and lowered plasma tryptophan, may play a role in the pathophysiology of autism; 2) autism is not associated with alterations in the noradrenergic system; and 3) the metabolism of serotonin in humans undergoes significant changes between the ages of 12 and 18 years.
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PMID:Peripheral markers of serotonergic and noradrenergic function in post-pubertal, caucasian males with autistic disorder. 1069 55

alpha(2) adrenergic receptors are activated by adrenaline and noradrenaline, and three subtypes (ie, A, B, C) have differential affinities for antagonists and medications. The alpha(2c) adrenergic receptor (ADRA2C), located on chromosome 4p16.3, is a candidate gene for schizophrenia because it binds clozapine, an atypical neuroleptic useful for treatment-resistant schizophrenia. In addition, ADRA2C binds clonidine which is prescribed for three psychiatric diseases. This report communicates the findings of the genetic scanning of this gene of very tough GC content. The complete coding sequences and splice junctions were scanned with [DOVAM]-S in 104 schizophrenics, and pilot probes of patients with alcoholism (41 patients), cocaine abuse (25 patients), puerperal psychosis (30 patients), attention deficient/hyperactivity disorder (25 patients) and autism (25 patients). Six sequence variants were found, including five silent polymorphisms (allele frequencies 0.6--25%) and an in-frame deletion of a homologous repeat at nucleotides 967--978 (ie, TIDRU(1)). Genotyping of the normal two repeat unit of the Third Intracytoplasmic Domain Repeat Unit (TIDRU(2)) and the deleted variant (TIDRU(1)) revealed that TIDRU(1) had allelic frequencies of 39% (11/28) and 3.5% (6/172) in African-American and Caucasian schizophrenics, respectively, and it occurred with equal frequency in controls (44%, 31/70 and 3.0%, 6/198). TIDRU(1) occurs at a location similar to the third intracytoplasmic 48-nucleotide repeat unit in the DRD4 that is associated with ADHD. Although these data do not suggest an association of TIDRU(1) with schizophrenia, additional studies are needed to see whether TIDRU(1) confers a clinical phenotype.
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PMID:An in-frame deletion in the alpha(2C) adrenergic receptor is common in African--Americans. 1131 18

The title of this contribution involves two consecutive questions: have the effects of medication in autism indeed been disappointing? And if so, why? The answer to the first question depends on whether one focuses on the core social and communicative deficits of autism, or on various complicating behaviour problems. Attempts over the past decades to develop drugs that specifically improve social and communicative functioning have failed. Among the most ambitious attempts were medical interventions in the endogenous opioid system that were motivated from animal models on the involvement of this system in various aspects of social behaviour. By contrast, medications such as the newer antipsychotics, psychostimulants, presynaptic noradrenergic blocking agents (clonidine and guanfacine) and selective serotonin reuptake inhibitors were shown to reduce impairing complicating symptoms of affective instability, irritability, hyperactivity and inattentiveness, aggression, self-injury and stereotypies. The explanation for the medication-refractory status of social and communicative deficits should be sought in at least two related factors: (1) the as yet unidentified neurochemical basis of autism, and (2) the obvious lack of involvement of the main neurotransmitter systems (dopamine, noradrenaline and serotonin) in the pathophysiology of social and communicative behaviour.
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PMID:Why have drug treatments been so disappointing? 1452 Nov 96

The isoprenoid pathway and its metabolites--digoxin, dolichol, and ubiquinone--were assessed in autism. The isoprenoid pathway and digoxin status was also studied for comparison in individuals of differing hemispheric dominance to determine the role of cerebral dominance in the genesis of autism. There was an upregulation of the isoprenoid pathway as evidenced by elevated HMG CoA reductase activity in autism. Digoxin, an endogenous Na+-K+ ATPase inhibitor secreted by the hypothalamus, was found to be elevated and RBC membrane Na+-K+ ATPase activity was found to be reduced in autism. Membrane Na+-K+ ATPase inhibition can result in increased intracellular Ca2+ and reduced magnesium levels. Hypothalamic digoxin can modulate conscious and subliminal perception and its dysfunction may lead to autism. Digoxin can also preferentially upregulate tryptophan transport over tyrosine resulting in increased levels of depolarizing tryptophan catabolites--serotonin, quinolinic acid (NMDA agonist), strychnine (blocks glycinergic inhibitory transmission), and nicotine (promotes dopamine release) and decreased levels of hyperpolarizing tyrosine catabolites--dopamine, noradrenaline, and morphine--contributing to membrane Na+-K+ ATPase inhibition. Increased nicotine levels can produce increased dopaminergic transmission in the presence of low dopamine levels. NMDA excitotoxicity could result from hypomagnesemia induced by membrane Na+-K+ ATPase inhibition and quinolinic acid, an NMDA agonist acting on the NMDA receptor. Hypomagnesemia and increased dolichol level can affect glycoconjugate metabolism and membranogenesis leading on to disordered synaptic connectivity in the limbic allocortex and defective presentation of viral antigens and neuronal antigens contributing to autoimmunity and viral persistence important in the pathogenesis. Membrane Na+-K+ ATPase inhibition can produce immune activation, a component of autoimmunity. Mitochondrial dysfunction consequent to altered calcium/magnesium ratios and reduced ubiquinone levels can result in increased free radical generation and reduced free radical scavenging and defective apoptosis leading to abnormal synaptogenesis. Autism can thus be considered a syndrome of hypothalamic digoxin hypersecretion consequent to an upregulated isoprenoid pathway. The biochemical patterns including hyperdigoxinemia observed in autism correlated with those obtained in right hemispheric chemical dominance. Right hemispheric chemical dominance is a predisposing factor for autism.
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PMID:A hypothalamic digoxin-mediated model for autism. 1458 53

The dominant research subject on schizophrenia, mood disorders, autism and other central nervous system diseases has been related to neurotransmitter system abnormalities. For example, the dopamine hypothesis states that schizophrenia is the result of dopaminergic hyperactivity. The therapeutic approach has also been directed towards finding agents which will modulate or regulate these neurotransmitter systems at any step. There is substantial and mounting evidence that subtle abnormalities of reactive oxygen species (ROS) and nitric oxide (NO) may underlie a wide range of neuropsychiatric disorders. NO has chemical properties that make it uniquely suitable as an intracellular and intercellular messenger. It is produced by the activity of nitric oxide synthases which are present in peripheral tissues and in neurons. On the other hand, NO is known to be an oxygen radical in the central and peripheral nervous systems. NO has been implicated in a number of physiological functions such as noradrenaline and dopamine releases, memory and learning and certain pathologies such as schizophrenia, bipolar disorder and major depression. Evidence has been considered here for the proposal that an abnormality of NO metabolism may be a contributory factor in some neuropsychiatric disorders. The direct evidence for NO abnormalities in schizophrenia and other psychiatric disorders remains relatively limited to date, although there are some clinical and experimental studies. The suggestion that NO and other ROS may play a role in some neuropsychiatric disorders clearly has important implications for new treatment possibilities. The primary objective of the present review was to summarize and critically evaluate the current knowledge regarding a potential contribution of NO to the neuropathophysiology of schizophrenia as well as other neuropsychiatric disorders.
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PMID:Nitric oxide as a physiopathological factor in neuropsychiatric disorders. 1534 Nov 94

Previous studies suggest that dysfunction of neurotransmitter systems is associated with the pathology of autism in humans and the disease model rodents, but the precise mechanism is not known. Rodent offspring exposed prenatally to VPA shows autism-related behavioral abnormalities. The present study examined the effect of prenatal VPA exposure on brain monoamine neurotransmitter systems in male and female mice. The prenatal VPA exposure did not affect the levels of dopamine (DA), noradrenaline (NA), serotonin (5-HT) and their metabolites in the prefrontal cortex and striatum, while it significantly reduced methamphetamine (METH) (1.0 mg/kg)-induced hyperlocomotion in male offspring. In vivo microdialysis study demonstrated that prenatal VPA exposure attenuated METH-induced increases in extracellular DA levels in the prefrontal cortex, while it did not affect those in extracellular NA and 5-HT levels. Prenatal VPA exposure also decreased METH-induced c-Fos expression in the prefrontal cortex and the mRNA levels of DA D1 and D2 receptors in the prefrontal cortex. These effects of VPA were not observed in the striatum. In contrast to male offspring, prenatal VPA exposure did not affect METH-induced increases in locomotor activity and prefrontal DA levels and the D1 and D2 receptor mRNA levels in the prefrontal cortex in female offspring. These findings suggest that prenatal VPA exposure causes hypofunction of prefrontal DA system in a sex-dependent way.
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PMID:Reduced prefrontal dopaminergic activity in valproic acid-treated mouse autism model. 2590 43


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