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

Autism is a neurodevelopmental disorder that according to the Centers for Disease Control and Prevention (CDC) affects 1 in 150 children in the United States. Autism is characterized by impairments in social relatedness and communication, repetitive behaviors, abnormal movements, and sensory dysfunction. Recently emerging evidence suggests that mercury, especially from childhood vaccines, appears to be a factor in the development of the autistic disorders, and that autistic children have higher than normal body-burdens of mercury. In considering mercury toxicity, it has previously been shown that testosterone significantly potentates mercury toxicity, whereas estrogen is protective. Examination of autistic children has shown that the severity of autistic disorders correlates with the amount of testosterone present in the amniotic fluid, and an examination of a case-series of autistic children has shown that some have plasma testosterone levels that were significantly elevated in comparison neurotypical control children. A review of some of the current biomedical therapies for autistics, such as glutathione and cysteine, chelation, secretin, and growth hormone, suggests that they may in fact lower testosterone levels. We put forward the medical hypothesis that autistic disorders, in fact, represents a form of testosterone mercury toxicity, and based upon this observation, one can design novel treatments for autistics directed towards higher testosterone levels in autistic children. We suggest a series of experiments that need to be conducted in order to evaluate the exact mechanisms for mercury-testosterone toxicity, and various types of clinical manipulations that may be employed to control testosterone levels. It is hoped by devising therapies that address the steroid hormone pathways, in addition to the current treatments that successful lower heavy metal body-burdens of mercury, will work synergistically to improve clinical outcomes. In light of the fact that there are a number of other diseases that may have a chronic mercury toxicity component, such as Alzheimer's disease, heart disease, obesity, ALS, asthma, and other various forms of autoimmune disorders, it is imperative that further research should be conducted to understand mercury-testosterone toxicity.
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PMID:The potential importance of steroids in the treatment of autistic spectrum disorders and other disorders involving mercury toxicity. 1578 Apr 90

Stereotypical movements are characteristic of autism or mental retardation but can also occur in patients with dementia, particularly frontotemporal dementia (FTD). In this study, we administered the Abnormal Involuntary Movement Scale (AIMS) to 18 patients with FTD and to 18 patients with the most common form of dementia, Alzheimer's disease (AD). The AIMS scores were gathered at the initial presentation of patients who had not received antipsychotic medications. Compared to the AD patients, the FTD patients had significantly more stereotypical movements, including frequent rubbing behaviors and some self-injurious acts. All the FTD patients with stereotypical movements had compulsive-like behaviors, suggesting a similar pathophysiologic cause, and most had a decrease in their stereotypical movements with the administration of sertraline, a serotonin selective reuptake inhibitor.
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PMID:Stereotypical movements and frontotemporal dementia. 1578 92

Amalgam, which has been in use in dentistry for 150 years, consists of 50 % elemental mercury and a mixture of silver, tin, copper and zinc. Minute amounts of mercury vapour are released continuously from amalgam. Amalgam contributes substantially to human mercury load. Mercury accumulates in some organs, particularly in the brain, where it can bind to protein more tightly than other heavy metals (e. g. lead, cadmium). Therefore, the elimination half time is assumed to be up to 1 - 18 years in the brain and bones. Mercury is assumed to be one of the most toxic non-radioactive elements. There are pointers to show that mercury vapour is more neurotoxic than methyl-mercury in fish. Review of recent literature suggests that mercury from dental amalgam may lead to nephrotoxicity, neurobehavioural changes, autoimmunity, oxidative stress, autism, skin and mucosa alterations or non-specific symptoms and complaints. The development of Alzheimer's disease or multiple sclerosis has also been linked to low-dose mercury exposure. There may be individual genetical or acquired susceptibilities for negative effects from dental amalgam. Mercury levels in the blood, urine or other biomarkers do not reflect the mercury load in critical organs. Some studies regarding dental amalgam reveal substantial methodical flaws. Removal of dental amalgam leads to permanent improvement of various chronic complaints in a relevant number of patients in various trials. Summing up, available data suggests that dental amalgam is an unsuitable material for medical, occupational and ecological reasons.
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PMID:[Amalgam risk assessment with coverage of references up to 2005]. 1670 56

Imprinted genes are epigenetically modified genes whose expression is determined according to their parent of origin. They are involved in embryonic development, and imprinting dysregulation is linked to cancer, obesity, diabetes, and behavioral disorders such as autism and bipolar disease. Herein, we train a statistical model based on DNA sequence characteristics that not only identifies potentially imprinted genes, but also predicts the parental allele from which they are expressed. Of 23,788 annotated autosomal mouse genes, our model identifies 600 (2.5%) to be potentially imprinted, 64% of which are predicted to exhibit maternal expression. These predictions allowed for the identification of putative candidate genes for complex conditions where parent-of-origin effects are involved, including Alzheimer disease, autism, bipolar disorder, diabetes, male sexual orientation, obesity, and schizophrenia. We observe that the number, type, and relative orientation of repeated elements flanking a gene are particularly important in predicting whether a gene is imprinted.
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PMID:Genome-wide prediction of imprinted murine genes. 1593 Apr 97

Brain-derived neurotrophic factor (BDNF) is a member of a family of neurotrophins that, by activating a tyrosine kinase B receptor (TrkB), regulates a wide variety of processes in the nervous system, including neural development, function and survival. Evidence suggests that excess BDNF is involved in the pathogenesis of epilepsy, mania and autism. Thus, agents that can decrease BDNF-TrkB pathway signaling may be therapeutic for these diseases. However, blocking BDNF-TrkB pathways with TrkB antagonists may be harmful, as BDNF-TrkB deficiency has been related to major depression and Alzheimer's disease. A partial agonist is an agent that elicits a maximum response that is less than that of an agonist (e.g., the physiological ligand), so, in the presence of excess full agonist, a partial agonist would act as an antagonist. Interestingly, a dopaminergic partial agonist, aripiprazole, has been successfully developed for the treatment of psychotic disorders. Recently specific TrkB partial agonists have been synthesized by O'Leary and Hughes; it is proposed that these partial TrkB agonists may provide a novel strategy for the treatment of epilepsy, mania or autism, which may be associated with BDNF-TrkB hyperfunction.
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PMID:TrkB partial agonists: potential treatment strategy for epilepsy, mania, and autism. 1602 1

Historically, immunological research in psychiatry was based on empirical findings and early epidemiological studies indicating a possible relationship between psychiatric symptoms and acute infectious diseases. However, aetiopathological explanations for psychiatric disorders are no longer closely related to acute infection. Nevertheless, immune hypotheses have been discussed in schizophrenia, affective disorders and infantile autism in the last decades. Although the variability between the results of the epidemiological studies conducted to date is strikingly high, there is still some evidence that the immune system might play a role in the aetiopathogenesis of these three psychiatric diseases, at least in subgroups of patients. In anxiety disorders immunological research is still very much in its infancy, and the few and inconsistent data of immune changes in these patients are believed to reflect the influence of short- or long-term stress exposure. Nevertheless, there are also some hints raising the possibility that autoimmune mechanisms could interrupt neurotransmission, which would be of significance in certain patients with anxiety and panic disorders. Drug and alcohol (ethanol) dependence are not believed to be primarily influenced by an immunological aetiology. On the other hand, immune reactions due to different drugs of abuse and alcohol may directly or indirectly influence the course of concomitant somatic diseases. In different organic brain disorders the underlying somatic disease is defined as a primary immune or autoimmune disorder, for instance HIV infection or systemic lupus erythematosus (SLE). For other neurodegenerative disorders, such as Alzheimer's disease, immunoaetiopathological mechanisms are supported by experimental and clinical studies. Treatment strategies based on immune mechanisms have been investigated in patients with schizophrenia and affective disorders. Furthermore, some antipsychotics and most antidepressants are known to have direct or indirect effects on the immune system. Different immunotherapies have been used in autism, including transfer factor, pentoxifylline, intravenous immunoglobulins and corticosteroids. Immunosuppressive and/or immunomodulating agents are well established methods for treating the neuropsychiatric sequelae of immune or autoimmune disorders, for example AIDS and SLE. Therapeutic approaches in Alzheimer's disease also apply immunological methods such as strategies of active/passive immunisation and NSAIDs. Considering the comprehensive interactive network between mind and body, future research should focus on approaches linking targets of the different involved systems.
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PMID:Immunological aetiology of major psychiatric disorders: evidence and therapeutic implications. 1603 89

The well-known family of low-density lipoprotein receptors represents a collection of ancient membrane receptors that have been remarkably conserved throughout evolution. These multifunctional receptors, known to regulate cholesterol transport, are becoming increasingly interesting to the neuroscience community due to their ability to transduce a diversity of extracellular signals across the membrane in the adult CNS. Their roles in modulating synaptic plasticity and necessity in hippocampus-specific learning and memory have recently come to light. In addition, genetic, biochemical and behavioral studies have implicated these signaling systems in a number of human neurodegenerative and neuropsychiatric disorders involving loss of cognitive ability, such as Alzheimer's disease, schizophrenia and autism. This review describes the known functions of these receptors and discusses their potential role in processes of synaptic regulation and memory formation.
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PMID:A fresh look at an ancient receptor family: emerging roles for low density lipoprotein receptors in synaptic plasticity and memory formation. 1619 8

Membrane and vesicular monoaminergic transporters, responsible for the homeostasis of neurotransmitter pools at nerve endings, are very involved in the physiology and diseases of central nervous system. Recent progresses of cerebral molecular imaging using SPECT and PET methods allow the extend of in vivo exploration of these transporters. For this aim, an increasing number of radiopharmaceuticals labelled with [123I], [99mTc], [11C] or [18F] have been developed such as cocaine derivatives for the DAT, compounds from the diphenyl sulfide family for the SERT, and dihydrotetrabenazine derivatives for the VMAT2. These functional imaging methods can be very useful in several neurological and psychiatric disorders which involve the monoaminergic neurotransmission systems such as Parkinson's disease, ADHD, depression and autism. For example, the DAT is a specific index of the density of dopaminergic endings which progressively degenerate in Parkinson's disease. In vivo exploration of this transporter can therefore be a relevant way (i) to realize an early detection of the loss of dopaminergic neurons, (ii) to assess the progression of the disease, (iii) to validate and improve the efficacy of new therapeutic strategies such as neuroprotection and neuroreparation. In all, the extend of in vivo exploration of monoamine transporters will allow great progress for (1) knowledge of physiopathological mechanisms of brain disorders, (2) early diagnosis of cerebral dysfunctions, allowing early use of new therapies, (3) selection of homogenous classes of subjects for therapeutic assays, (4) objectiveness of drug-molecular target interaction, (5) follow-up of disease evolution and treatment.
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PMID:PET and SPECT exploration of central monoaminergic transporters for the development of new drugs and treatments in brain disorders. 1625 Aug 52

Evidence supports the hypothesis that normalization of cholinergic tone by selective antagonism of neuronal nicotinic acetylcholine receptors (NNRs) may ameliorate the core symptoms of autism. As often is the case, epidemiology has provided the first important clues. It is well recognized that psychiatric patients are significantly more often smokers than the general population. The only known exceptions are obsessive-compulsive disorder (OCD), catatonic schizophrenia and interestingly, autism. In this regard, clinical studies with nicotine have demonstrated amelioration of symptoms of a number of diseases and disorders, including Alzheimer's disease, Parkinson's disease, ADHD and Tourette's syndrome. Nicotine's agonist properties at CNS NNRs have been implicated in these effects and support the concept of self-medication as a strong motivation for smoking in cognitively compromised individuals. On the other hand, the inverse correlation between autism and smoking suggests that smoking does not provide symptomatic relief and may actually be indicative of an active avoidance of nicotine's agonist effects in this disorder. Neuroanatomical evidence is consistent with this idea based on the presence of hypercholinergic architecture in the autistic brain, particularly during the first few years of development, making the avoidance of further stimulation of an already hyperactive cholinergic system plausible. This may also explain why stimulants (known to increase dopamine levels as do NNR agonists) appear to aggravate autistic symptoms and why studies with cholinesterase inhibitors that increase acetylcholine levels in the brain have yielded variable effects in autism. Taken together, the evidence suggests the possibility that nicotinic cholinergic antagonism may in fact be palliative. Pharmacological evidence supports this hypothesis. For example, antidepressants, many of which are now known to be non-competitive NNR antagonists, have been used successfully to treat a number of autistic symptoms. More specifically, there is anecdotal evidence from at least one medical practitioner that mecamylamine, a non-selective NNR antagonist, is effective in treating many autistic symptoms, particularly those that are refractory to most other treatments. Clearly there is a need for carefully controlled clinical studies with novel selective NNR antagonists to explore their potential as a new and exciting approach for the treatment of autism.
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PMID:Nicotinic cholinergic antagonists: a novel approach for the treatment of autism. 1640 87

The mammalian bombesin (BB)-like peptide gastrin-releasing peptide (GRP) stimulates cell proliferation, displays a range of neuroendocrine activities, and acts as a growth factor in the pathogenesis of several types of human cancer. Several lines of evidence have indicated that GRP and its receptor (GRPR) might also be involved in the neurochemical alterations associated with psychiatric and neurological disorders. GRP and GRPR are distributed throughout the mammalian central nervous system (CNS). Altered levels of BB-like peptides have been found in the CNS of patients with schizophrenia and Parkinson's disease. Dysfunctions in GRPR-induced cellular calcium signaling have been reported in fibroblasts from patients with Alzheimer's disease. A translocation in the GRPR gene has been associated with autism. Pharmacological and genetic studies in rodents have shown that GRPRs in brain areas such as the dorsal hippocampus and amygdala are importantly involved in regulating synaptic plasticity and aspects of behavior that might be altered in disorders such as anxiety, schizophrenia, depression, autism and dementia. Behaviors modulated by the GRPR in rodents include grooming, food intake, stereotypy, social behavior, and emotionally-motivated learning and memory. Together, these findings support the view that the GRPR should be considered a therapeutic target for a subset of CNS diseases.
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PMID:Gastrin-releasing peptide receptor as a molecular target for psychiatric and neurological disorders. 1661 Oct 92


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