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)

The deletion 22q13.3 syndrome (deletion 22q13 syndrome or Phelan-McDermid syndrome) is a chromosome microdeletion syndrome characterized by neonatal hypotonia, global developmental delay, normal to accelerated growth, absent to severely delayed speech, and minor dysmorphic features. The deletion occurs with equal frequency in males and females and has been reported in mosaic and non-mosaic forms. Due to lack of clinical recognition and often insufficient laboratory testing, the syndrome is under-diagnosed and its true incidence remains unknown. Common physical traits include long eye lashes, large or unusual ears, relatively large hands, dysplastic toenails, full brow, dolicocephaly, full cheeks, bulbous nose, and pointed chin. Behavior is autistic-like with decreased perception of pain and habitual chewing or mouthing. The loss of 22q13.3 can result from simple deletion, translocation, ring chromosome formation and less common structural changes affecting the long arm of chromosome 22, specifically the region containing the SHANK3 gene. The diagnosis of deletion 22q13 syndrome should be considered in all cases of hypotonia of unknown etiology and in individuals with absent speech. Although the deletion can sometimes be detected by high resolution chromosome analysis, fluorescence in situ hybridization (FISH) or array comparative genomic hybridization (CGH) is recommended for confirmation. Differential diagnosis includes syndromes associated with hypotonia, developmental delay, speech delay and/or autistic-like affect (Prader-Willi, Angelman, Williams, Smith-Magenis, Fragile X, Sotos, FG, trichorhinophalangeal and velocardiofacial syndromes, autism spectrum disorders, cerebral palsy). Genetic counseling is recommended and parental laboratory studies should be considered to identify cryptic rearrangements and detect parental mosaicism. Prenatal diagnosis should be offered for future pregnancies in those families with inherited rearrangements. Individuals with deletion 22q13 should have routine examinations by the primary care physician as well as genetic evaluations with referral to specialists if neurological, gastrointestinal, renal, or other systemic problems are suspected. Affected individuals benefit from early intervention programs, intense occupational and communication therapies, adaptive exercise and sport programs, and other therapies to strengthen their muscles and increase their communication skills. No apparent life-threatening organic abnormalities accompany the diagnosis of deletion 22q13.
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PMID:Deletion 22q13.3 syndrome. 1850 57

A 22-year-old male patient with autism and epilepsy was scheduled to undergo impacted third molar extractions at an outpatient setting. Oral preanesthetic medication with dexmedetomidine and subsequent midazolam with ketamine was acceptable and effective to place intravenous cannula. General anesthesia was maintained with intravenous propofol and dexmedetomidine and operation was performed uneventfully. Sedation with intravenous dexmedetomidine was continued after operation to attenuate and/or manage postoperative problems, such as emergence agitation, dysphoric reactions, pain, opioid-related nausea/vomiting and seizure. He recovered from postoperative sedation and was discharged home without significant problems. Oral and intravenous dexmedetomidine was useful for anesthetic care in the uncooperative patient.
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PMID:[Ambulatory anesthesia for an adult patient with autism and epilepsy: sedation using oral and intravenous dexmedetomidine]. 1854 4

Symptoms of bone pain and skin rashes are not uncommon following a variety of infectious illnesses, but the underlying mechanisms are not well understood. The case of a 9-year-old boy with autism was recently described, who was hospitalized because of pain in the right hip, refusal to walk, fatigue, irritability, skin rash, and subsequent gingival swelling after an unspecified upper respiratory illness. The boy was diagnosed with scurvy. However, the gingival symptoms occurred after treatment with indomethacin, which lowers vitamin C levels; severe bone pain and fatigue are also well-documented symptoms of hypervitaminosis A. This review of a case report of a boy with autism provides an opportunity to present a new hypothesis of the mechanism of these postinfection symptoms in the context of an increasingly common condition of childhood.
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PMID:Bone pain, growth failure, and skin rash after an upper respiratory illness in a boy with autism: possible association with altered retinoid metabolism. 1856 48

Autism is a developmental disorder characterized by severe deficits in social interaction and communication. A wide spectrum of medical and behavioral symptoms is exhibited by children with autism, which makes routine dental care very difficult in them. Bruxism or forceful grinding of teeth is one of the sleep problems commonly observed in children with autism. Our patient, a 4-year-old male child with autism, presented with complaints of pain and sensitivity of the teeth. There was history of excessive grinding and clenching of teeth. Limited oral examination revealed severe attrition of all primary teeth. Treatment was planned under general anesthesia because of his poor cognitive abilities. Full-mouth rehabilitation, including placement of stainless steel crowns for all primary molars, was done. Following treatment there was a significant decrease in the grinding habit over the next 2 months. Although the communication and behavioral problems in children with autism pose challenges for the dentist, treatment with proper planning and a lot of patience can definitely make a difference.
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PMID:Management of a child with autism and severe bruxism: a case report. 1860 35

Autism and schizophrenia are multifactorial disorders with increasing prevalence in the young population. Among candidate molecules, reelin (RELN) is a protein of the extracellular matrix playing a key role in brain development and synaptic plasticity. The heterozygous (HZ) reeler mouse provides a model for studying the role of reelin deficiency for the onset of these syndromes. We investigated whether early indices of neurobehavioral disorders can be identified in the infant reeler, and whether the consequences of ontogenetic adverse experiences may question or support the suitability of this model. A first study focused on the link between early exposure to Chlorpyryfos and its enduring neurobehavioral consequences. Our data are interesting in view of recently discovered cholinergic abnormalities in autism and schizophrenia, and may suggest new avenues for early pharmacological intervention. In a second study, we analyzed the consequences of repeated maternal separation early in ontogeny. The results provide evidence of how unusual stress early in development are converted into altered behavior in some, but not all, individuals depending on gender and genetic background. A third study aimed to verify the reliability of the model at critical age windows. Data suggest reduced anxiety, increased impulsivity and disinhibition, and altered pain threshold in response to morphine for HZ, supporting a differential organization of brain dopaminergic, serotonergic and opioid systems in this genotype. In conclusion, HZ exhibited a complex behavioral and psycho-pharmacological phenotype, and differential responsivity to ontogenetic adverse conditions. HZ may be used to disentangle interactions between genetic vulnerability and environmental factors. Such an approach could help to model the pathogenesis of neurodevelopmental psychiatric diseases.
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PMID:Gene-environment interaction during early development in the heterozygous reeler mouse: clues for modelling of major neurobehavioral syndromes. 1884 82

The spectrum of neurological conditions and psychiatric disorders affected by valproic acid (VPA) ranges from control of seizure and mood disorders to migraine, neuropathic pain, and even congenital malformations and autism. While widely used clinically, the mechanism(s) of action of VPA is not completely understood. Emerging evidence indicates that brain noradrenergic systems contribute to the symptoms of mood disorders and may involve regulation of tyrosine hydroxylase (TH) expression, the rate-limiting enzyme in the biosynthesis of dopamine, norepinephrine and epinephrine. We previously showed that the structurally related short chain fatty acid sodium butyrate (SB) induces TH transcription and alters TH mRNA stability in PC12 cells. The present study was undertaken to determine whether the branched short chain fatty acid VPA could also regulate TH gene expression in vitro. Similar to SB, VPA induced TH transcription at all concentrations tested. VPA-stimulated transcription was significantly attenuated by introducing point mutations in either the canonical cAMP- or in the butyrate-response elements of the TH promoter; or by co-expression of dominant-negative forms of CREB. As with SB, increasing concentrations of VPA demonstrated opposing effects on TH mRNA and protein abundance: elevation of both at low (0.1 mM) but attenuation at concentrations higher than 0.5 mM. This concentration-dependence is consistent with a novel and previously unrecognized cellular/molecular drug regulatory step at the level of TH mRNA stability. Thus, the therapeutic efficacy of VPA might be related to its ability to regulate TH mRNA and protein levels, and thereby central catecholaminergic-dependent behavioral pathways.
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PMID:Valproic acid regulates catecholaminergic pathways by concentration-dependent threshold effects on TH mRNA synthesis and degradation. 1897 38

Neuroligins (NL) are postsynaptic cell adhesion molecules that are thought to specify synapse properties. Previous studies showed that mutant mice carrying an autism-associated point mutation in NL3 exhibit social interaction deficits, enhanced inhibitory synaptic function and increased staining of inhibitory synaptic puncta without changes in overall inhibitory synapse numbers. In contrast, mutant mice lacking NL2 displayed decreased inhibitory synaptic function. These studies raised two relevant questions. First, does NL2 deletion impair inhibitory synaptic function by altering the number of inhibitory synapses, or by changing their efficacy? Second, does this effect of NL2 deletion on inhibition produce behavioral changes? We now show that although NL2-deficient mice exhibit an apparent decrease in number of inhibitory synaptic puncta, the number of symmetric synapses as determined by electron microscopy is unaltered, suggesting that NL2 deletion impairs the function of inhibitory synapses without decreasing their numbers. This decrease in inhibitory synaptic function in NL2-deficient mice correlates with a discrete behavioral phenotype that includes a marked increase in anxiety-like behavior, a decrease in pain sensitivity and a slight decrease in motor co-ordination. This work confirms that NL2 modulates inhibitory synaptic function and is the first demonstration that global deletion of NL2 can lead to a selective behavioral phenotype.
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PMID:Increased anxiety-like behavior in mice lacking the inhibitory synapse cell adhesion molecule neuroligin 2. 1901 88

The effectiveness and safety of a group aquatic aerobic exercise program on cardiorespiratory endurance for children with disabilities was examined using an A-B study design. Sixteen children (11 males, five females) age range 6 to 11 years (mean age 9y 7mo [SD 1y 4mo]) participated in this twice-per-week program lasting 14 weeks. The children's diagnoses included autism spectrum disorder, myelomeningocele, cerebral palsy, or other developmental disability. More than half of the children ambulated independently without aids. Children swam laps and participated in relay races and games with a focus of maintaining a defined target heart rate zone. The strengthening component consisted of exercises using bar bells, aquatic noodles, and water resistance. The following outcomes were measured: half-mile walk/run, isometric muscle strength, timed floor to stand 3-meter test, and motor skills. Complaints of pain or injury were systematically collected. Significant improvements in the half-mile walk/run were observed, but not for secondary outcomes of strength or motor skills. The mean program attendance was 80%, and no injury was reported. Children with disabilities may improve their cardiorespiratory endurance after a group aquatic aerobic exercise program with a high adult:child ratio and specific goals to maintain training heart rates.
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PMID:Group aquatic aerobic exercise for children with disabilities. 1904 77

Nicotine addiction begins with high-affinity binding of nicotine to acetylcholine (ACh) receptors in the brain. The end result is over 4,000,000 smoking-related deaths annually worldwide and the largest source of preventable mortality in developed countries. Stress reduction, pleasure, improved cognition and other central nervous system effects are strongly associated with smoking. However, if nicotine activated ACh receptors found in muscle as potently as it does brain ACh receptors, smoking would cause intolerable and perhaps fatal muscle contractions. Despite extensive pharmacological, functional and structural studies of ACh receptors, the basis for the differential action of nicotine on brain compared with muscle ACh receptors has not been determined. Here we show that at the alpha4beta2 brain receptors thought to underlie nicotine addiction, the high affinity for nicotine is the result of a strong cation-pi interaction to a specific aromatic amino acid of the receptor, TrpB. In contrast, the low affinity for nicotine at the muscle-type ACh receptor is largely due to the fact that this key interaction is absent, even though the immediate binding site residues, including the key amino acid TrpB, are identical in the brain and muscle receptors. At the same time a hydrogen bond from nicotine to the backbone carbonyl of TrpB is enhanced in the neuronal receptor relative to the muscle type. A point mutation near TrpB that differentiates alpha4beta2 and muscle-type receptors seems to influence the shape of the binding site, allowing nicotine to interact more strongly with TrpB in the neuronal receptor. ACh receptors are established therapeutic targets for Alzheimer's disease, schizophrenia, Parkinson's disease, smoking cessation, pain, attention-deficit hyperactivity disorder, epilepsy, autism and depression. Along with solving a chemical mystery in nicotine addiction, our results provide guidance for efforts to develop drugs that target specific types of nicotinic receptors.
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PMID:Nicotine binding to brain receptors requires a strong cation-pi interaction. 1925 81

Oxytocin (Oxt) is a nonapeptide hormone best known for its role in lactation and parturition. Since 1906 when its uterine-contracting properties were described until 50 years later when its sequence was elucidated, research has focused on its peripheral roles in reproduction. Only over the past several decades have researchers focused on what functions Oxt might have in the brain, the subject of this review. Immunohistochemical studies revealed that magnocellular neurons of the hypothalamic paraventricular and supraoptic nuclei are the neurons of origin for the Oxt released from the posterior pituitary. Smaller cells in various parts of the brain, as well as release from magnocellular dendrites, provide the Oxt responsible for modulating various behaviors at its only identified receptor. Although Oxt is implicated in a variety of "non-social" behaviors, such as learning, anxiety, feeding and pain perception, it is Oxt's roles in various social behaviors that have come to the fore recently. Oxt is important for social memory and attachment, sexual and maternal behavior, and aggression. Recent work implicates Oxt in human bonding and trust as well. Human disorders characterized by aberrant social interactions, such as autism and schizophrenia, may also involve Oxt expression. Many, if not most, of Oxt's functions, from social interactions (affiliation, aggression) and sexual behavior to eventual parturition, lactation and maternal behavior, may be viewed as specifically facilitating species propagation.
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PMID:Oxytocin: the great facilitator of life. 1948 29


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