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)

Autism is a highly disabling neurodevelopmental disorder characterized by social deficits, language impairment, and repetitive behaviors. There are few effective biological treatments for this disorder, partly due to the lack of translational biomarkers. However, recent data suggest that autism has reliable electrophysiological endophenotypes, along with evidence that some deficits may be caused by NMDA receptor (NMDAR) dysfunction. Similarly, the NMDAR antagonist MK801 has been used in behavioral animal models of autism. Since MK801 has also been used as a model of schizophrenia, this paper examines the independent and overlapping ways in which MK801 recreates the electrophysiogical changes present in both diseases. Mouse EEG was recorded in response to auditory stimuli after either vehicle or MK801 and the dose-response relationship for each measure was determined. ERP component amplitude and latency analysis was performed along with time-frequency analysis of gamma frequency inter-trial coherence and evoked power. Evoked gamma power and ITC were decreased by MK801 at the highest dose. P1, N1 latency and gamma baseline power were increased in dose dependent fashion following MK801. There were no amplitude changes in P1 or N1. MK801 caused alterations in evoked gamma activity, gamma ITC, gamma baseline power, P1 and N1 latency similar to findings in autism. These data provide evidence indicating that NMDAR dysfunction may contribute to deficits specific to autism and some that overlap with other disorders such as schizophrenia. Such observations could be important for developing novel therapeutics, as electrophysiological endophenotypes associate with functional measures and may provide early biomarkers for efficacy in clinical trials.
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PMID:NMDA antagonist MK801 recreates auditory electrophysiology disruption present in autism and other neurodevelopmental disorders. 2277 12

22q11 deletion syndrome (22qDS), also known as DiGeorge syndrome, is a copy number variant disorder that has a diverse clinical presentation including hypocalcaemia, learning disabilities, and psychiatric disorders. Many patients with 22q11DS present with signs that overlap with autism spectrum disorder (ASD) yet the possible physiological mechanisms that link 22q11DS with ASD are unknown. We hypothesized that early childhood hypocalcemia influences the neurobehavioral phenotype of 22q11DS. Drawing on a longitudinal cohort of 22q11DS patients, we abstracted albumin-adjusted serum calcium levels from 151 participants ranging in age from newborn to 19.5 years (mean 2.5 years). We then examined a subset of 20 infants and toddlers from this group for the association between the lowest calcium level on record and scores on the Communication and Symbolic Behavior Scales-Developmental Profile Infant-Toddler Checklist (CSBS-DP ITC). The mean (SD) age at calcium testing was 6.2 (8.5) months, whereas the mean (SD) age at the CSBS-DP ITC assessment was 14.7 (3.8) months. Lower calcium was associated with significantly greater impairment in the CSBS-DP ITC Social (p < 0.05), Speech (p < 0.01), and Symbolic domains (p < 0.05), in regression models adjusted for sex, age at blood draw, and age at the psychological assessment. Nevertheless, these findings are limited by the small sample size of children with combined data on calcium and CSBS-DP ITC, and hence will require replication in a larger cohort with longitudinal assessments. Considering the role of calcium regulation in neurodevelopment and neuroplasticity, low calcium during early brain development could be a risk factor for adverse neurobehavioral outcomes.
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PMID:The effect of hypocalcemia in early childhood on autism-related social and communication skills in patients with 22q11 deletion syndrome. 2526 2