Autism Flashcards
ASD diagnosis criteria for persistent deficits in social communication and interaction manifested as ____
. Deficits in social-emotional reciprocity
. Deficits in nonverbal communicative behaviors used for social interaction
. Deficits in developing, maintaining, and understanding relationships
ASD diagnosis criteria for restricted, repetitive patterns of behavior, interests, or activities as manifested by _____
. Stereotyped/repetitive motor movements, use of objects, or speech
. Insistence on sameness, inflexible adherence to routines, or ritualized patterns or verbal/nonverbal behavior
. Highly restricted, fixated interests that are abnormal in intensity or focus
. Hyper or hyporeactivity to sensory input or unusual interest in sensory aspects of environment
Incidence of ASD
. Males 4.5x more likely
. More than 80% of kids diagnosed under DSM 4 also fit criteria for DSM 5
Characteristic neurological abnormalities
. Alteration in size and time course of development of particular brain regions
. Cerebral cortex med. temporal lobe structures (amygdala and hippocampus) and corpus callosum are abnormal
. Time course issues can mess up brain connectivity patterns
Long-term consequences and comorbidities of ASD
. Not progressive
. Preference for routine and restricted behavior remains but object of obsession may change
. Hypersensitivity observed
. Seizure disorders common
. Allergies, asthma, digestive disorders, feeding and sleeping disorders observed
. Life expectancy not affected
. Mortality risk of autistic individuals is 2x as high as general population mostly due to accidents
Genetic factors of ASD
. Concordance of monozygotic twins is 60-90% of cases
. Concordance of dizygotic twins is 10-30%
. Have mutations in multiple genes leading to complex pattern of inheritance
. Alleles responsible for ASD are not the same in all individuals
. May have copy number variation
Environmental causes of ASD
. Most common: advanced parental age and extreme prematurity w/ very low birth weight
. Others: maternal DM, infection during pregnancy, complications at birth leading to O2 deprivation, exposure to pharmaceutical agents in womb , and exposure to other chemical agents
Syndromes presenting w/ ASD or ASD-like characteristics
. Rett syndrome: mutations in MECP2 (females only, 1/12,500-1/15,000)
. Angelman syndrome: imbalanced imprinting (1/10,000-1/20,000)
. Beckwith-Wiedemann syndrome: Imbalanced imprinting (1/13,000)
Contribution of imprinted genes on normal development
. Genes found in clusters as imprinted domains
. Play roles in control of embryonic growth and development
. Other imprinted genes function during postnatal development
Uniparental disomy
. Occurs when both copies of chromosomal pair originate from single parent
. If chromosome involved carried imprinted genes, this results in aberrant expression of these genes (overexpressed or silenced)
Chromosomal region 7q
. Linked to ASD through association studies
. Contains a few imprinted gene clusters
Genes involved in epigenetic regulation
. Epigenetic effectors/regulators: proteins involved in establishing, maintaining, or reading epigenetic marks
. Folate metabolism genes: required for production of donor methyl groups used in methylation reactions, disturbances can lead to methylation abnormalities disrupting expression of epigenetically regulated genes
Valproate
. Prenatal exposure to this is ASD risk factor
. Broad-spectrum anti-convulsants drug used to treat partial and generalized seizures
. Also used to treat migraines and bipolar
. Risk of getting ASD is 10%, higher when paired with other antiepileptic drugs
. Interferes w/ folate metabolism, oxidative stress, cell toxicity from metabolites, and inhibition of histone deacetylases (HDACs)
. Altered folate metabolism and HDAC inhibition are epigenetic in nature
