Lec11-Retardation - Neurobiology of Learning and Memory...

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Unformatted text preview: Neurobiology of Learning and Memory Prof. Anagnostaras Lec 10: Mental Retardation Mental What is retardation? DSM Criteria q q q IQ of 70 or below (Normal mean = 100, SD = 15, so 2 SD) Deficits or impairments in present adaptive functioning in at least two Deficits of the following: of Communication Self Care Home Living Social/ Interpersonal Skills Community Resources Self-Direction Functional Academic Skills Work, Leisure, Health, and Safety Functional Onset before the age of 18 **arrested development** Onset **arrested Differential Diagnosis: q q q Learning Disorders or Communication Disorders Dementia Pervasive developmental disorders Etiology of Mental Retardation At least 1.5 million in the US have MR q Genetics q SES q Cultural deprivation q Diet q Drugs (Alcohol) q Parity q Mother’s Age q Prenatal factors MR and Mother’s Age 16-20 = 1 in 2,000 21-25 = 1 in 1,500 26-30 = 1 in 1,000 31-35 = 1 in 750 36-44 = 1 in 37 45-up = 1 in 12 • Just because it isn’t heritable doesn’t mean it isn’t genetic! mean Severity of Retardation Mild Retardation: 85% of MR, IQ 50-55 to 70 IQ develop social and communication skills in preschool years develop often not distinguishable from children without retardation until later age age only acquire academic skills up to approximately 6th grade level only as adults- maintain unskilled jobs may need social and financial assistance assistance Moderate Retardation: 10% of MR, IQ 35-40 to 50-55 IQ acquire communication skills in later childhood years unlikely to progress beyond 2nd grade level unlikely difficulties recognizing social conventions and may interfere with pure relationships pure needs to be supervised needs Severity of Retardation Severe Retardation: 3-4% of MR, IQ 20-25 to 35-40 little or no communicative speech function on an elementary level in both speech and self care physical abnormalities need constant supervision Profound Retardation: 1-2% of MR, IQ below 20-25 neurological condition accounts for MR motor development, self care and communication skills may improve if appropriate instruction is provided but most can only perform simple tasks when heavily supervised Causes Hundreds of causes identified, although onethird of cases unknown • Most involve a disruption of gene, or gene expression (i.e, “genomic”), but may or may not be heritable or familial Most common: Fetal Alcohol Syndrome Down’s Syndrome (Trisomy 21) Fragile X Syndrome Low Heritability of Severe Retardation Genetic forms: chromosomal abnormalities Severe Chromosomal Abnormalities mostly spontaneous DS WS XXX XXY AS Mild PWS XYY XO Down’s Syndrome (1 in 1,000) Trisomy 21 Most develop Alzheimer’s & lethal William’s Syndrome (1 in 25,000) - Chr 7 LimK Triple X Syndrome (1 in 1,000 F) XXY Male Syndrome (1 in 750 M) Angelman Syndrome (1 in 25,000) from mother 15q11, UBE3A, GABR3 affected Prader-Willi Syndrome (1 in 15,000) from father same locus as AS, but SNRPN gene affected XYY Syndrome (1 in 1,000 M) Turner’s syndrome (1 in 2,500 F) Genetic forms: single-gene mutations Mild Severe Single gene mutations PKU Phenylketonuria (1 in 10,000) many mutations in PAH gene for phenylalanine hydoxylase *diet* RS Rett Syndrome (1 in 10,000 F, lethal in M) MECP2, methyl-CpG-binding protein-2 FRX Fragile X Syndrome (1 in 1,250 M, 1 in 2500 F) FMR1 expanding triplet repeat LNS Lesch-Nyhan Syndrome (1 in 20,000 M) HPRT1, hypoxanthine phosphoribosyltransferase DMD Duchenne Muscular Dystrophy (1 in 3,500 M) huge DMD gene produces dystrophin doesn’t affect mice NF1 Neurofibromatosis (1 in 3,000 births) huge NF1 gene Mean = 100 sd = 15 Many studies of genetic origins of low IQ, but not high IQ Proportion of scores Distribution of IQ 68.26% 95.44% 0.13% IQ score 0.13% 2.14% 13.59% 34.13% 34.13%13.59% 2.14% 50 PKU RS DS WS 70 FRX LNS 85 100 DMD XYY NF1 XO XXX, XXY AS, PWS 115 130 145 +4 IGF2 promotor PM >200 >150 Genius "Super Genius" Conclusions Multiple causes of retardation suggest that intelligence is complex >> easy to disrupt genetically or during development With few exceptions most forms of mental retardation involve disruption of genes, but may not be familial or heritable because mutation arises spontaneously Present studies focus on copying mutations in mice and then trying to treat deficits in mice. ...
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