Neurobiology of Learning and Memory Prof Anagnostaras Lec

Neurobiology of Learning and Memory Prof. Anagnostaras Lec 10: Mental Retardation

What is retardation? DSM Criteria IQ of 70 or below (Normal mean = 100, SD = 15, so 2 SD) Deficits or impairments in present adaptive functioning in at least two of the following: Communication Self Care Home Living Social/ Interpersonal Skills Community Resources Self-Direction Functional Academic Skills Work, Leisure, Health, and Safety Onset before the age of 18 **arrested development** Differential Diagnosis: Learning Disorders or Communication Disorders Dementia Pervasive developmental disorders

Etiology of Mental Retardation At least 1. 5 million in the US have MR Genetics SES Cultural deprivation Diet Drugs (Alcohol) Parity Mother’s Age 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!

Severity of Retardation Mild Retardation: 85% of MR, IQ 50 -55 to 70 develop social and communication skills in preschool years often not distinguishable from children without retardation until later age only acquire academic skills up to approximately 6 th grade level as adults- maintain unskilled jobs may need social and financial assistance Moderate Retardation: 10% of MR, IQ 35 -40 to 50 -55 acquire communication skills in later childhood years unlikely to progress beyond 2 nd grade level difficulties recognizing social conventions and may interfere with pure relationships needs to be supervised

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 Mild Severe Chromosomal Abnormalities mostly spontaneous DS Down’s Syndrome (1 in 1, 000) Trisomy 21 Most develop Alzheimer’s & lethal WS William’s Syndrome (1 in 25, 000) - Chr 7 Lim. K XXX Triple X Syndrome (1 in 1, 000 F) XXY Male Syndrome (1 in 750 M) AS Angelman Syndrome (1 in 25, 000) from mother 15 q 11, UBE 3 A, GABR 3 affected PWS Prader-Willi Syndrome (1 in 15, 000) from father same locus as AS, but SNRPN gene affected XYY Syndrome (1 in 1, 000 M) XO 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) MECP 2, methyl-Cp. G-binding protein-2 FRX Fragile X Syndrome (1 in 1, 250 M, 1 in 2500 F) FMR 1 expanding triplet repeat LNS Lesch-Nyhan Syndrome (1 in 20, 000 M) HPRT 1, hypoxanthine phosphoribosyltransferase DMD Duchenne Muscular Dystrophy (1 in 3, 500 M) huge DMD gene produces dystrophin doesn’t affect mice NF 1 Neurofibromatosis (1 in 3, 000 births) huge NF 1 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%13. 59% 2. 14% 50 PKU RS DS WS 70 FRX LNS 85 100 DMD XYY NF 1 XO XXX, XXY AS, PWS 115 130 145 +4 IGF 2 promotor PM >200 >150 "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.