Neurobiology of Learning and Memory Prof. Anagnostaras Lec 10:

Mental Retardation

What is retardation?

DSM Criteria

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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 Home Living Community Resources Functional Academic Skills Self Care Social/ Interpersonal Skills Self-Direction Work, Leisure, Health, and Safety

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Onset before the age of 18 **arrested development** Differential Diagnosis:

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Learning Disorders or Communication Disorders Dementia Pervasive developmental disorders

Etiology of Mental Retardation

At least 1.5 million in the US have MR

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Genetics

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SES

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Cultural deprivation

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Diet

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Drugs (Alcohol)

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Parity Mother’s Age

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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 one third 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 Chromosomal Abnormalities mostly spontaneous DS WS XXX XXY AS 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 Single gene mutations PKU RS FRX LNS DMD NF1 Phenylketonuria (1 in 10,000) many mutations in

PAH

gene for phenylalanine hydoxylase *diet* Rett Syndrome (1 in 10,000 F, lethal in M)

MECP2

, methyl-CpG-binding protein-2 Fragile X Syndrome (1 in 1,250 M, 1 in 2500 F)

FMR1

expanding triplet repeat Lesch-Nyhan Syndrome (1 in 20,000 M)

HPRT1

, hypoxanthine phosphoribosyltransferase Duchenne Muscular Dystrophy (1 in 3,500 M) huge

DMD

gene produces dystrophin doesn’t affect mice Neurofibromatosis (1 in 3,000 births) huge

NF1

gene

Distribution of IQ

Mean = 100 sd = 15 68.26% Many studies of genetic origins of low IQ, but not high IQ IQ score 95.44% 0.13% 0.13% 2.14% 13.59% 34.13% 34.13%13.59% 2.14% 50 70 85 100 115 130 145 >150 PKU FRX DMD XYY Genius RS DS LNS NF1 XXX, XXY XO +4 IGF2 WS AS, PWS promotor PM >200 "Super Genius"

Conclusions

Multiple causes of retardation suggest that intelligence

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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.