Neurobiology of Learning and Memory Prof. Anagnostaras

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Neurobiology of Learning and Memory Prof.
Anagnostaras

• Lec 10
• Mental Retardation

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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

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Etiology of Mental Retardation

• At least 1.5 million in the US have MR
• Genetics
• SES
• Cultural deprivation
• Diet
• Drugs (Alcohol)
• Parity
• Mothers Age
• Prenatal factors

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MR and Mothers 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 isnt heritable doesnt mean
it isnt genetic!
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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
6th 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
2nd grade level difficulties recognizing
social conventions and may interfere with
pure relationships needs to be supervised
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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
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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 Downs Syndrome (Trisomy 21) Fragile X
Syndrome
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Low Heritability of Severe Retardation
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Genetic forms chromosomal abnormalities
Chromosomal Abnormalities mostly spontaneous DS
Downs Syndrome (1 in 1,000) Trisomy 21 Most
develop Alzheimers lethal WS Williams
Syndrome (1 in 25,000) - Chr 7 LimK XXX Triple X
Syndrome (1 in 1,000 F) XXY XXY Male Syndrome (1
in 750 M) AS Angelman Syndrome (1 in 25,000) from
mother 15q11, UBE3A, GABR3 affected PWS Prader-Wi
lli Syndrome (1 in 15,000) from father same
locus as AS, but SNRPN gene affected XYY XYY
Syndrome (1 in 1,000 M) XO Turners syndrome (1
in 2,500 F)
Severe
Mild
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Genetic forms single-gene mutations
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 doesnt affect mice NF1 Neurofibromat
osis (1 in 3,000 births) huge NF1 gene
Severe
Mild
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Distribution of IQ
Mean 100 sd 15
68.26
Proportion of scores
Many studies of genetic origins of low IQ, but
not high IQ
95.44
0.13
0.13
13.59
34.13
34.13
13.59
2.14
2.14
50 70 85 100 115 130
145
IQ score
gt200 "Super Genius"
gt150 Genius
PKU RS DS WS
FRX LNS
DMD NF1 XXX, XXY AS, PWS
XYY XO
4 IGF2 promotor PM
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Conclusions
Multiple causes of retardation suggest that
intelligence is complexgtgt 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.