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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 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
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
Chromosomal Abnormalities mostly spontaneous
Down’s Syndrome (1 in 1,000) Trisomy 21
Most develop Alzheimer’s & lethal
WS William’s 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-Willi Syndrome (1 in 15,000) from father
same locus as AS, but SNRPN gene affected
XYY XYY Syndrome (1 in 1,000 M)
XO
Turner’s syndrome (1 in 2,500 F)
DS
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
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
"Super
Genius
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.