Neurobiology

Neurobiology of
of Learning
Learning and
and Memory
Memory

Lec 10:
Mental Retardation
 What
What is
is retardation?
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
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
Genetic forms:
forms: chromosomal
chromosomal
abnormalities
abnormalities
Chromosomal Abnormalities mostly spontaneous
Severe

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 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)
Mild

XO Turner’s syndrome (1 in 2,500 F)

 Genetic
Genetic forms:
forms: single-gene
single-gene mutations
mutations
Single gene mutations
PKU Phenylketonuria (1 in 10,000) many mutations in
Severe

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
Mild

doesn’t affect mice

NF1 Neurofibromatosis (1 in 3,000 births)
huge NF1 gene
Distribution
Distribution
of
of IQ
IQ
Mean = 100
Proportion of scores

68.26%
sd = 15

Many studies 95.44%

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