Cognitive Disabilities

1. Cognitive Disabilities

2. Mental Retardation • APA Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV): • Sub-average intellectual functioning • Onset before 18 years • Limited adaptive (life) skills

3. Four Levels of Mental Retardation • 1. Mild: IQ 50-70 • -about 85% of all MR individuals • -most can hold a job and live independently • -familial (runs in families) • 2. Moderate: IQ 35-50 • -about 8% of all MR individuals • -most institutionalized or group homes • -good self-care and simple language skills • -not familial

4. Four Levels of Mental Retardation • 3. Severe: IQ 20-35 • -about 4% of all MR individuals • -require considerable supervision • -some self-care and language comprehension skills, • limited speech • -not familial • 4. Profound: IQ < 20 • -about 2-3% of all MR individuals • -most institutionalized • -limited if any language comprehension, usually no speech • -not familial

5. Two Types of Mental Retardation • Cultural/Familial: • Attributable to the combined effects of the multiple genetic and environmental factors that contribute to variation in IQ throughout its normal range Organic: Attributable to a major traumatic event that causes irreversible damage to the developing CNS

6. IQ Distribution

7. Evidence for Two Types of MR

8. Evidence for Familiality of Mild MR • Reed & Reed (1965): • -studied 80,000 relatives of 289 individuals with MR • -20% of children with one mildly MR parent were mildly MR • -about 50% of children with two mildly MR parents were • mildly MR • Nichols (1984): • -studied IQs of 15 MZ and 23 DZ pairs in which at least 1 • twin had mild MR • -concordance for MR: MZ = 75%, DZ = 46% • Other twin studies: • -low IQ is at least as heritable as is IQ in the normal range

9. Factors Contributing to Organic MR (% are very approximate) • Specific Environmental Factors:10-30% • -teratogens (alcohol) • -peri- and post-natal trauma (Asphyxia) • -fetal infections (Rubella) • -head injuries • Specific Genetic Factors: 50-60% • -chromosomal disorders (Down Syndrome) • -genetic disorders (PKU, RETT, Lesch-Nyhan)

10. Down Syndrome • single most important cause of MR: occurs in about 1/1000 births • average IQ: 55 but a wide range exists • -top 10% have IQ’s in the lower end of normal range • many of those who reach age 45 will have some form of dementia • caused by a trisomy of chromosome 21 • (i.e. 3 rather than 2 copies of chromosome 21 are inherited) • occurs more often in offspring of older mothers, presumably due • to activation of eggs that have been dormant for decades

11. Normal Set of Chromosomes (Female)

12. Chromosomes of a Male with Trisomy 21

13. Phenylketonuria (PKU) • occurs in about 1/10,000 births • if untreated, IQ’s often < 50 though some near normal • PKU is a single-gene recessive disorder • easily detected (at birth) and treated by a diet low in phenylalanine • (found in red meats and other foods) • even with treatment, PKU individuals are somewhat below • average IQ • excellent example of something which is entirely ‘genetic’ being • largely treatable by ‘environmental’ intervention

14. Rett Syndrome • second most common cause of MR in females • (after Down Syndrome) • occurs in about 1/10,000 females • shows few effects in infancy • by age 5, most affected girls cannot stand, talk, or use hands and • will show autistic-like behavior • due to these symptoms, an accurate assessment of intelligence is • essentially impossible

15. Other Genetic or Chromosomal Disorders Contributing to MR More than 100 genetic disorders include MR among their symptoms: • Fragile X Syndrome XXY Male Syndrome • Duchenne Muscular Dystrophy XXX Female Syndrome • Neurofibromatosis Type 1 XYY Male Syndrome • Angelman Syndrome XO Female (Turner’s) • Williams Syndrome

16. Fragile X Syndrome • second most common cause of MR after Down Syndrome • twice as common in males (1/1250) than females (1/2500) • most fragile X males have moderate MR, many only mild, • some normal IQ • only about half of fragile X females are affected because one of • the two X chromosomes inactivates • typically 6 to 54 CGG triplet repeats on the X chromosome • fragile X chromosome may have > 200 such repeats • - ‘fragile’: this many repeats literally makes it break easily. • neurobiological research may one day counteract its effects, which • molecular genetic research is beginning to understand

17. Duchenne Muscular Dystrophy • an X-linked recessive disorder found in 1/3500 males • average IQ of affected males is 85 • verbal abilities typically more impaired than nonverbal • neuromuscular disorder that usually leads to death by 20 years • it is not known how the DMD gene affects IQ

18. Sex Chromosome Abnormalities • an X-linked recessive disorder found in 1/3500 males • average IQ of affected males is 85 • verbal abilities typically more impaired than nonverbal • neuromuscular disorder that usually leads to death by 20 years • it is not known how the DMD gene affects IQ

19. Sex Chromosome Abnormalities • XXY Male Syndrome • -occurs in about 1/750 male births • -somewhat lower than average IQ, poor academic • -achievement, language problems • XXX Female Syndrome • -occurs in about 1/1000 female births • -average IQ=85 • -speech therapy often required

20. Sex Chromosome Abnormalities • XYY Male Syndrome • -occurs in about 1/1000 male births • -often require speech therapy, academic problems, higher • incidence of juvenile delinquency • XO Female (Turner’s) Syndrome • -occurs in about 1/2500 female births (but 99% miscarry) • -surviving females have just one X chromosome • -short stature, abnormal sexual development, often infertile • -normal verbal IQ but performance IQ is below average

21. Reading Disability (Dyslexia) • the primary disability in about 80% of children with a • diagnosed learning disorder -Dyslexic children read slowly and with poor comprehension • -familial and likely heritable: • -among 250 twin pairs in which at least one was dyslexic, • MZ concordance = 66%, DZ = 36% • -DF extremes analysis (group heritability) -the first QTL for any human disorder was reported and replicated for reading disability

22. Group Heritability • An estimate of the extent to which the difference between average and extreme scoring individuals is attributable to genetic and/or environmental factors • Example: Reading disabilities

23. GROUP HERITABILITYReading Disabilities

24. GROUP HERITABILITYReading Disabilities group h2 = 0 x RD x MZ & DZ

25. GROUP HERITABILITYReading Disabilities group h2 = 1.0 x RD & MZ x DZ

26. GROUP HERITABILITYReading Disabilities Defries & Fulker (1985) group h2 = .28 x RD -2.8 x MZ -2.0 x DZ -.1.6

27. Estimating Group Heritability 1.Compute ratio of reading scores: MZ = 2.0/2.8 = .71 DZ = 1.6/2.8 = .57 2.Group Heritability = 2(MZ - DZ) = 2(.71 - .57) = .28 3.Therefore, 28% of the difference between RD and general population is attributable to genetic factors  .71 - .28 = 43% of the difference is attributable to shared environmental factors  the remaining 29% is attributable to nonshared environmental factors

28. Comparing Heritability and Group Heritability • (individual) h2 for reading ability = .50 • group h2 for reading disability = .28 Since these differ, this indicates that the genetic etiology of reading disabilities is different from that of the normal distribution of reading scores