Definition

1
Intellectual Disability
Jess P. Shatkin, MD, MPH Vice Chair for
Education NYU Child Study Center New York
University School of Medicine
2
Whats in a Name?

• Idiot
• Moron
• Feeble Minded
• Mentally Retarded
• Intellectual Disability
• AAMR
• American Assn on Intellectual and Developmental
  Disabilities (AAIDD)

3
Learning Objectives

• Participants will be able to
• Define 4 levels of severity of mental
  retardation.
• Identify the primary comorbid Axis I disorders.
• Describe 6 risk factors for mental retardation.
• Identify the 3 most common causes of mental
  retardation.
• Define behavioral phenotypes for 5 common
  mental retardation syndromes.

4
Definition

• Deficits in IQ and adaptive functioning
• IQ of 70 or below
• Measured by standard scales
• Wechsler, Stanford-Binet, Kaufman
• Impairments in Adaptive Functioning
• Effective coping with common life demands
• Ability to meet standards of independence
• Measured by standard scales
• Vineland, AAMR Adaptive Behavior Scale

5
Degrees of Severity

• Mild Mental Retardation
• IQ 50-55 to approximately 70
• Moderate Mental Retardation
• IQ 35-40 to 50-55
• Severe Mental Retardation
• IQ 20-25 to 35-40
• Profound Mental Retardation
• IQ Less than 20-25

6
AAIDD Proposed Classification

• Based upon the intensity of supports needed, as
  opposed to IQ (the traditional system)
• Intermittent Support
• Limited Support
• Extensive Support
• Pervasive Support

7
Mild Mental Retardation

• Previously referred to as educable
• Largest segment of those with MR (85)
• Typically develop social/communication skills
  during preschool years, minimal impairment in
  sensorimotor areas, often indistinguishable from
  typicals until later age
• By late teens acquire skills up to approximately
  the 6th grade level

8
Moderate Mental Retardation

• Previously referred to as trainable
• About 10 of those with MR
• Most acquire communication skills during early
  childhood years
• Generally benefit from social/vocational training
  and with moderate supervision can attend to
  personal care
• Difficulties recognizing social conventions which
  interferes with peer relations in adolescence
• Unlikely to progress beyond the 2nd grade
  academically
• Often adapt well to life in the community in
  supervised settings (performing unskilled or
  semiskilled work)

9
Severe Mental Retardation

• 3 4 of those with MR
• Acquire little or no communicative speech in
  childhood may learn to talk by school age and be
  trained in elementary self-care skills
• Can master sight reading survival words
• Able to perform simple tasks as adults in closely
  supervised settings
• Most adapt well to life in the community, living
  in group homes or with families

10
Profound Mental Retardation

• 1 2 of those with MR
• Most have an identifiable neurological condition
  that accounts for their MR
• Considerable impairments in sensorimotor
  functioning
• Optimal development may occur in a highly
  structured environment with constant aid

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Prevalence

• 1 (1 3 in developed countries)
• The prevalence of MR due to biological factors is
  similar among children of all SES however,
  certain etiological factors are linked to lower
  SES (e.g., lead poisoning premature birth)
• More common among males (1.51)
• In cases without a specifically identified
  biological cause, the MR is usually milder and
  individuals from lower SES are over-represented

12
Psychiatric Features

• No specific personality type
• Lack of communication skills may predispose to
  disruptive/aggressive behaviors
• Prevalence of comorbid Axis I disorders is 3-4
  times that of the general population
• The nature of Axis I disorders does not appear to
  be different between typicals and those w/MR
• Patients with MR and comorbid Axis I disorders
  respond to medications much the same as those
  without MR

13
Most Commonly Associated Axis I Disorders

• ADHD
• Mood Disorders
• Pervasive Developmental Disorders
• Stereotypic Movement Disorders
• Mental Disorders due to a GMC

14
Predisposing Factors

• No clear etiology can be found in about 75 of
  those with Mild MR and 30 40 of those with
  severe impairment
• Specific etiologies are most often found in those
  with Severe and Profound MR
• No familial pattern (although certain illnesses
  resulting in MR may be heritable)

15
Predisposing Factors (2)

• Heredity (5 of cases)
• Autosomal recessive inborn errors of metabolism
  (e.g., Tay-Sachs, PKU)
• Single-gene abnormalities with Mendelian
  inheritance and variable expression (e.g.,
  tuberous sclerosis)
• Chromosomal aberrations (e.g., Fragile X)
• Early Alterations of Embryonic Development (30
  of cases)
• Chromosomal changes (e.g., Downs)
• Prenatal damage due to toxins (e.g., maternal
  EtOH consumption, infections)

16
Predisposing Factors (3)

• Environmental Influences (15-20 of cases)
• Deprivation of nurturance, social/linguistic and
  other stimulation
• Mental Disorders
• Autism other PDDs
• Pregnancy Perinatal Problems (10 of cases)
• Fetal malnutrition, prematurity, hypoxia, viral
  and other infections, trauma
• General Medical Conditions Acquired in Infancy or
  Childhood (5 of cases)
• Infections, trauma, poisoning (e.g., lead)

17
Disability

• Low birth weight is the strongest predictor of
  disability
• Male children and those born to black women and
  older women in the USA are at increased risk for
  ID
• Lower level of maternal education is also
  independently associated with degree of disability

18
Etiology

• At least 500 causes now known
• Over 150 MR syndromes have been related to the
  X-chromosome
• Most common cause of MR
• Downs Syndrome (most common genetic cause)
• Fragile X Syndrome (accounts for 40 of all
  X-linked syndromes most common inherited cause)
• Fetal EtOH Syndrome (most common attributable
  cause)
• ?together these 3 account for 30 of all
  identified cases of MR

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Downs Syndrome

• Most common chromosomal abnormality leading to MR
  (1.2/1000 births)
• Nondysjunction of chromosome 21
• Relative strengths
• Visual (vs. auditory processing)
• Social functioning
• Relative weaknesses
• Language expression and pronunciation
• Generally viewed to suffer less severe
  psychopathology than other developmentally
  delayed groups
• After 40 years of age, affected individuals
  nearly always demonstrate postmortem neuronal
  defects indistinguishable from Alzheimers
  Disease

20
Behavior Psychiatric Illness in Downs

• Recent population based survey of social and
  healthcare records found
• Females had better cognitive abilities and speech
  production compared with males
• Males had more behavioral troubles
• ADHD symptoms were often seen in childhood across
  gender
• Depression was diagnosed more often in adults
  with mild/moderate intellectual impairment
• Autistic behavior was most common in those with
  profound intellectual disability
• Elderly often showed a decline in adaptive
  behavior consistent with Alzheimers
• Maatta et al, 2006

21
Downs Syndrome
22
Fragile X Syndrome

• FMR-1 gene (gt200 trinucleotide CGG repeats,
  Xq27.3)
• An example of a dynamic mutation where more
  mutations occur with successive generations
• General problems MR, mild CT dysplasia,
  macro-orchidism
• Only 50 of females with the full mutation
  demonstrate IQs in the borderline/mild MR range
  (vs. 100 of males)
• Increases the risk for ADHD, autism (20-60)
  social phobia
• Increasing deficits in adaptive and cognitive
  functioning with age
• Relative strengths
• Verbal long-term memory
• Relative weaknesses
• ST memory, VM integration, sequential processing,
  math attn

23
Fragile X Syndrome
24
Fragile X Syndrome
25
Fetal EtOH Syndrome

• Incidence gt 11000
• Irritable as infants, hyperactive as children
  (ADHD)
• Teratogen amount 2 drinks/day (smaller birth
  size), 4-6 drinks/day (subtle clinical features),
  8-10 drinks/day (full syndrome)
• General problems prenatal onset of growth
  deficiency, microcephaly, short palpebral
  fissures
• Syndrome can include
• Facial deformities (ptosis of eyelid,
  microphthalmia, cleft lip /- palate,
  micrognathia, flattened nasal bridge and filtrum,
  protruding ears)
• CNS deformities (meningomyelocele, hydrocephalus)
• Neck deformities (mild webbing, cervical
  vertebral rib abmormalities)
• Cardiac deformities (tetralogy of Fallot,
  coarctation of aorta)
• Other abnormalities (hypoplastic labia majora,
  strawberry hemangiomata)

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Fetal EtOH Syndrome
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Prader-Willi Syndrome

• Deletion in chromosome 15 (15q11-13) freq
  115000
• 60-80 w/microscopic deletion on paternal 15
  remaining PWS have 2 copies of maternal
  chromosome w/no paternal chromosome (uniparental
  disomy)
• Infantile hypotonia, hyperphagia/food seeking,
  morbid obesity, small hands/feet, mild to
  moderate MR
• Relative stability in adaptive functioning during
  adolescence and early adulthood
• Relative strengths
• Expressive vocabulary, LT memory, visual/spatial
  integration and visual memory (unusual interest
  in jigsaw puzzles)
• Relative weaknesses
• Temper tantrums, emotional lability, mood
  symptoms (dx?), anxiety, skin picking, OCD
  symptoms (gt50 OCD)

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Prader-Willi Syndrome
29
Prader-Willi Syndrome
30
Angelman Syndrome

• Severe MR, seizures, ataxia jerky arm movements
  (puppet-like gait), absence of speech, and bouts
  of laughter (aka happy puppet)
• Deletion in chromosome 15 (15q11-13)
• In contrast to PWS, all identified cases of
  deletion traced to maternal chromosome 15
• Illustrating genomic imprinting, (the fact that
  the parent of origin of the deletion at the same
  locus impacts the phenotype that is, deletion of
  paternal 15q11-13 results in Prader-Willi but
  deletion of maternal 15q11-13 results in
  Angelman.)

31
Angelman Syndrome
32
Williams Syndrome

• MR, supravalvular aortic stenosis, elfin-like
  facies, infantile hypercalcemia, and growth
  deficiency
• Deletion of elastin gene (7q11.23)
• Relative strengths
• Remarkable facility for recognizing facial
  features
• Loquacious, pseudo-mature cocktail party speech
• Relative weaknesses
• Increased risk for ADHD, Anxiety D/O

33
Williams Syndrome
34
Psychotropic Medications

• No medications identified to treat MR nor to
  address specific symptoms
• No medications are FDA approved
• Rates of medication use vary from 12 40 in
  institutions vs. 19 29 in community settings
  amongst current studies (excl anticonvulsants)
• Singh et al, 1997
• More recent review found that 22.8 of MR persons
  in group homes in the Netherlands were prescribed
  psychotropic medications
• Stolker et al, 2002

35
Stimulants

• ADHD is the most widely diagnosed psychiatric
  disorder amongst children and adolescents with MR
• Prevalence rates estimated to be 8.7 16
  (Emerson, 2003 Stromme Diseth, 2000)
• At least 20 RDBPC trials published involving MTP
  with persons with MR positive results range from
  45 66 lower than the rates found with non-MR
  population
• Positive predictors of response include IQgt50 and
  higher baseline scores on parent/teacher ratings
  of inattention and activity level
• Limited data on other treatments for ADHD
  symptoms
• Handen et al, 2006

36
Antidepressants Sertraline/Zoloft

• No DBPC studies w/Sertraline in patients w/MR
• One open label study of children with PDD noted
  improvements in anxiety and agitation (Steingard
  et al, 1997)
• Luiselli et al (2001) noted a case of one adult
  w/severe MR who showed improvement in SIB with
  Sertraline
• In the adult MR/PDD population, Sertraline has
  been found to result in clinically significant
  improvement of SIB and aggression (Hellings et
  al, 1996 McDougle et al, 1998)

37
Antidepressants Fluoxetine/Prozac

• Among 15 published case reports and 4 prospective
  open label trials involving children and adults
  with MR and/or PDD, decreases in SIB,
  irritability, or depressive symptoms were noted
  (with the exception of two studies) for the
  majority of subjects treated with fluoxetine
  (Aman et al, 1999)
• Among the negative studies, some individuals
  discontinued fluoxetine due to increased
  aggression, agitation, and hypomanic behavior
• One open label study of fluoxetine in 128
  children with MR/PDD, 3-8 y/o, reported an
  excellent response in 17, a good response in
  52, and a fair/poor response in 31 (DeLong et
  al, 2002)

38
Antidepressants Fluvoxamine/Luvox

• One open label study of 60 adults w/MR
  (200-300mg/d) reported a significant reduction in
  ratings of aggression after 3 weeks of treatment
  (La Malfa et al, 2001)
• McDougle et al (1996) conducted a DBPC study of
  fluvoxamine in 30 adults w/PDD and found
  significantly reducted aggression and repetitive
  thoughts/behavior
• McDougle (1998) also reported significant side
  effects and minimal clinical improvement in a
  DBPC study of children with PDD and symptoms of
  ritualistic and repetitive movements
• Fukuda et al (2001) conducted a DBPC trial in 18
  children w/PDD where clinical global ratings
  improved for half of the subjects and significant
  gains were noted in eye contact and language use

39
Antidepressants Paroextine/Paxil

• Davanzo et al (1998) demonstrated reductions in
  aggression (but not SIB) in 15 adults with MR in
  an open label study, but effects did not last
  beyond a one month period
• A retrospective chart review of 12 adults with MR
  found only 1/3 of subjects were minimally or
  much improved in domains of aggression,
  property destruction, or SIB (Branford et al,
  1998)
• Masi et al (1997) treated 7 adolescents with MR
  and MDD after 9 weeks of treatment, 4 subjects
  no longer met DSM-IV criteria for MDD

40
Antidepressants Citalopram/Celexa

• Verhoeven et al (2001) found citalopram effective
  in an open label trial of 20 adults with MR and
  MDD, demonstrating a moderate to marked
  improvement in 12 of 20 patients on CGI after 6
  months

41
Antipsychotics in the Treatment of MR

• The typical antipsychotics have long been
  prescribed for disorders other than psychosis in
  patients with MR, including aggression,
  hyperactivity, antisocial behavior, sterotypies,
  and SIB
• The atypical antipsychotics are now being
  increasingly used b/c of the belief that they
  carry a decreased side effect profile

42
Antipsychotic Clozapine/Clozaril

• Found effective in treating resistant psychosis
  in adults with MR (Antochi et al, 2003)

43
Antipsychotic Risperidone/Risperdal

• Efficacious in both children and adults with MR
  in controlling hyperactivity, irritability,
  aggressive behavior, SIB, and repetitive
  behaviors (Aman Madrid, 1999 Hellings, 1999
  Turgay et al, 2002 Van Bellinghen DeTroch,
  2001)
• A DBPC trial in 118 children w/MR, 5-12 y/o,
  found 53.8 were responders vs. 7.9 w/placebo
  (Aman et al, 2002)
• Similarly, McCracken et al (2002) reported a 69
  response rate (vs. 12 w/placebo) among 101
  children w/PDD, most of whom had comorbid MR

44
Antipsychotic Olanzapine/Zyprexa

• McDonough et als (2000) open label study of 7
  adults w/MR documented improvement in SIB in 57
  of subjects and worsening effects in 14
• Similarly, a chart review of 20 adults w/MR found
  significant decreases in global challening
  behaviors and specific target behaviors, such as
  aggression, SIB, and destructive behaviors
  (Barnhill Davis, 2003)
• Handen Hardan (2006) conducted a prospective
  open label trial in 16 adolescents w/MR and found
  12 of 15 experienced a 50 or greater decrease on
  behavior ratings assessing irritability
• Robust clinical effects noted in Friedlander et
  als chart review of adolescents and young adults
  w/MR (2001)

45
Antipsychotic Quetiapine/Seroquel

• Hardan et al (2005) reported efficacy in the
  treatment of hyperactivity, inattention, and
  conduct problems in 10 children and adolescents
  w/MR
• Martin et al (1999) found quetiapine poorly
  tolerated in a study of boys with autism

46
Antipsychotic Ziprasidone/Geodone

• A case series of children and adolescents w/PDD
  reported decreased aggression and irritability
  (McDougle et al, 2002)
• Cohen et al (2003) switched 40 adults w/MR to
  ziprasidone from other antipsychotics and noted
  an improved side effect profile w/either no
  change or improvement in maladaptive behavior in
  72 of subjects

47
Antipsychotic Aripiprazole/Abilify

• Stigler et al (2004) found aripiprazole
  beneficial in treating aggression, agitation, and
  SIB in five children w/PDD
• Staller (2003) reported decreased irritability,
  anxiety, and preoccupations in an adult
  w/Aspergers D/O

48
Alpha-2 Agonists Guanfacine/Tenex
Clonidine/Catapres

• Frankhauser et al (1992) demonstrated the
  efficacy of clonidine in the treatment of
  hyperactivity in children w/PDD
• Posey et al (2004) conducted a chart review of 80
  children w/PDD who had been treated with
  guanfacine 24 of the sample evidenced decreased
  hyperactivity, inattention, and tics