Intellectual Disability

Jess P. Shatkin, MD, MPH

Vice Chair for Education
NYU Child Study Center
New York University School of Medicine
 What’s in a Name?
 Idiot
 Moron
 Feeble Minded
 Mentally Retarded
 Intellectual Disability
 AAMR
– American Assn on Intellectual and
Developmental Disabilities (AAIDD)
 Learning Objectives
 Participants will be able to:
1) Define 4 levels of severity of mental retardation.
2) Identify the primary comorbid Axis I disorders.
3) Describe 6 risk factors for mental retardation.
4) Identify the 3 most common causes of mental
retardation.
5) Define behavioral phenotypes for 5 “common”
mental retardation syndromes.
 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
 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
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
 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
 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)
 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
 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
 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 (1.5:1)
 In cases without a specifically identified biological
cause, the MR is usually milder; and individuals
from lower SES are over-represented
 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
 Most Commonly Associated
Axis I Disorders

 ADHD
 Mood Disorders
 Pervasive Developmental Disorders
 Stereotypic Movement Disorders
 Mental Disorders due to a GMC
 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)
 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)
 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)
 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
 Etiology
 At least 500 causes now known
 Over 150 MR syndromes have been related to
the X-chromosome
 Most common cause of MR:
(1) Down’s Syndrome (most common genetic cause)
(2) Fragile X Syndrome (accounts for 40% of all X-
linked syndromes; most common inherited cause)
(3) Fetal EtOH Syndrome (most common attributable
cause)
together these 3 account for 30% of all identified
cases of MR
 Down’s 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 Alzheimer’s Disease
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 Alzheimer’s
• Maatta et al, 2006
Down’s Syndrome
 Fragile X Syndrome
 FMR-1 gene (>200 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
Fragile X Syndrome
Fragile X Syndrome
 Fetal EtOH Syndrome
 Incidence > 1:1000
 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)
Fetal EtOH Syndrome
 Prader-Willi Syndrome
 Deletion in chromosome 15 (15q11-13); freq 1:15000
 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 (>50% OCD)
Prader-Willi Syndrome
Prader-Willi Syndrome
 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.)
Angelman Syndrome
 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
Williams Syndrome
 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
 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 IQ>50 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
 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)
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)
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
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
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
 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
Antipsychotic: Clozapine/Clozaril®

 Found effective in treating resistant

psychosis in adults with MR (Antochi et al,
2003)
 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
Antipsychotic: Olanzapine/Zyprexa®
 McDonough et al’s (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 al’s chart
review of adolescents and young adults w/MR (2001)
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
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
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/Asperger’s D/O
 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