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