Intellectual Disability

Jess P. Shatkin, MD, MPH

Vice Chair for Education
NYU Child Study Center
New York University School of Medicine

Whats 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) Downs 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

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

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

Downs 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 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)

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/Aspergers 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