Intellectual Disability

Intellectual Disability

Jess P. Shatkin, MD, MPH

Vice Chair for Education

NYU Child Study Center

New York University School of Medicine

WhatWhat’’s in a Name?s in a Name?

IdiotMoronFeeble MindedMentally RetardedIntellectual DisabilityAAMR

– American Assn on Intellectual and Developmental Disabilities (AAIDD)

Learning ObjectivesLearning 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.

DefinitionDefinition

Deficits in IQ and adaptive functioningIQ 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 SeverityDegrees 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 ClassificationAAIDD 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 RetardationMild 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 RetardationModerate 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 RetardationSevere Mental Retardation

3 – 4% of those with MRAcquire 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” wordsAble to perform simple tasks as adults in closely

supervised settingsMost adapt well to life in the community, living

in group homes or with families

Profound Mental RetardationProfound Mental Retardation

1 – 2% of those with MRMost have an identifiable neurological

condition that accounts for their MRConsiderable impairments in sensorimotor

functioningOptimal development may occur in a highly

structured environment with constant aid

PrevalencePrevalence

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 FeaturesPsychiatric FeaturesNo specific personality typeLack of communication skills may predispose to

disruptive/aggressive behaviorsPrevalence 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/MRPatients with MR and comorbid Axis I disorders

respond to medications much the same as those without MR

Most Commonly Associated Most Commonly Associated Axis I DisordersAxis I Disorders

ADHDMood DisordersPervasive Developmental DisordersStereotypic Movement DisordersMental Disorders due to a GMC

Predisposing FactorsPredisposing 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)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)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, traumaGeneral Medical Conditions Acquired in Infancy

or Childhood (5% of cases)– Infections, trauma, poisoning (e.g., lead)

DisabilityDisability

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

EtiologyEtiology 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

DownDown’’s Syndromes 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 DownsBehavior & 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

DownDown’’s Syndromes Syndrome

Fragile X SyndromeFragile 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 SyndromeFragile X Syndrome

Fragile X SyndromeFragile X Syndrome

Fetal EtOH SyndromeFetal 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 SyndromeFetal EtOH Syndrome

Prader-Willi SyndromePrader-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 SyndromePrader-Willi Syndrome

Prader-Willi SyndromePrader-Willi Syndrome

Angelman SyndromeAngelman 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 SyndromeAngelman Syndrome

Williams SyndromeWilliams SyndromeMR, 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 SyndromeWilliams Syndrome

Psychotropic MedicationsPsychotropic MedicationsNo medications identified to treat MR nor to

address specific symptomsNo medications are FDA approvedRates 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

StimulantsStimulants 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 ®Antidepressants: Sertraline/Zoloft ®No DBPC studies w/Sertraline in patients w/MROne 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®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®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®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®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 Antipsychotics in the Treatment of MRTreatment 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®Antipsychotic: Clozapine/Clozaril®

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

Antipsychotic: Antipsychotic: Risperidone/Risperdal®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®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®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®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®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: Alpha-2 Agonists: Guanfacine/Tenex® & Guanfacine/Tenex® & Clonidine/Catapres®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