Methylphenidate for Attention Deficit Hyperactivity Disorder and Autism in Children

Attention Deficit Hyperactivity Disorder (ADHD) is a major comorbid psychiatric disorder in
children with Autism Spectrum Disorders (ASD) that significantly undermines behavioral,
social, and emotional adjustment. Although the Diagnostic and Statistical Manual of Mental
Disorders (DSM-IV) does not specifically allow for a comorbid diagnosis of ADHD with ASD,
many children with an ASD manifest symptoms of ADHD and are treated for it with stimulants
or other medication. The few studies on ADHD in ASD have not consistently established its
cognitive and behavioral manifestations, or the optimal parameters for treatment. The
proposed project will address these issues through studies of cognitive and behavioral
functioning in children with ASD, with and without ADHD, and through a study of medication
treatment of ADHD symptoms in autism.

Two groups of participants between the ages of 7 to 12 will participate in the initial phase
of the study to examine the differences in children who have an Autism Spectrum Disorder
with or without additional symptoms of ADHD. In one group, participants will qualify for a
diagnosis of an Autism Spectrum Disorder (Autistic Disorder, Asperger's Disorder, and
Pervasive Developmental Disorder-Not Otherwise Specified) and will also have symptoms of
ADHD (ASD/ADHD), while in the second group, participants will have an Autism Spectrum
Disorder, without symptoms of ADHD (ASD/non-ADHD group). All participants will undergo an
initial psychological testing session that includes standardized measures of intellectual,
adaptive behavior, language, behavioral, and emotional functioning, along with standardized
diagnostic measures to confirm their diagnoses of ASD and/or ADHD (Visit 1). Children with
intelligence quotients (IQs) below 50 or greater than 130 or with major sensory, motor,
neurological, genetic, or psychiatric disorders that may interfere with testing will be
excluded. The participants who meet eligibility criteria will complete computerized tasks of
attentional functioning in a second visit (Visit 2).

A subset of the children from the ASD/ADHD group (N=24) will be invited to participate in a
six-week randomized double-blind, placebo-controlled treatment trial using various doses
(low, medium, or high dose) of methylphenidate (MPH). Children who are invited to
participate in the treatment trial will be those who qualified based on the initial phase
and who do not have any physical contraindications to MPH (e.g., history of MPH
intolerance). In each week of the treatment trial, the child will take one of the three
doses of MPH or a placebo. At the end of each week the child will be brought into the clinic
by the parent for a medical check-up, parent interviews about the child's behavior and
functioning that week, and computerized cognitive testing. Additionally, the child's parent
and teacher will be asked to complete questionnaires about the child's behavior each week,
so that the child's home and school behaviors at each MPH dose can be assessed.

Inclusion Criteria:

Autism/ADHD Group:

- DSM-IV diagnosis of autistic disorder, as per the Autism Diagnostic Interview-Revised
(ADI-R) and the Autism Diagnostic Observation Schedule (ADOS)

- Child manifests current symptoms of ADHD

Autism/non-ADHD Group:

- Meets the diagnostic criteria for autism, as above, but does not meet the diagnostic
criteria for ADHD

Exclusion Criteria:

In both groups, exclusion criteria will include:

- Sensory or motor deficits sufficient to interfere with testing (e.g., blindness,
severe cerebral palsy)

- Serious neurological disorders (e.g., epilepsy, stroke)

- Down syndrome, fragile X syndrome, Tourette syndrome, or fetal alcohol syndrome

- Bipolar disorder or a family history of bipolar disorder in a first-degree relative

- Other serious psychopathology that resulted in psychiatric hospitalization (e.g., for
psychotic episode). The investigators will screen for this using the Diagnostic
Interview for Children and Adolescents (DICA)-IV, and getting a complete
developmental/medical history

- Serious physical handicaps that would interfere with performance on laboratory tasks

- IQ less than 50 and greater than 130

- Verbal mental age (VMA) less than 36 months (to exclude participants unable to
understand simple task instructions)

In the autism/ADHD group, further exclusion criteria apply to the MPH trial:

- History of intolerance to MPH

- Weight less than 20 kg or greater than 59 kg (less than 44 pounds or greater than 130
pounds)

- Concomitant use of dextroamphetamine preparations (Dexedrine, Dextrostat), mixed
amphetamine salts (Adderall XR), other MPH preparations (e.g., Concerta, Metadate);
venlafaxine, bupropion, atomoxetine, guanfacine, modafinil.

- Concomitant use of any herbal preparations

- Medical condition for which stimulants are contraindicated (e.g., high blood
pressure)

- Past treatment failure on a methylphenidate trial