Clinical and Immunological Investigations of Subtypes of Autism
Condition: Autism Spectrum Disorders; Seizures
MeSH terms: Seizures; Autistic Disorder; Autism Spectrum Disorder
Study type: Observational

Summary: 
      The purpose of this study is to learn more about autism and its subtypes. Autism is a
      developmental disorder in which children have problems with communication and social skills
      and display restricted interests and repetitive behaviors.

      This study has several goals. One aim is to look at types of autism that are known, such as
      the regressive subtype, (where skills are lost). We will explore whether there is a unique
      change in immune functioning related to this subtype. Another aim is to serve as one of the
      sites that will pilot a larger natural history study, entitled Autism Phenome Project. The
      goal is to further understand autism by identifying other subtypes.

      We will look at several types of medical issues that may be related to autism, including
      immunologic problems. Children will be followed over the course of several years. We aim to
      capture medical problems that may be related to autism as they develop, and study outcomes in
      areas such as behavior and language, in order to explore known and new subtypes of autism.

      Normally developing children (aged 1) with autism (age 1, and developmental delays other than
      autism (age 1), may be eligible for this study.

      Depending on each child's study group and age, participants may undergo the following tests
      and procedures:

      Baseline Visit

        -  Medical and developmental history, physical examination, psychological, cognitive and
           medical tests to assess symptoms of autism or other developmental disorders, photographs
           of the child's face, collection of hair, urine and baby teeth samples. If available,
           hair samples from the baby's first haircut and from the biological mother's hair are
           also collected.

        -  Overnight electroencephalogram (EEG): A special cap with electrodes is placed on the
           child's head to measure brain waves (brain electrical activity) while the child sleeps
           in the hospital overnight. Healthy volunteers do not undergo this procedure.

        -  Magnetic resonance imaging (MRI) scan: The child stays in the scanner, lying still for
           10 to 15 minutes at a time. Since it may be difficult for the child to lie still, the
           test may be scheduled for a time when the child is likely to be sleepy, or the child may
           be sedated.

        -  Lumbar puncture (for children in the autism). This test and the MRI may be done under
           sedation.

      Follow-Up Visits

      Follow-up visits are scheduled at different intervals, depending on study group, age and
      aspect of the study the child is enrolled in. The visits include a short interview session
      with the child's caregiver and assessment of the child's development and behavior. Some of
      the assessment measures used during the baseline examination are repeated, including symptoms
      ratings, behavioral tests and a blood test. For some children, the final visit will include
      repeats of the medical procedures.
    

Detailed description: 
      Objective:

      The current investigation focuses on finding meaningful subtypes of autism. Our objectives
      include using comprehensive and longitudinal medical assessments and behavioral testing to
      find subgroups of children with autism with profiles that comprise distinct
      biological/behavioral phenotypes.

      Specific goals include determining if there is a unique alteration in immune function among
      autistic children with a regressive clinical course, and identifying autism-specific sleep
      and electroenchelalogram (EEG) abnormalities, and other potential biomarkers.

      Study Population:

      We are conducting a longitudinal natural history study of 140 children with autism, 12 to 84
      months of age at study entry. We also are following as many as 75 typically developing
      children, and 50 children with Developmental Delay to serve as age-/sex-matched controls.

      Design:

      Systematic prospective evaluations are being utilized to determine diagnostic and functional
      outcomes, and evaluate behavioral, medical and immunologic functioning. These evaluations
      include comprehensive medical history, behavioral assessment, physical and neurologic
      examination, polysomnography (PSG) and EEG, and blood work for laboratory assays. Baseline
      evaluations also included MRI and lumbar puncture (the latter was only subjects with autism).
      In any investigation of behavioral outcomes and potential biomarkers, repeated assessments
      are necessary to determine whether findings are due to state versus trait alterations. Thus,
      key elements of the assessments are repeated every 6 to 12 months, depending on the child s
      age.

      Outcome Variables:

      Measures of autism symptoms and severity, along with cognitive and adaptive behavior
      profiles, will be used as behavioral outcome variables.

      Results of physical and neurological examinations, genetic testing, EEGs, polysomnograms, MRI
      scans and laboratory assays of blood and CSF will be tested for their utility as biomarkers
      of autism s core symptoms or identification of etiologically related subgroups of patients.
    

Observational model: Cohort
Time perspective: Prospective
Keywords: Neurodevelopmental Disorders; Neurological Disorder; Children- Onset; Children; Pervasive Developmental Disorder; PDD; Autism; Healthy Volunteer; HV