Family Studies of Sensorimotor and Neurocognitive Heterogeneity in Autism Spectrum Disorders (ASD)
150 probands with autistic Disorder or asperger's syndrome (to be referred to as aSD for the remainder of the protocol) and their parents (150 mother/father pairs), or [Quote]trios[Quote] will participate in these studies along with 150 healthy controls (100 matched to parents, 50 matched to probands). Participants will perform three types of sensorimotor tasks: 1) Ballistic tasks in which they respond to abrupt changes in the environment, such as making a rapid eye movement or rapid grip flexion; 2) Tracking tasks in which they follow a slowly moving target with their eyes or sustain a constant grip force 3) Response suppression tasks in which they inhibit reflexive eye movements or manual responses. Psychological evaluations will be performed to evaluate social behavior, communication skills and behavioral flexibility. neuropsychological testing will be used to examine verbal abilities, nonverbal abilities, memory skills and executive functions.
Primary Variables. We will examine clinical, neurocognitive and sensorimotor functioning in family trios and healthy controls. our primary interest in this study is in sensorimotor impairments previously identified in our studies of probands with aSD and their unaffected family members. We will examine three classes of movements across oculomotor and manual motor systems: 1) ballistic movements; 2) steady-state movements, and 3) inhibitory control of motor responses. For ballistic responses, we will examine the accuracy and latency of initial movements. For sustained movements, we will examine the accuracy of open-loop (first 100 ms) and closed-loop steady-state tracking, and the latency of movement onset. For inhibitory control measures, we will examine the percentage of correctly inhibited responses and the reaction time of movements during trials when a response is made. The number of square-wave-jerks and the amount of eye gaze drift during visual fixation also will be examined.
Clinical and neurocognitive assessments. Based upon clinical diagnostic assessment and parent-report measures, probands will receive scores in the following dimensions: social skills, communication, repetitive behaviors, and overall autism severity index. Parents of probands will receive scores based upon self-report measures in the follow areas: social aloofness, pragmatic communication, and rigidity. The neuropsychology battery, consisting of various measures of language, verbal and nonverbal cognitive abilities, memory and executive functions, will provide index scores for each proband, parent, and healthy control.
We currently plan to assess family trios and healthy controls for the next three years. We anticipate that these studies will help identify promising biological intermediate phenotypes that we will study in a more comprehensive manner and with neuroimaging approaches following the completion of this grant award.
Proband Subjects. Male and female probands with ASD (Autistic Disorder or Asperger's Syndrome) must be aged between 5 to 55 years and have a Performance IQ > 80. The lower age limit was chosen to include only probands who can complete the phenotype measures. They will be included only if they have both biological parents available for study participation and both parents must be 55 years of age or under to minimize age-related changes in motor or cognitive functions. It is critical for this initial study of family trios that we examine sensorimotor phenotypes in full families, which is the rationale for the IQ and age limits, as in our experience these constraints will identify individuals who can complete all required testing. Additionally, subjects must meet the following conditions: 1) have at least a 2nd grade reading level or a level commensurate with their age and developmental status; 2) be capable of cooperating with testing; 3) be free of seizure disorder and depression; 4) be in good medical health; 5) meet DSM-IV criteria (American Psychiatric Association) for Autistic Disorder or Asperger's Syndrome on the basis of meeting autism criteria on the Autism Diagnostic Interview-Revised (ADI- R) and the Autism Diagnostic Observation Schedule-G (ADOS xG) with confirmation by expert clinical opinion 6) have no evidence of an underlying medical cause for their ASD on the basis of physical examination, neurologic history and examination, and chromosomal analysis based on existing medical records.
Parent Subjects. Parents must be 55 years old or under. Both parents will be required to participate in order to eliminate selection biases in the sample of parents used for the primary analysis, and for identification of any systematic pattern of maternal or paternal transmission of phenotypes of interest. Studying parents rather than siblings also reduces developmental effects on measures of interest that are known to be significant until 15 to 20 years of age. Testing of parents experiencing acute psychiatric problems will be deferred as this may impact performance in a state-dependent manner. The parents will fulfill the following criteria: 1) be the biological parents of the affected ASD proband; 2) be medically healthy 3) be free of medications that might affect alertness. If parents score greater than 15 on the SCQ, they will be evaluated for a possible diagnosis of ASD using the ADOS, and will be included in the study regardless of the outcome of this evaluation to have a representative sample of parents.
Healthy Control Subjects. Healthy community controls will be stratified to match the proband and parent group on age, IQ, and sex ratio. All healthy controls must be between the ages of 5 x 55 years old. Subjects will be recruited if they 1) do not meet DSM-IV criteria for any lifetime significant psychiatric or development disorder, and 2) have no family history of ASD in their first degree relatives according to our family history screening. Healthy controls must have also a history of regular school attendance and grades consistent with ability level and have Performance IQ of 80 or higher.