Imaging genetics in Autism Spectrum Disorders

Autism is a neurodevelopmental disorder that is characterized by impairments in
social interaction and communication and stereotypic patterns of behavior.
Epidemiological studies have indicated that the risk for autism spectrum
disorders (ASD) is largely genetically determined: The prevalence of autism in
siblings of individuals with autism is 2-8%, and concordance in monozygotic
twins is as high as 60-91%. However, results from genetic linkage and
association studies are inconsistent and the path by which a genetic risk for
autism can result in the development of symptoms is not yet understood. Results
from neuroimaging and post-mortem studies have indicated that functional and
structural abnormalities in several brain regions are related to autism and
related disorders.

The objective of this study is to investigate the effects of replicated and
theoretically interesting autism risk genes on brain anatomy in ASD. We will
use psychiatric genetics and gene expression patterns to predict neuroimaging
findings in ASD.

All subjects will be at least 6 years of age. Subjects will be asked to
participate in a psychological assessment (maximum duration 2.5 hrs, an
abbreviated 1 hr version will be used whenever possible) and subjects (or their
parents) will be asked to participate in a structured interview (1.5 hrs), as
well as fill out some questionnaires (45 min). For school age subjects, they
will also be asked to approach a teacher to fill out a questionnaire (20 min).
Subjects (and their parents) will be asked to provide a DNA sample for genetic
analysis, either by blood, saliva or cheekswab. Subjects will be asked to
participate in an MRI scanning session (45 min). Prior to the MRI scan, all
child subjects (6 - 12 yrs) will participate in a protocolized practice session
using an MRI simulator to desensitize them to the scanner environment, and
prevent any anxiousness or nervousness. Only after acclimating the subject to
the scanner environment, so that both the subject and parent are comfortable
with the procedure, will the subject be taken to the actual scanner. As much
time will be taken as is needed, but actual practice sessions usually take up
to 30 minutes. If the subject or the parent is uncomfortable with any aspect of
the procedure the study will be cancelled. The same procedure can be used with
older subjects if the researcher or subject feels this is advisable.

There are no known risks associated with MRI acquisition, or any of the
proposed methodologies, and we believe the impact on subjects will be minimal.
Research into the genetic basis of neurobiological deficits in ASD will improve
our insight into the pathophysiology of these disorders. Studies that elucidate
the neurobiology of ASD will ultimately facilitate future design of new and
effective ways to treat this disorder.