Clinical and Genetic Study of Autism Spectrum Disorder

Autism is a pervasive neurodevelopmental disorder with prominent reciprocal social and communication impairment and restricted repetitive behavior or interest. Based on the number of symptoms and functional impairment, autistic disorder, Asperger disorder, and atypical autism (or PDDNOS) are conceptualized as the autism spectrum disorder (ASD). Most recent survey estimated the prevalence of narrow diagnosis of autistic disorder to be around 0.1% to 0.2%, and 0.59 % to 0.63% for ASD, with a four-fold male predominance. Due to high heritability (> 0.9), high family recurrence risk (λ = 60), and severe impairment without effective prevention and treatment available for ASD, this disastrous disease has been prioritized for molecular genetic study from public health perspective. The proposed research is the first systematic approach combining clinical and molecular genetic study of ASD involving multi-sites and three research cores: assessment core (by Gau SS and Wu YY), molecular genetics core (by Chen CH), and data/statistics core (by Gau SS).

The long-term objective of this study is to establish clinical and genetic database of autism and their family for etiology study, exploration of pathogenesis, and developing new treatment. The specific aims are:

1. to establish the psychometric properties of three Chinese versions of rating scales for ASD: SCQ, SRS, and ABC;
2. to collect clinical, neuropsychological, and genetic data of ASD probands and their family and
3. to identify the genetic variants close to etiological genes of ASD in a Taiwanese sample using candidate gene case-control association study design (e.g., Neuroligin gene family, MeCP2 gene, and FOXP2 gene, parent trio and population-based studies) and whole genome linkage analysis for multiplex families.

After well-preparation of instruments, DNA collection procedure, and assessor's training in the first 6 months, we will recruit 40, 170, and 90 ASD families in the first, second, and third year of the project, respectively. The instruments include the ADI-R, ADOS, K-SADS-E, SCQ, SRS, and ABC for measuring autistic psychopathology; WISC-III, MSEL and PPVT for cognitive ability; CPT, CANTAB, and WCST for neuropsychological functioning, and MRI, MRS, and DSI for brain imaging study.

We anticipate the establishment of the database of 300 ASD families, completion of the mutation screening of several candidate genes, and determination of their association with ASD and its intermediate phenotype in our sample. The identification of susceptible genes for ASD would be a major breakthrough in child psychiatry because this revelation would facilitate the scientific diagnosis of autism and as a result, it would shed light on the pathogenesis of autism and contribute to the development of the novel, specific and effective treatment of this devastating disease.