A Pharmacogenetic Study of Escitalopram in Autism

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DESCRIPTION (provided by applicant): The study of the interaction between pharmacological response and genetic constitution is increasingly being recognized as making significant contributions to the clinical management of psychiatric illness. Such information is likely to be especially useful for a disease process like autistic disorder where the majority of current research strongly suggests a complex genetic basis involving multiple loci. There is also an enormous amount of research that implicates the serotonergic system in autistic disorder, and these patients have been found to be responsive to medications that manipulate this system. Elucidating the exact relationship(s) between genes and drug response in these patients remains a considerable challenge. The candidate proposes training and development in the investigation of the interplay between genetics and pharmacological response that will provide a foundation for addressing these problems. The candidate, an Assistant Professor in the Department of Psychiatry at the University of Chicago, completed a child psychiatry fellowship at the University of Chicago, and has been trained in the assessment and pharmacological treatment of autistic patients. The specific aims of this proposal are: 1) to develop expertise in genetics and psychopharmacology that will foster the ability to undertake independent research; 2) to test the hypothesis that dose response to serotonin reuptake inhibitors is a function of the allelic variation of the serotonin transporter in autistic subjects. The training program will include supervision under the direction of experts in the fields of the Pervasive Developmental Disorders, genetics, statistics, psychopharmacology, and epidemiology. The program includes beginning the collection of data during the second year, allowing the candidate to implement the skills developed during the training period. A sample of 110 children and adolescents with autistic disorder will be recruited during this year, and their response to a serotonin reuptake inhibitor assessed. By completing the proposed development and training program, the award candidate will attain a comprehensive knowledge base in the area of pharmacogenetic research, and will pursue an independent program of research aimed at identifying the role of serotonin in the response of autistic subjects to serotonergic agents.