Project Summary

Marc G. Caron, Ph.D. (Distinguished Investigator 2005) of Duke University, will study the neurotransmitter serotonin, which has been strongly linked to depression and other psychiatric disorders. Serotonin is formed by an enzyme called tryptophan hydroxylase (TPH), and this enzyme determines the rate at which serotonin is made. Recently, a second form of this enzyme was discovered (Tph2), and may be the most critical form of the enzyme in relation to serotonin production. Dr. Caron has observed that a polymorphism (SNP) in the Tph2 gene exists in mice. He has noted that the mice with the Tph2 variant are significantly different behaviorally and also show some differences in sensitivity to antidepressants. As serotonin is implicated in many central nervous system dysfunctions, Dr. Caron will now attempt to sequence the Tph2 gene in individuals with serotonin related conditions to verify if similar polymorphisms can be identified in humans. His early results found a mutation that suggest additional functional mutations may exist in the human population that are at risk or affected with serotonin related diseases such as depression, autism and other conditions treated with antidepressants. He will now attempt to sequence the human Tph2 gene, and once functional SNPs are identified in humans, Dr. Caron will then create a mouse model with an equivalent mutation(s) and study them behaviorally, thus developing a new and improved animal model of serotonin related disorders.

Program Area: MULTIPLE FOCUS AREAS\Autism/Mood Disorders\Schizophrenia

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