Project Summary

Jubao Duan, Ph.D. (Young Investigator 2005) of ENH Research Institute at Northwestern University, plans to elucidate the possible role of trace amines in the development of schizophrenia. Trace amines (TAs), including tyramine, tryptamine, ß-phenylethylamine, and octopamine, exist at low levels in mammalian brain tissues and have been speculated to play a role in psychiatric disorders. Recently, trace amine receptors (TRARs) have been identified as a novel family of G-protein coupled receptors. They also show a high degree of similarity to traditional biogenic amine receptors. One TRAR, TRAR1, was found to bind amphetamine (a chemical analog of ß-phenylethylamine), MDMA (“ecstasy”) and LSD (D-lysergic acid diethylamine) with high affinity, suggesting TAs and TRARs may be relevant to schizophrenia. TRARs also cluster at a schizophrenia linkage region, 6q23.2, in human chromosomes. Dr. Duan has evidence that polymorphisms in another TRAR, TRAR4, are associated with schizophrenia. He also has identified other TRAR4 mutations. In this project, Dr. Duan proposes developing in vitro cell models to study the effect of TRAR4 polymorphisms and mutations on gene expression, regulation, receptor ligand-binding and signal transduction. Findings should help clarify the association of TRAR4 with schizophrenia, and have important pharmacological implications for its treatment and treatment of other psychiatric disorders.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia\Molecular

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