Abraham A. Palmer

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Abraham A. Palmer, Ph.D.
Assistant Professor
Department of Human Genetics
Committee on Neurobiology
Committee on Genetics

Lab webpage

Identification of genes that modulate sensitivity to drugs of abuse

Genetic variation contributes to individual differences in the risk for a variety of psychiatric and other common diseases. For the common psychiatric diseases, multiple genes work in concert to confer risk, and interact with one another, as well as the environment, to determine the observed phenotype. Identifying these genes, as well as understanding their complex interactions, promises to revolutionize the diagnosis and treatment of psychiatric diseases. Our research uses mice as a model genetic system to identify specific genes that contribute to heritable disorders.

Genetic determinants of sensitivity to methamphetamine (MA) in mice and humans. Individual differences in the sensitivity to drugs of abuse are controlled by both genetic and environmental factors. The genetic variants associated with differential sensitivity to abused drugs may partially underlie genetic liability for drug abuse. We have integrated QTL mapping with gene expression analysis and used these two approaches to identify genes that are associated with differential sensitivity to AM. Preliminary work with Harriet de Wit (Psychiatry) has established that at least one of these genes also regulates sensitivity to MA in human subjects who were administered MA in a controlled laboratory setting.

Translational genetic approach to fear and anxiety. Fear learning and anxiety disorders may be regulated by common genetic substrates. We selectively bred mice for high or low levels of fear learning to identify both QTLs for fear learning and gene-expression differences between the high and low selected lines. We have also shown that selection altered other aspects of fear and anxiety-like behavior. Candidate genes identified by this approach will be screened against several large human samples that have been phenotyped for fear and anxiety related traits.

References

Palmer, A.A., Printz, D.J., Butler, P.D., Dulawa, S.C., Printz, M.P. (2004) Prenatal Protein Deprivation in Rats Induces Changes in Prepulse Inhibition and NMDA Receptor Binding. Brain Research, 996:193-201.

Palmer, A.A., Sharpe, A.L., Burkhart-Kasch, S., McKinnon, C.S., Coste, S.C., Stenzel-Poore, M.P., Phillips, T.J. (2004) Corticotropin-Releasing Factor Overexpression Decreases Ethanol Drinking and Increases Sensitivity to the Sedative Effects of Ethanol. Psychopharmacology, 176:386-397.

The Complex Trait Consortium. (2004) The Collaborative Cross, a community resource for the genetic analysis of complex traits. Nature Genetics, 36: 1133-1137.

Palmer, A.A., Verbitsky, M., Suresh, R., Kamens, H.M. Reed, C.L., Li, N., Burkhart-Kasch, S., McKinnon, C.S., Belknap, J.K.; Gilliam, T.C., Phillips, T.J. (2005) Gene Expression Differences in Mice Divergently Selected for Methamphetamine Sensitivity. Mammalian Genome, 16:291-305.

Yonan, A.L., Palmer, A.A., Gilliam, T.C. Hardy-Weinberg Disequilibrium Identified Genotyping Error of the Serotonin Transporter (SLC6A4) Promoter Polymorphism. Psychiatric Genetics, In Press

Veenstra-Vander Weele, J., Qaadir, A. Palmer, A.A., Cook, E.H., de Wit, H. Association between the Casein Kinase 1 Epsilon gene region and subjective response to D-amphetamine. Neuropsychopharmacology, In Press.

Yonan, A.L., Chacon, I., Cheng, R., Cayanis, E., Ross, B.M., Cox, N.J., Palmer, A.A., Gilliam, T.C. An Examination of the Serotonin Transporter (SLC6A4) in Autistic and Control Populations. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, Submitted.

Palmer, A.A., Lessov-Schlaggar, C.N., Ponder, C. A., McKinnon, C. S., Phillips, T. J. Sensitivity to the locomotor stimulant effects of ethanol and allopregnanolone: a QTL study of common genetic influence. Genes, Brain and Behavior, Submitted.

Last updated 07/20/06