Kent E. Hutchison
One very important aspect to our research is
the notion that having well defined phenotypes that are proximal
to the underlying biological mechanisms is critical to the success
of efforts designed to uncover genetic variation that contributes
to these phenotypes. In other words, a rudimentary phenotype like
whether a person smokes cigarettes (or not) is unlikely to be useful
in a genetic study because of the sheer number of factors that may
influence that phenotype. Much of our research to date has focused
on refining the phenotype such that a given phenotype will be useful
in a genetic study. To date, we have focused on acute responses
to alcohol, tobacco, and marijuana, publishing papers on pharmacological
and genetic factors that influence these phenotypes. While acute
responses to cues or the drugs themselves are useful phenotypes,
we are currently working to develop phenotypes that are even more
proximal to the neurobiology of addiction. Working with the MIND
Institute, we have taken our laboratory based phenotypes to a neuroimaging
environment and are integrating this approach with our recent efforts
at identifying genetic variation that influences gene expression
in post-mortem tissue samples taken from brain regions that are
critical to the neurobiology of addiction. Thus, the genetic approach
should yield valuable information about genetic variation that alters
gene expression in critical brain areas. The neuroimaging approach
will allow us to examine whether this genetic variation also has
an impact in vivo on brain activation in response to a drug or drug-related
cues.
Hutchison, K.E., Allen, D., Jepson, C., Lerman, C.,
Benowitz, N., Stitzel, J., Bryan, A., McGeary, J., & Haughey,
H.M. (in press). CHRNA4 and Tobacco Dependence: From Gene Regulation
to Treatment Outcome. Archives of General Psychiatry.
Ray, L.A. & Hutchison, K.E. (in press). A Double-Blind
Placebo-Controlled Study of the Effects of Naltrexone on Alcohol
Sensitivity and Genetic Moderators of Medication Response. Archives
of General Psychiatry.
Hutchison, K.E., Ray, L., Sandman, E., Rutter, M-C,
Peters, A., Davidson, D., & Swift, R. (2006). The Effect of
Olanzapine on Craving and Alcohol Consumption, Neuropsychopharmacology,
31(6), 1310-1317.
Hutchison, K.E., Stallings, M., McGeary, J.M., &
Bryan, A. (2004). Population stratification in the case-control
design: Fatal threat or red herring? Psychological Bulletin, 130,
66-79.
Hutchison, K.E., Wooden, A., Swift, R., McGeary, J.,
Adler, L., Paris, L. (2003). Olanzapine reduces craving for alcohol:
A DRD4 VNTR polymorphism by pharmacotherapy interaction. Neuropsychopharmacology,
28, 1882-1888.