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The overriding goal of the Transdisciplinary
Imaging Genetics Center, an exploratory center, is to enhance our
understanding of brain function in health and disease, through
facilitation of development of a new discipline, referred to as Imaging
Genetics. The Center does this by assembling an interdisciplinary team
of experts from U.C. Irvine and the University of Toronto with experience
in genomics, imaging analysis, statistical methods, and complementary
areas viewed as key to this goal. These experts, complemented by the
Center's consultants and External Advisory Board, have developed novel
methods in their respective fields. The major focus of this project
is to develop methods for combining imaging and genomics.
It is clear that mental illness involves brain
dysfunction that can be visualized with advanced brain imaging
techniques. Mental illness as well as normal brain function also has
a hereditary component; therefore, it is essential that the genes
related to aspects of brain development, mental function and dysfunction,
be considered. The integration of the imaging data with the rich genetic
data resulting from the human genome project will enhance our
understanding of brain function and mental illness. The value of this
integration is illustrated in our initial studies that demonstrated an
association between brain metabolism, clinical response and DRD1 alleles
(Potkin at al, 2003), and between brain metabolism, risk of tardive
dyskinesia, a motor side-effect on antipsychotic treatment, and DRD3
alleles (Potkin et al 2003b, Basile et al, 2002).
Figure: Combined Imaging and Genetics Studies. The
image on the left represents the regional glucose metabolic changes
following clozapine for schizophrenic subjects with the 2,2 alleles
for the DRD1 gene. The middle image represents the same changes for
the schizophrenic subjects with the 1,2 alleles DRD1. Following
clozapine treatment, the 2,2 allele subjects respond clinically and
alter their brain metabolic response, while 1,2 subjects do not respond
clinically or metabolically to clozapine. The image on the right
represents the difference between brain metabolic response in subjects
homozygous for the DRD3 glycine allele and those with glycine9serine
or serine9serine alleles. The glycine9glycine DRD3 allele subjects who
are at increased risk for tardive dyskinesia increase their ventral
striatal metabolic response following haloperidol, while the other subjects
(without the glycine9glycine allele) do not.
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