IMS Magazine - Summer 2012 edition in PDF format - Institute of ...

FEATURE
Psychiatric Pharmacogenetics
Maximizing Benefits While Minimizing Side Effects
By Zeynep Yilmaz, PhD candidate
lizing medications, essentially coining the
term “pharmacogenetics.” Prof. Kalow and
I trained students in my laboratory, and before
he passed away, he saw the fruits of these
labours with the delivery of genetic tests for
characterizing drug metabolism. Another
Toronto researcher, Dr. Victor Ling, discovered
the role of drug transporter proteins,
for which there are now DNA-based tests to
determine their variation across individuals.
Given this powerful history in pharmacogenetics
at the University of Toronto, I was
inspired to carry the science forward using
the developments in the human genome and
genetic testing technology.
James L. Kennedy, MD, MSc, FRCP(C)
Dr. James L. Kennedy is the Director
of the Neuroscience Research
Department at the Centre for Addiction
and Mental Health and the Co-Director
of the Brain and Therapeutics Division in
the Department of Psychiatry, University of
Toronto. Dr. Kennedy has an extensive, and
unique combination of training in psychiatry,
genetics, and neuroscience. As a professor
and full-member of IMS, he has supervised
well over a hundred trainees, including
undergraduate and graduate students, postdoctoral
fellows, and visiting scientists.
What is pharmacogenetics, and why is it
important to study?
Pharmacogenetics is the science of linking a
person’s DNA sequence with their response
to medication. Because DNA provides its
own unique blueprint of the body, we can
make specific predictions as to the right drug
and its correct dosage for a particular patient.
We hope to prevent patients from continuing
for weeks on ineffective medication and
then having to switch to another medication,
going through the entire disappointing sequence
of non-response. We need to move
beyond trial-and-error prescription of medications.
With pharmacogenetics, we can help
predict which patients will not respond to a
particular medication, and also predict the
best choice of medication on the basis of
their genotype and psychiatric condition.
How did you become interested in pharmacogenetics?
I became interested in pharmacogenetics
when I witnessed many patients suffer while
receiving the standard textbook dose of an
antidepressant or antipsychotic medication. I
saw the answer was in the power of new DNA
technology for testing patients to determine
their combination of genetic variants and
whether a given patient metabolized the
medication quickly or slowly. I had also read
seminal papers by Prof. Werner Kalow from
his work here at the University of Toronto in
the late-1950s and 1960s. He was the first to
point out that people were genetically predisposed
to having different rates for metabo-
What are some of the clinical applications
of pharmacogenetics in psychiatry?
We have a number of patented genetic discoveries
making their way into the clinic, including
a test using dopamine system genes
to predict risk for tardive dyskinesia (uncontrolled
muscle movements) as a result of
prolonged use of antipsychotic medications.
We also have a genetic test that identifies depressed
patients who are at risk for developing
mania as a result of their antidepressant
treatment. We have just published an important
paper showing the role of the melanocortin
4 receptor (MC4R) gene in determining
the risk for antipsychotic-induced weight
gain. The newer antipsychotic medications
have the side effect of substantial weight gain;
some patients will gain more than 100 lb during
one year of treatment and often go on to
develop diabetes and heart disease. After the
initial finding of this gene’s effect in the first
sample, we replicated the exact same result in
three independent samples.
It is now possible for the physician to see
a patient in the morning, for the patient to
have a quick sampling of their saliva using a
swab, and this sample to be shipped off to a
specialized lab where the genotyping of the
relevant genetic variants for common medications
can be done overnight. The results
are emailed to the physician the next day, and
the physician writes a prescription on the ba
Photos by Yekta Dowlati.
17 | IMS MAGAZINE SUMMER 2012 GENOMIC MEDICINE