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

FEATURE
sis of the patient’s genetic profile. There is little
delay in starting treatment, and the choice
of medication is precise and targeted to avoid
side effects and achieve the best response.
On which psychiatric disorders are you
conducting pharmacogenetic studies?
I expect that pharmacogenetic information
will apply to virtually every psychiatric
disorder. Over the 20 years that I have
been doing research here at CAMH/UofT,
I have overseen the collection of more than
24,000 DNA samples for disorders including
schizophrenia, bipolar disorder, obsessive
compulsive disorder, attention-deficit/hyperactivity
disorder, addictions, eating disorders,
suicidality in teenagers treated with
antidepressants, as well as severe depression
in young children. Unfortunately, not all of
these patients have been characterized in
terms of medication response. These studies
are difficult because they require a patient to
be followed over an extended period of time.
Nonetheless, we have several thousand DNA
samples from psychiatric patients with drug
response and side effect information – one of
the largest collections in the world.
How do you predict the future of pharmacogenetics?
As we move into the future, I see many benefits
arising from pharmacogenetic testing
in the population. It is easy to imagine the
substantial healthcare savings when we can
prevent non-response or debilitating side effects
from medication treatment. If patients
are prescribed the right drug from the start,
they should have fewer doctor visits and stay
compliant with their medication. Currently,
under our large pharmacogenetic initiative
funded by the Ministry of Economic
Development and Innovation to test 20,000
patients, Ontario stands to be the leader, as
the largest single geographic region offering
pharmacogenetic testing in the world. Personalized
medicine with pharmacogenetics
is estimated to save Ontario at least $88
million in health care costs over the next 5
years. Pharmacogenetics is a very exciting
area benefiting from rapid increases in DNAbased
information, and computer-based algorithms
combining information from multiple
gene variants together to create more
powerful methods to define an individual’s
tailor-made treatment.
One of our recent projects is an innovative
treatment for anorexia nervosa. We believe
that one of the medications that has a calming
effect in schizophrenia patients, but causes
weight gain, may be helpful in anorexia nervosa
by reducing anxiety associated with eating.
It will be interesting to see if MC4R gene
variation can predict those individuals that,
in this case, gain weight in a helpful way. The
fact that MC4R is expressed in the appetite
centre of the brain may help demonstrate its
value in predicting the patients that would
get the most benefit from this medication.
Pick Your Brain...
A column by Aaron Kucyi
Illustration by Andreea Margineanu.
The human brain is the most complicated feature
of the human body, and it presents many unique
challenges to genomics research. The best, and
perhaps only, effective approach to understanding
the genetics of brain structure is to combine data
from multiple research sites to conduct studies
with very large and diverse population samples.
In the largest MRI study of the brain to date, researchers
from several sites around the world
reported new links between specific gene variants
and total brain volume, intracranial volume,
and hippocampal volume. The study was
possible because investigators in North America,
Europe, and Australia combined brain imaging and
genetics data from over 21,000 human subjects in a
“crowdsourcing” project. Some findings—such as
that of a strong link between hippocampal volume
and the rs7294919 variant—were not in agreement
with previous smaller studies. Because hippocampal
and other brain volume measures have relevance to
neuropsychiatric disorders, including Alzheimer’s disease,
schizophrenia, and depression, the new findings
may lead to personalized genomic approaches
to therapy.
The study highlights the usefulness of, and need
for, further large-scale multinational collaborations
in the field of brain imaging genetics. The
200+ authors of the study caution that their work is
just a preliminary step and that the findings need
to be confirmed and extended before this type of
work can lead to targeted treatments for neuropsychiatric
disorders.
Reference:
Stein et al. Identification of common variants associated with human
hippocampal and intracranial volumes. Nat Genet. 2012;44(5):552-561.
IMS MAGAZINE SUMMER 2012 GENOMIC MEDICINE | 18