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breakthrough
WINTER 2015/16
Genetics
and the
environment
Detecting risk in
childhood
Discoveries
in brain science
New views on mental illness
The end of side effects:
How genetic testing improves treatment
also inside…
CAMH’s
Treating
imaging tools depression in
Transforming how the
youth without
world sees mental illness
medications
The brain’s role in depression
Alzheimer's disease:
New approach to prevention
B R E A K T H R O U G H C A M PA I G N
The future of mental health care is here.
The Campbell Family Mental Health Research Institute at CAMH is Canada’s
leading institute dedicated to translating new scientific discoveries into
better mental health care.
We are committed to applying our expertise in brain imaging, genetics, and molecular
science to revolutionize treatment and improve lives.
Thanks to the generous support of Linda Campbell, Susan Grange, Gaye Farncombe, and
their families, the Campbell Family Mental Health Research Institute is transforming the lives
of people living with mental illness.
The next breakthroughs in mental health are happening at CAMH.
www.supportcamh.ca/breakthrough
contents
The
Campbell
Institute
paves the way
for a brighter
future
WINTER
2015/16
12
4 Nature and nurture
How multiple factors in
childhood may affect the brain
in adulthood
7 Big data
Bioinformatics mines and
analyzes genetic information
to reveal the cause of illness
First in show
CAMH research milestones
5 Youth psychosis
How CAMH’s Campbell
Institute is pinpointing risks
before illnesses can develop
Radiotracers
Visualizing brain changes
6 Emerging discoveries
Understanding the complex
biology behind mental illness
8 Personalized medicine
Zeroing in on customized
treatment, patient by patient
11 Medication
development
Hope for alleviating the
harmful side effects of drugs
12 Fahad’s journey
How CAMH’s non-invasive
brain stimulation therapy
helped one patient get his life
back on track
ON THE COVER:
CAMH’s imaging technology provides new insight into the living brain and mental illness.
One in three Canadians
One
in three
during
their lifetime
will experience
during
theirCanadians
lifetime will
experience
a brain-related
a
brain-related
such asschizophrenia,
depression, schizophrenia,
illness,
such asillness,
depression,
addiction or
addiction or Alzheimer’s disease. And while some are
Alzheimer’s disease. And while some are successfully
successfully treated, too many are not. Current treatments
treated, too many are not. Current treatments don’t
don’t fully address the complex causes of these illnesses.
fully address the complex causes of these illnesses.
In 2011, recognizing the urgent need for innovation
In 2011, recognizing the urgent need for innovation
in mental illness research, the Campbell family made a
in
mental illness research, the Campbell family made
landmark donation to the Centre for Addiction and
a
landmark
donation
thegift
Centre
for Addiction
Mental Health
(CAMH).to
This
launched
the Campbell
and Mental
Health
gift launched
the
Family
Mental
Health(CAMH).
ResearchThis
Institute,
where today
Campbell
Family
Mental Health
Researchas
Institute,
there is a sense
of excitement
and optimism,
where
today there
is a sense
excitement
and
groundbreaking
discoveries
areof
leading
to a better
optimism, as groundbreaking
understanding
of mental illness. discoveries are leading to
a Consider
better understanding
mental
illness.
depression. It’softhe
leading
cause of
Consider
depression.
It’s the
leading cause
of half
disability
globally,
but current
treatments
help only
disability
globally,
but current
treatments
help we’ve
only
of
those with
the illness.
At the Campbell
Institute,
developed
a chemical
probe,
which
showed,Institute,
for
half of those
with thebrain
illness.
At the
Campbell
the
first
time, evidence
of inflammation
in the
brains of
we’ve
developed
a chemical
brain probe,
which
those
withfor
depression.
showed,
the first time, evidence of inflammation
of this discovery could lead to
inOur
thecontinued
brains of exploration
those with depression.
anOur
entirely
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continued
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Theto
questions
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lead
an entirely
new
way of treating
depression.
magazine,
are provocative
and paradigm-shifting.
Can
The questions
we’re investigating,
highlighted
in we
prevent
the development
of mental
illnesses?
Can treating
this magazine,
are provocative
and
paradigm-shifting.
depression delay the onset of Alzheimer’s disease? Will
Can we prevent the development of mental illnesses?
novel brain stimulation and cognitive therapies enhance
Can treating depression delay the onset of Alzheimer’s
treatment for many brain-based illnesses?
disease? Will novel brain stimulation and cognitive
The Campbell Institute – which brings together the
therapies enhance treatment for many brain-based
latest brain science technologies and expertise in genetics,
illnesses?
molecular science and brain imaging – is successfully
The Campbell
Institutein– the
which
brings
together
translating
breakthroughs
lab into
new
options the
latest
brain
science
technologies
and expertise
in
for patient
care.
With this
pace of progress,
we can offer
genetics,
molecular
science
and
brain
imaging
–
Canadians hope for the future and stop mental illnessisfrom
successfully
translating breakthroughs in the lab into
destroying
lives.
new options for patient care. With this pace of progress,
we
canG.
offer
Canadians
hope FRCPC
for the future and stop
Bruce
Pollock,
MD, PhD,
mental
illness
from
destroying
lives.
Vice-President, Research, CAMH
Director,
Mental
Health Research Institute
Bruce G.Campbell
Pollock,Family
MD, PhD,
FRCPC
Vice-President, Research, CAMH
Director, Campbell Family Mental Health Research Institute
11
EDITOR
EDITOR
Elizabeth Holland
Breakthrough magazine
is designed and produced
by The Globe and Mail
Custom Content Group
on behalf of CAMH.
Printing and pre-press by
Metagraphic Network
©2015 Globe Edge
ART DIRECTOR
DIRECTOR
Kamille Chin
CONTRIBUTORS
CONTRIBUTORS
Thomas Bollmann,
Brenda Bouw, Dali Castro,
Mary Gooderham,
Kevin Hand,
Hand, Wallace
Kevin
Wallace
Immen, June
June Rogers,
Rogers,
Immen,
Roger Yip
Roger Yip
PUBLISHERS
PUBLISHERS
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Rowe,
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Meek,
Anita
Kate Richards
Kate Richards
SPECIAL THANKS
toCAMH
CAMH staff,
SPECIAL
THANKSto
staff, clinicians, researchers and
clinicians,
researchers
andstories
patients who
shared their
patients
who shared their stories
in this publication.
in this publication.
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breakthrough | CAMH
3
Canada’s
leader
New research
reveals how
genes and
early childhood
experiences can
increase the risk
for mental illness.
Nature and nurture
Early findings
findings of landmark study show multiple factors in
childhood can lead to mental illness in adulthood
Dr. Robert Levitan of CAMH’s Campbell
Family Mental Health Research
Institute has spent his career seeking
to better understand the origins of his
adult patients’ illnesses and the oftencommon link between mood disorders
and overeating and obesity.
Through his work with a landmark
Canadian study, Dr. Levitan is gaining
new insight into the earliest origins
of illness and is encouraged by new
findings showing how the
research findings
exchange between both genetic and
environmental factors increase risk.
“The whole dance of nature and
nurture is more multidirectional than
one might have thought,” he says.
Dr. Levitan is part of the Maternal
Adversity, Vulnerability and
Neurodevelopment (MAVAN) study,
which is investigating the interplay
between genes and environment in
nearly 550 children and their mothers –
tracking children’s development over the
course of several years.
Along with his Canadian colleagues,
Dr. Levitan is gathering compelling
evidence that early childhood
experiences, mother-infant interactions
and genetic susceptibility increase the
risk for mental illness later in life.
“A lot of research to date is in
understanding the advanced stages of
diseases,” he explains. “With the MAVAN
4 breakthrough | CAMH
study, we’re going back to understanding
how it all started.”
The MAVAN project is a novel example
of how researchers are combining
expertise in a range of specialties
including developmental neurobiology,
genetics, attachment theory, and
nutrition, to unlock the complexity of
psychiatric problems.
By investigating weight regulation
and eating behaviours in childhood,
Dr. Levitan can better understand the
link between depression and obesity
in adults. His recent research,
research looked
looked
at maternal sensitivity – how attuned a
mother is to her child – and found that
girls who experienced low maternal
sensitivity at six months of age had
higher body mass index (BMI) scores
at 48 months.
In a follow-up study, he also found
this link occurred only in girls with a
particular variation of a gene called the
dopamine-4 receptor gene, or DRD4.
“This suggests that it’s the combination
of a certain gene and a certain
environment that may lead to obesity,
rather than either alone,” he says.
“The positive message in this is that
we are really getting to understand the
human brain as well as vulnerability and
resilience, which will help us develop
new treatments and approaches,” says
Dr. Levitan. “It’s a message of hope.”
—Brenda Bouw
CAMH’s Campbell
CAMH’s
Camp
a pbe
bell
Family
Mental
Health
F
a ili y M
am
e tal H
en
ealth
ea
Research
R
e ea h Institute
esearc
Institute
excels
e
xce
els iin
n genetics,
ge etics,
gene
brain
b
ra
ain imaging
imag
aging
g and
a d
an
molecular
mo
olec
e ular
a science,
science
e e,
and
a
an
d ffeatures:
eatures
ea
e :
the Research Imaging Centre,
one of the few brain-imaging
facilities in the world fully
dedicated to mental illness
research;
the Temerty Centre for
Therapeutic Brain Intervention,
home to one of the world’s
most talented concentrations of
specialists exploring non-invasive
brain-stimulation treatments for
mental illness;
the Tanenbaum Centre for
Pharmacogenetics, the only
centre in Canada to partner with
family practices on genetic testing
for personalized prescribing of
psychiatric medications;
the first
first positron emission
tomography (PET) imaging studies
of dopamine changes in the
brains of young people at risk of
schizophrenia;
one of the largest collections of
DNA in Canada, with over 25,000
samples donated by patients with
mental illness;
a specialized radiochemistry
program that has developed half
of all the chemical brain probes
currently used to investigate
mental illness in brain imaging
research around the world;
the only Canadian site to
contribute to the world’s largest
mega-analysis of genetic data
focusing on identifying new
genetic targets for schizophrenia.
Dr. Romina
Mizrahi seeks
new ways
to prevent
schizophrenia
in young
people.
Ahead of
the game
Predictive testing for
early warning signs can
prevent a lifetime of illness
for young people
Early intervention may be the
key to preventing schizophrenia.
Researchers at CAMH’s Campbell
Institute, like Dr. Romina Mizrahi,
are exploring innovative approaches
to help those at highest risk before
they develop symptoms.
The warning signs of psychosis usually
occur in young people in their late
teens and early
20s and, if not
identified and
identified
treated early,
can lead to
a lifetime of
illness, such as
schizophrenia.
Prevention
is the future
of mental health, notes Dr. Mizrahi,
director of the Focus on Youth
Psychosis Prevention Clinic, one
of the few research-based clinics
worldwide treating youth at high
risk of developing schizophrenia.
“The longer an illness is left
untreated,” she says, “the greater the
disruptions to the person’s ability to
study, work, make friends and interact
comfortably with others.”
Powered by the Campbell Institute’s
Research Imaging Centre, Dr. Mizrahi
has achieved groundbreaking results
that offer a better understanding of
schizophrenia.
Incorporating PET scan brain imaging
with her clinical work, she has made
some important discoveries related
to specific
specific brain changes in this
population. For example, she discovered
that these young people release
abnormally high amounts of dopamine
in their brains when under stress.
“One of the important triggers for
psychosis is major stress,” Dr. Mizrahi
explains. “We have found that cortisol – a
stress hormone that can be measured in
a saliva test – is a very good predictor of
psychiatric risk down the road.”
Part of her work includes stressreducing group therapy sessions that
help youth at risk develop resiliency. Her
work is also looking at substance use,
particularly marijuana, and its potential
role for increasing risk for psychosis.
Dr. Mizrahi and her team use multiple
approaches to predict who will develop
psychosis, including genetic testing,
scans to evaluate dopamine chemistry or
inflammation, and neuropsychological
inflammation,
testing.
An extremely encouraging discovery
from Dr. Mizrahi’s research is that for
the majority of youth, early symptoms of
psychosis, such as paranoia or hearing
imaginary voices, don’t necessarily lead
to schizophrenia later in life.
“What we see in the clinic is that
one-third of high-risk people develop a
chronic illness and while another onethird will continue to have occasional
episodes, this will not develop into a
severe mental illness,” she says. And in
final third, the symptoms go away on
a final
their own.
five years
“We are now aiming within five
to not only be 100 per cent predictive
of who is at risk of chronic illness, but
also have the means in place to prevent
psychosis in young people,” Dr. Mizrahi
says. “That’s what I hope for and I am
dent, because we are getting
very confi
confident,
so close.”
—Wallace Immen
Picture
this
PHOTOGRAHY BY THOMAS BOLLMANN
Radiotracers
R
adi
diotrace
a ers developed
deevelope
d
oped
d at
at CAMH’s
CAMH’
A
s Campbell
Camp
a pbe
bell Institute
Institute help
help
rresearchers
e earchers around
esea
around the
the world
world
d unlock
unloc
o k the
the mysteries
mysteries
e of
of the
the brain
brain
One of the most revolutionary advances in
psychiatry has been the ability to visualize
molecular changes in the living brain. Today,
researchers have a remarkable tool – the radiotracer
– that enables them to not only investigate the
cause of symptoms, but also to develop new
treatments.
Radiotracers are radioactive isotopes designed to
connect with specific
specific chemical targets in the brain
– neurotransmitters – that can be viewed using
positron emission tomography (PET) imaging.
CAMH’s Campbell Institute specializes in this
technology and invented half of all the radiotracers
used in brain-imaging research around the world.
“The images that we look at are a chemical map of
what’s happening in the brain,” explains Dr. Sylvain
Houle, founding director of the Campbell Institute’s
Research Imaging Centre at CAMH. “This is how we
know what’s going on in the brain. And it allows for
more precise research.”
The technology is being used to study changes in
brain chemistry in a variety of illnesses,
illnesses including
including
depression, schizophrenia, addiction and even
Alzheimer’s disease. A new radiotracer developed at
the Campbell Institute recently led to an important
breakthrough revealing brain infl
inflammation
ammation as an
underlying factor in depression.
“Our strength is to have the ability to make these
special molecules, but we also have the people
with the knowledge and the expertise to apply it to
mental illnesses,” says Dr. Houle.
—Brenda —B.B.
Bouw
breakthrough | CAMH
5
GAM E- CHANGERS
Emerging discoveries
CAMH’s Campbell Institute’s leading-edge research explains
the biology behind depression
BY BRENDA BOUW
Some of the most groundbreaking
research on depression being
conducted today doesn’t involve
a specifi
specificc treatment or drug, but
instead the discovery that there are
multiple changes in the brain that
can trigger this mental illness.
Thanks to leading-edge studies
conducted by Dr. Jeffrey Meyer,
senior scientist at CAMH’s Campbell
Institute, researchers are discovering
a remarkable variety of biological
causes behind depression.
The trailblazing research, which
shows that depression isn’t a “onesize-fi
size-fits-all”
ts-all” illness, is expected to
have a profound impact on how
doctors will diagnose and treat
mental illness.
“Our understanding about
depression is evolving,” says Dr.
Meyer, who has spent most of his
career studying mood disorders.
The science has changed
dramatically from past theories that
depression was caused solely by low
serotonin in the brain, he says.
“There isn’t one way a person gets
clinical depression biologically; there
6 breakthrough | CAMH
are probably multiple ways,” he
explains.
Dr. Meyer’s research led to several
new discoveries on what causes
depression using positron emission
tomography (PET) brain imaging and
chemical probes created at CAMH’s
Campbell Institute.
These sophisticated brain-imaging
techniques have revealed that
depression can vary significantly
significantly
depending on factors such as the age
and sex of the patient.
His two broad areas of discovery
include MAO-A (an enzyme
that breaks down chemicals like
serotonin and dopamine) and brain
inflammation.
inflammation.
He was the first
first to show that in
major depression, the MAO-A level
was significantly
significantly higher in every
brain region. Higher MAO-A levels
lead to increased breakdown of
key mood-regulating chemicals
like serotonin.
Dr. Meyer has shown that MAO-A
was increased in people with
seasonal affective disorder, in women
shortly after giving birth and in
perimenopause,
as well as in
people who
recently quit
smoking.
In his work
on postpartum
depression – the
most common
complication in
childbearing that affects 13 per cent
of women who give birth – Dr. Meyer
found increased MAO-A levels.
To replace the mood-enhancing
chemicals being stripped away
by high levels of MAO-A, he came
up with a specially formulated
dietary supplement as a potential
treatment. It is currently being
tested with new mothers.
The postpartum depression
study follows his research on the
first-time
high rates of fi
rst-time depression
among women experiencing
perimenopause.
first
It was the fi
rst time that a
biological change in the brain has
identified
been identifi
ed in perimenopause
and may explain the onset of
first-time
fi
rst-time depression in women
of this age group.
first,
In a new world fi
rst, Dr. Meyer
recently proved the link between
inflammation
brain infl
ammation and depression.
His study showed that brain
inflammation
infl
ammation was 30 per cent higher
in patients experiencing clinical
depression than in people with no
depression.
The discovery could lead to an
entirely new approach to treatment.
Many of the fi
findings
ndings in Dr. Meyer’s
more than a dozen ongoing studies
on depression are being applied
in clinical trials, and treatments
beyond traditional antidepressant
medications could soon be in
widespread use.
PHOTOGRAHY BY ROGER YIP
Dr. Jeffrey Meyer,
senior scientist at
CAMH’s Campbell
Institute, is proving
that depression isn’t
a “one-size-fits-all”
“one-size-fits-all”
illness.
RESEARCH REV OLUT I ON
Computing
genes
Big data,
huge impact
Leading-edge technologies
are opening new frontiers
of discovery
PHOTOGRAHY BY ROGER YIP
BY MARY GOODERHAM
Serious mental illnesses require
complex investigative tools. For Dr.
Etienne Sibille, that means bridging
technology and biology, using
bioinformatics, or “big data,” to discover
the molecular mechanisms behind
psychiatric illnesses.
Bioinformatics – collecting
and analyzing complex biological
data – is the new frontier in
mental-health research.
“We are mining data, understanding
it and learning lessons out of it,” says
Dr. Sibille, the inaugural holder of
CAMH’s Campbell Family Chair in
Clinical Neuroscience. Major advances
in molecular biology and genetics, as
well as technologies ranging from laser
microscopes and brain imaging to
super-computers, allow researchers to
dramatically expand the scope of their
research, he explains. “You get a really
broad picture.”
A molecular neuroscientist, Dr. Sibille
focuses on the cellular changes in the
brain associated with depression as
well as normal aging. In fact, his lab
Dr. Etienne
Sibille, Campbell
has demonstrated that
Family Chair
molecular mechanisms
in Clinical
involved in the aging of the
Neuroscience,
says the institute
brain overlap with – and
is “a hub of
may in fact promote –
ingenuity.”
neuropsychiatric diseases.
At CAMH’s Campbell
Institute, which Dr.
Sibille calls a “hub of
ingenuity” and an incubator for new
ideas, researchers are at the forefront of
applying bioinformatics to brain science.
One such researcher is Dr. Aristotle
Voineskos, head of the Kimel Family
Translational Imaging-Genetics
Laboratory. He leads an international
research project focusing on the most
challenging aspects of schizophrenia.
The ambitious fi
five-year
ve-year study, which
includes research teams in New York
and Maryland, combines brain scans
and genetic information to identify
and map genes associated with social
impairments in schizophrenia.
There are no treatments for these
problems, which can include social
withdrawal, lack of motivation and
an inability to complete simple daily
tasks, and can be more disabling than
hallucinations and agitation.
Given that the genetic code has some
three billion variants, the volume of data
will be astronomical. “There are many
millions of variables on each person,”
says Dr. Voineskos, CAMH’s Koerner New
Scientist, noting that bioinformatics will
allow his team to extract meaning from
these large datasets faster than has ever
been possible before.
Researchers have
long believed that a
predisposition to mental
illness is heritable: it’s
encoded in our DNA.
However, we know that
identical twins with the same
genetic makeup do not
necessarily both develop a
particular illness, such as
schizophrenia.
In fact, if a twin has a sibling
with schizophrenia, the other
twin has only a 50 per cent
chanceof
ofdeveloping
developing
chance
schizophrenia, not 100 per
cent. Why?
The answer may be revealed
by a relatively new science
known as epigenetics, the
study of how genes function in
the body.
Epigenetics is revealing that
environmental factors such
as stress, diet or trauma can
affect how otherwise normal
genes dysfunction, explains
Dr. Art Petronis, head of the
Campbell Institute’s Krembil
Family Epigenetics Laboratory.
A recent study by Dr.
Petronis of 100 sets of
identical twins — each set
with one twin with depression
and the other twin without
— looked for molecules that
attach to DNA and affect
various gene activities that
can explain the differences.
Using bioinformatics
techniques, Dr. Petronis has
been able to identify the
epigenetic differences between
each twin, which may explain
why one has depression and
the other doesn’t.
findings are part of
These findings
a larger study looking at new
strategies to map epigenetic
changes in depression.
“If we can discover what the
initial mechanisms in a disease
are, then we can be much
efficient in treatments,”
more efficient
says Dr. Petronis.
—Wallace Immen
breakthrough | CAMH
7
Dr. Jim Kennedy, head
of the Campbell Institute’s
Tanenbaum Centre for
Pharmacogenetics:
“Personalized medicine
will be a life-changer.”
8 breakthrough | CAMH
PHOTOGRAHY BY NAME NAME
IN BRIEF / TAG
PERSONALIZED M E DI CAT I ONS
Tailor-made
treatment
Genetic-testing tools make medications more effective for patients
PHOTOGRAHY BY THIOMAS BOLLMANN
BY JUNE ROGERS
KRISTIN MACPHERSON GREW UP IN
INCARING,
A
A CARING,
CLOSE-KNIT
CLOSE-KNIT
FAMILY.
FAMILY.
Her
father
was was
a highly
respected
cardiologist
Her father
a highly
respected
and
internist,
herinternist,
mother aher
journalist.
cardiologist
and
mother a
At
Branksome
Hall, a private
for
journalist.
At Branksome
Hall,school
a private
girls
in for
Toronto,
excelled
inexcelled
art and
school
girls inshe
Toronto,
she
sports,
especially
cross-country
skiing.
in art and
sports, especially
crossShe
reached
theShe
topreached
of her class
in her
country
skiing.
the top
of
last
year of
school.
her class
in high
her last
year of high school.
But by the mid-1980s, when Kristin
turned 18, her life changed dramatically.
“I started having severe crying spells,”
she says. “I wasn’t sleeping or eating.”
She also experienced insomnia, rapid
speech and restlessness. Cruel voices
crept into her head, taunting her with
belittling messages. Increasingly losing
touch with reality, she alternated
between believing she was an angel
and seeing the devil.
Kristin’s sister, Bryn, was also deeply
affected as she watched her sister sink
into a mental illness that required longterm psychiatric hospital stays and drove
Kristin to attempt suicide – twice. Says
Bryn: “I was devastated to see my little
sister, who was so spirited and creative,
go through so much.”
It took until 1993, when Kristin
became a patient of psychiatrist
Jim Kennedy, head of the Campbell
Institute’s Tanenbaum Centre for
Pharmacogenetics at CAMH, before she
began her slow climb to health.
Dr. Kennedy and his team have
harnessed the promise of using genetic
tests to match patients with the most
effective treatments. This innovative area
of research is known as personalized, or
genomic, medicine.
Says Dr. Kennedy: “It is estimated
that personalized medicine will be a
life-changer for one in five
five Canadians,
young and old, who experience mental
illness – anything from chronic anxiety,
obsessive-compulsive disorder and
depression to bipolar disorder and
schizophrenia.”
Before she arrived at CAMH, Kristin,
now 47, was treated at other leading
Canadian and U.S. hospitals. She
was diagnosed with bipolar disorder,
then schizoaffective disorder. She was
prescribed clozapine, an anti-psychotic
medication. At the recommended
dose, Kristin found little relief from
her symptoms.
By the time she became Dr. Kennedy’s
patient, her prognosis was dire. She
still had hallucinations and had also
developed Type 2 diabetes.
“We put her on another anti-psychotic,
which turned out to be disastrous,”
says Dr. Kennedy. “I was treating
Kristin by the book, but it was
frustrating because we couldn’t
find the right medication for her.”
find
On a hunch, Dr. Kennedy began testing
her DNA to look for genetic markers
that might unravel the conundrum. The
tests revealed what he suspected: that
manufacturer-recommended dosages
needed refinement.
refinement.
“We found out that Kristin is a rapid
metabolizer and can safely tolerate
higher-than-textbook dosages
of clozapine.”
Dr. Kennedy remembers the day when
Kristin came for an appointment and
told him that the voices had stopped. “I
knew then that we were finally
finally on the
right track,” he says.
Eventually, the genetic markers also
teased out which mood stabilizer and
antidepressant were best for her.
It was Kristin’s experience – and the
fact that up to 50 per cent of patients
do not respond well to psychiatric
medication – that compelled Dr.
Kennedy to relentlessly pursue the
Dr. Kennedy
and his team
have harnessed
the promise of
using genetic
tests to match
patients with the
most effective
treatments
promise of genomic medicine.
In 2012, Dr. Kennedy received a grant
from the Ontario Ministry of Research
and Innovation to launch Individualized
Medicine: Pharmacogenetic Assessment
and Clinical Treatment (IMPACT), the
largest study of its kind in the world.
The study analyzes cells from cheek
swabs and saliva to determine the
genetic markers that would best predict
effectiveness and prevent side effects
from 38 psychiatric medications. The
IMPACT study is using a genetic testing
tool known as GeneSight developed by
Assurex Health.
The test looks at serotonin’s transporter
transporter
and
receptorand
genes
receptor
to help
genes
predict
to which
help predict which
medications
will bemedications
effective, as well
will as
be effective,
how
the liveras
metabolizes
well as howdrugs.
the liver
metabolizes
If the liver processes
drugs.
a drug too
quickly,
If the liver
thenprocesses
it doesn’t aremain
drug too
in the
quickly,
body
long
then
enough
it doesn’t
to reach
remain
the in
brain
the
bodybe
and
long
effective.
enough
If to
it takes
reachlonger,
the brain
then
andmuch
too
be effective.
of the drug
If it takes
accumulates
longer, then
in
too body,
the
much causing
of the drug
sideaccumulates
effects such in
thenausea,
as
body, causing
dizziness,
sidelethargy
effects such
and
as nausea, libido.
decreased
dizziness, lethargy and
decreased
The IMPACT
libido.
study’s goal is to screen
breakthrough | CAMH
9
PERSONALIZED T RE AT M E NT
Dr. Jim Kennedy is overseeing
IMPACT, the largest study of its kind
in the world. It uses genetic testing
to predict the effectivness of 38
psychiatric medications.
GeneSight
20,000
The IMPACT
patients,study’s
ages 7goal
to 79,
is by
to 2018.
screenSo
far,
20,000
more
patients,
than 3,840
agespatients
7 to 79, by
have
2018.
taken
So
the
far, more
test. Since
than family
3,840 patients
doctors have
prescribe
taken
80
theper
test.
cent
Since
of psychiatric
family doctors
medications,
prescribe
the
80 per
testcent
has of
been
psychiatric
made available
medications,
to
more
the test
than
has1,100
beendoctors
made available
in Ontario.
to
About
more than
800 of
1,100
those
doctors
physicians
in Ontario.
surveyed
have
Aboutreported
800 of those
that 70
physicians
per cent surveyed
of their
patients
have reported
have experienced
that 70 per cent
signifi
of cant
their
improvement.
patients have experienced significant
improvement.
Partnering with CAMH’s Campbell
Institute
Partnering
on the
with
IMPACT
CAMH’s
study
Campbell
is Dr. Nick
Voudouris,
Institute onathe
family
IMPACT
doctor
study
at Thornhill
is Dr. Nick
Medical
Voudouris,
Centre.
a family doctor at Thornhill
Medical
“We’veCentre.
taken this personalized
medicine
“We’ve taken
approach
this personalized
to a suburban
clinical
medicine
setting,”
approach
saystoDr.
a suburban
Voudouris,
“where
clinical we
setting,”
see every
saysnationality
Dr. Voudouris,
and a
variety
“where of
wemental
see every
health
nationality
issues.” and a
variety
As part
ofof
mental
the IMPACT
health issues.”
study, Dr.
Voudouris
As part ofreceives
the IMPACT
a report
study,
from
Dr.Dr.
Kennedy’s
Voudouris team
receives
within
a report
two business
from Dr.
days
Kennedy’s
that indicates
team within
which
two
medications
business
are
daystailored
that indicates
to his patient’s
which medications
genotype
using
are tailored
stop-light
to his
indicators:
patient’s genotype
green for go,
yellow
using stop-light
for caution
indicators:
and red for
green
stop.
for go,
yellow
“It’s no
forlonger
caution
a cookie-cutter
and red for stop.
situation,”
“It’s no longer
says Dr.
a cookie-cutter
Voudouris. “We now
10 breakthrough | CAMH
know what says
situation,”
medications
Dr. Voudouris.
and dosages
“We now
will
know
be
effective.”
what medications and dosages will
beThe
effective.”
genetic testing reassures his
patients
The genetic
with scientifi
testing reassures
c proof that
his
patients
their
prescriptions
with scientifi
arectailored
proof that
to
their DNA,
prescriptions
he says. are tailored to
their
“I have
DNA,
one
hepatient
says. who saw the list
of“Ihis
have
‘green’
onemedications
patient who and
saw said
the list
of his
he
wanted
‘green’
tomedications
try all of them
and
until
said
he
he wanted
reached
a 10
toout
try all
of 10
of them
and felt
until
well
he
reachedsays
again,”
a 10Dr.
outVoudouris.
of 10 and felt well
again,”
“There’s
says
anDr.
artVoudouris.
in helping to convince
people
“There’s
to take
an art
medications
in helping to
in convince
the first
people he
place,”
to take
adds,medications
“and this genetic
in the first
place,” has
testing
he adds,
made“and
it much
this genetic
easier for
testing has
people
to accept.”
made it much easier for
people
Beingto
among
accept.”
the first patients to
benefi
Being
t from
among
Dr.the
Kennedy’s
first patients
genetic
to
testing,
benefit from
Kristin
Dr.can
Kennedy’s
confidently
genetic
say – and
her
testing,
sister,
Kristin
Bryn,can
agrees
confi
– dently
that her
say
life– has
and
changed
her sister,for
Bryn,
the agrees
better. – that her life has
changed
She sings
forinthe
a choir,
better.swims at the
YMCA
She sings
and has
in avolunteered
choir, swimsatatCAMH
the YMCA
for
andspeaking
has volunteered
engagements
for CAMH
for young
speaking
people
to young
and
people
law enforcement
and law enforcement
officers. “I
hope
officers.
that
“Ifuture
hope that
generations
future generations
with mental
illnesses
with mental
willillnesses
have it 10will
times
have
easier
it 10 than
Itimes
did.”easier than I did.”
Imagine a day when the medication
you take – whether it’s a painkiller,
cancer chemotherapy, cholesterol drug
or antidepressant – is prescribed based
on your unique genetic makeup.
That is Dr. Jim Kennedy’s long-term
hope. He believes that the results of
the IMPACT study he helped launch
will provide the impetus for Ontario’s
government – and hopefully many other
provincial jurisdictions – to adopt a DNA
screening test as a normal part of family
physician practice.
“Ideally, it will prevent a lot of human
suffering,” says Dr. Kennedy, “and
hopefully save a lot of health-care
dollars in the process.”
IMPACT uses a DNA test called
GeneSight to reveal each person’s
unique genotype and predict which
psychiatric medication would best treat
each patient’s mental illness.
The GeneSight technology, developed
by Assurex Health, a U.S. company,
incorporates genetic markers
discovered by CAMH’s Campbell
Institute. This industry partnership will
help translate the Institute’s discoveries
into better treatment for patients.
Genome-based, or personalized
medicine, is transforming health care as
we know it, says Dr. Kennedy.
“It is hoped that 80 per cent of
medications for all kinds of conditions
can be prescribed with better accuracy
and effectiveness using genetic testing,”
he says.
PHOTOGRAHY BY THOMAS BOLLMANN
DNA screening coming
soon to doctors’ offices
NEW APPROACH T O DRUG DE VE LOPM E NT
Proteins with purpose
Research investigates molecular actions linked to mental illnesses
BY MARY GOODERHAM
Dr. Fang Liu constantly hears
from patients and their
families “exasperated” with
the treatments for mental
illnesses like schizophrenia,
particularly the negative side
effects of drugs.
Today’s medications for
mental illness are variations
of drugs developed back in
the 1950s, Dr. Liu explains,
which produce limited
results and unwanted side
effects.
By better understanding
how cells communicate
with each other and cause
disorders of the brain and
nervous system, researchers
can develop more targeted
treatments.
Current drugs generally
target a particular receptor
or protein in the brain that
is not functioning properly,
such as the D2 receptor in
schizophrenia, and block all
of its functions or signalling
pathways.
The medication can treat
the unwanted symptom but
ends up producing other
effects, like the slow gait
common in people being
treated for schizophrenia.
Dr. Liu’s research
has produced a new
understanding of different
protein complexes linked
to illnesses. Based on this
understanding, it is possible
to “disrupt” the protein and
target one specific
specific treatment
pathway, while leaving others
to function normally.
Her work opens the door
to an entirely new approach
to treat brain-based
illnesses. She has developed
peptides that can disrupt the
molecular action that causes
symptoms.
For depression treatment,
she has even developed
an entirely new method to
administer the peptide. In
preliminary research, she is
exploring the effectiveness of
a nasal spray to deliver
Senior
scientist
Senior
Dr.
Fang Liu
scientist
is
Dr.studying
Fang Liu
how
cells
is studying
communicate
how cells
with
each
communicate
other,
with
with each
the
goal
of
other,
with
developing
the goal of
medications
developing
without
medications
adverse
without side
effects.
adverse side
effects.
the peptide to precise
areas
of the to
brain.
the peptide
precise
Her of
colleague,
areas
brain. Dr. Etienne
Sibille,
the Campbell
Family
Her colleague,
Dr. Etienne
Chair
Clinical
Neuroscience,
Sibille,inthe
Campbell
Family
is
studying
the connection
Chair
in Clinical
Neuroscience,
between
thethe
neurotransmitter
is studying
connection
GABA
and
depression,
and is
between
the
neurotransmitter
testing
compounds
to target
GABA and
depression,
and is
them,
treat patients
who
testingto
compounds
to target
aren’t
currentwho
drugs.
them,helped
to treatby
patients
In his
preliminary
research
aren’t
helped
by current
drugs.
with
animal
models,research
he
In his
preliminary
has
a linkhe
withestablished
animal models,
between
low levels
of GABA
has established
a link
and
depressed
mood.
His
between
low levels
of GABA
discovery
not only
provides
and depressed
mood.
His a
better
understanding
of the a
discovery
not only provides
biological
basis for symptoms
better understanding
of the
associated with depression,
but
also opens
to new
biological
basisthe
for door
symptoms
approaches
to more
effectively
associated with
depression,
treat
thisopens
mental
illness.
but also
the
door to new
The work of
Liu
and
approaches
toDrs.
more
effectively
Sibille,
which
links
symptoms
treat this
mental
illness.
toThe
biology,
their
workand
of Drs.
Liu and
progress
in developing
new
Sibille, which
links symptoms
medications
aretheir
enabled by
to biology, and
critical
support
from CAMH’s
progress
in developing
new
Campbell
Institute.
medications
are enabled.
Philanthropic investment
in the Campbell Institute fills
fills
important gaps in funding,
Dr. Sibille notes, allowing
researchers to accelerate their
discoveries and bring new
treatments “from the research
bench to the bedside.”
bedside.
The
power of
philanthropy
Visionary investment
drives change. At CAMH,
philanthropic investment in
research is changing what
is possible for mental illness
treatment, diagnosis and
prevention. The Campbell
Family, whose historic
$30-million gift in 2011
created the Campbell Family
Mental Health Research
Institute, is at the forefront of
a remarkable philanthropic
movement in support of
mental illness research. A
dedicated community of
donors is activating progress
in high-priority areas:
personalized medicine;
advanced brain imaging;
new drug development; early
intervention; and prevention.
“The Krembil Foundation
supports research at CAMH
because it effectively breaks
down research silos to bring
scientific fields
fields
multiple scientific
find solutions that
together to find
will have the greatest and most
rapid impact on patient care,”
says Mark Krembil, president
of the Krembil Foundation and
Chair of CAMH’s Research
Committee.
Through their generosity,
donors provide essential
support to enhance and
expand research facilities,
and recruit internationally
recognized scientists – like Dr.
Etienne Sibille, the Campbell
rst research chair.
Institute’s fifirst
There is now a growing
constellation of donorsupported, specialty-research
programs at CAMH, united
through the Campbell
Institute, which include the
Krembil Family Epigenetics
Laboratory, the Temerty
Centre for Therapeutic Brain
Stimulation, the Slaight Centre
for Youth in Transition, the
Research Imaging Centre and
the Tanenbaum Centre for
Pharmacogenetics.
breakthrough | CAMH
11
REVOLUTIONIZI NG T RE AT M E NT
Fahad’s uplifting
journey
How CAMH’s groundbreaking therapy brought joy
back to Fahad Alvi’s life BY WALLACE IMMEN
12 breakthrough | CAMH
Fahad Alvi is
back on track
after receiving
brain stimulation
therapy as part of
a new research
study.
mental illness treatment.
If successful, this research
could lead to a new, nonpharmaceutical approach for
youth who are experiencing
depression.
Says Temerty Centre
researcher Dr. Faranak
Farzan, who is leading
this study: “Conventional,
medications are not designed
for young people and have
significant
significant side effects. If our
results are positive, we will
have identifi
identified
ed a completely
new treatment specifically
specifically
for younger patients that will
be safer and more effective.
That would be a huge step
forward.”
Dr. Farzan’s study builds on
the groundbreaking success
of the Temerty Centre’s
research, which has proven
that rTMS is effective in
treating severe depression
in adult patients who do not
respond to other forms of
treatment. This discovery
represents one of the most
important advances in
psychiatry in decades.
“Depression is an illness
that desperately needs newer
advanced treatments,”
says Dr. Jeffrey Daskalakis,
co-director of the Temerty
Centre and chief of CAMH’s
mood and anxiety division.
Capitalizing on its
understanding of
neuroplasticity – the brain’s
ability to change itself – the
Temerty Centre is developing
new, non-pharmaceutical
options for serious mental
illness. The Centre was one
of the first
first in the world to
record plasticity in areas
of the brain that control
movement, as well as the
first in the world to record
first
plasticity from frontal brain
regions, the areas most
relevant to mental illness
research.
Progress in brain
stimulation research has led
to the approval of rTMS by
Health Canada as a therapy
for treatment-resistant
depression. It could soon
become an OHIP-billable
treatment.
“This will have
extraordinary impact,”
notes Dr. Daskalakis,
“because treatment-resistant
depression creates enormous
impact on people’s lives as
well as costs to the healthcare system and losses to the
economy.”
Other forms of brain
stimulation being studied at
the centre are proving to be
beneficial for treating some
beneficial
of the serious complications
associated with severe
mental illness.
Researchers at the Centre
discovered that Magnetic
Seizure Therapy (MST),
another form of brain
PHOTOGRAHY BY THOMAS BOLLMANN
Fahad Alvi was a happy,
energetic teenager in Toronto
with plenty of friends, but
after graduating from high
school, he noticed a marked
change in his mood.
“I started seeing myself as
a different person,” recalls
Fahad, who is now 20 years
old. “I was always exhausted
and I wasn’t able to get
enough sleep. I found myself
just closing off and I wouldn’t
go out or talk to my friends
anymore.”
Fahad was experiencing
the first
first signs of depression,
a disabling, often difficultdifficultto-treat mental illness that
affects about 8 per cent of
Canadians at some point
in their lives. Depression
can prevent sufferers from
working, completing school
and fulfilling
fulfilling their potential.
It can even increase the risk
for dementia later in life. And
medications and talk therapy
aren’t sufficient
sufficient to help many
people recover.
Fortunately, Fahad was
referred by his family
doctor to the Campbell
Institute’s Temerty Centre
for Therapeutic Brain
Intervention at CAMH,
where he received repetitive
transcranial magnetic
stimulation (rTMS) as part of
a new research study.
This is the first
first time a brief
form of rTMS is being used
in clinical research with
patients ages 16-24.
A form of non-invasive
brain stimulation therapy,
rTMS uses an electromagnet
placed on the scalp to deliver
deliver
brief, targeted pulses in rapid
succession to the brain.
The treatment’s ability to
effectively regulate electrical
communication within the
brain, without causing side
effects, is revolutionizing
BRAIN STIM ULAT I ON
Investigating
Alzheimer’s
Unique study at
CAMH could slow
the progression of
memory loss
PHOTOGRAHY BY ROGER YIP
Fahad Alvi
receives rTMS
treatment from
Dr. Faranak
Farzan, who
leads the
pioneering
study focused
on younger
patients.
stimulation therapy, has the life-saving
potential to prevent suicide.
Their research showed that more
than 75 per cent of the patients who
received MST experienced a complete
suppression of suicidal symptoms.
Brain stimulation therapy’s ability
to help the brain restore neural
connections and cognitive functions,
such as memory, provides the basis for a
promising new national study focusing
on Alzheimer’s disease prevention.
This study, led by a team of researchers
at CAMH, will combine brain
stimulation therapy with cognitive
skills development to prevent this
neuro-degenerative disease in
individuals at highest risk.
For patients like Fahad, one of the
most important benefits of brain
stimulation therapy is that its effects
are felt almost immediately. He found
that the series of daily rTMS treatments,
designed for him at the Temerty Centre,
created an almost immediate lifting of
his depression.
After only two weeks of treatments,
five times a week, “I noticed differences
in the way I approached problems and
thought about myself,” he says. “Before
Brain
stimulation
could become
a treatment to
prevent Alzheimer’s
the treatments, I would continually dwell
on things that were going wrong and I
didn’t have any confidence in myself.”
He says the treatment was so
comfortable that he sometimes fell
asleep during sessions, which can last
for up to 30 minutes. He felt only a slight
tingling during the treatments, but never
any pain from the magnetic pulses.
He reports being able to better
cope with situations that, in the past,
would have driven him deeper into
depression. This gave him the optimism
and confidence to decide to pursue a
university degree.
“I feel like the treatments opened up
my mind,” he says.
And it offers real hope for people
seeking new treatment options for
depression.
Brain stimulation therapy could
offer the first effective option
for delaying or even preventing
Alzheimer’s disease.
Alzheimer’s disease is the most
common form of dementia and affects
500,000 Canadians. This number will
increase as our population continues
to age. There are no cures or effective
treatments.
At CAMH’s Campbell Institute,
researchers are combining their
expertise in brain stimulation research
with the latest evidence linking
depression to an increased risk
for Alzheimer’s to develop a new
prevention strategy.
Building on the outstanding success
of its brain stimulation research and
its expertise in geriatric mental health
care, CAMH’s Campbell Institute
is now embarking on the country’s
largest Alzheimer’s disease prevention
research project.
Funded by Brain Canada and the
Chagnon Family, the study, unique
in Canada, will track the benefits of
combining brain stimulation therapy
with cognitive training exercises to help
prevent or delay Alzheimer’s disease in
those at high risk.
“By the time people develop
dementia, it may be already too late
to do anything about it,” says Dr.
Tarek Rajji, chief of CAMH’s Geriatric
Psychiatry Program and co-lead
investigator for the Alzheimer’s study.
“So prevention is important to try to
prevent its onset.”
The cognitive training exercises
will focus on developing participants’
memory skills and ability to complete
daily activities. After eight weeks of
treatments, patients continue to do
mental exercises at home, with followup assessments every six months.
breakthrough | CAMH
13
NEW FRONTIER S
The aging brain
Canadians are living longer than ever, but we know very little about
ng
the aging brain. At CAMH’s Campbell Institute, we are exploring
new territory that will lead to a better understanding of how age
ed
a ects the brain and how we can prevent and treat age-related
illnesses like Alzheimer’s disease.
10 per cent of seniors have a
mental illness
More than 75 per cent of
seniors living in long-term
care homes su er from
psychiatric symptoms related
to dementia
20
%
20 per cent of all suicides
in Canada occur in people
over the age of 60
4x
People who are depressed in
late life are up to 4 times more
likely to develop dementia
$33
BILLION
The total cost of dementia to
the nation
Sources: CAMH and the Alzheimer's
Society of Canada
14 breakthrough | CAMH
CAMH's Campbell Institute
Our progress in identifying risks and improving treatment
Understanding the cause
CAMH’s Campbell
Institute takes a
unique approach
to understanding
dementia,
combining both
genetics and brain imaging to pinpoint
cellular and structural changes that lead
to dementia.
BREAKTHROUGH
Brain imaging
research at CAMH’s
Campbell Institute
revealed that people
with Alzheimer’s
have higher levels of
brain inflammation. This discovery could
lead to new treatment approaches.
Improving treatment
Age can change
how people
respond to
medication,
increasing the
risk for negative side e ects. Researchers
at CAMH’s Campbell Institute are studying
how age a ects the metabolization of
drugs. This work will protect seniors and
reduce health-care costs.
Prevention
CAMH’s Campbell
Institute
is leading
Canada’s largest
Alzheimer’s disease prevention study. The
study combines cognitive exercises with
brain stimulation therapy to prevent this
disease in those at greatest risk.
Centre for Addiction and Mental Health
CAMH is the
leading Canadian
centre for
innovative care,
education and
research on
mental illness
and aging.
Delaying
Alzheimer’s
disease by two
years could save
the health-care
system
$15-billion.
Psychiatric
symptoms in
dementia are
a major cause
of premature
admission to
long-term care.
20 per cent of
hospital
admissions in
patients over
the age of 70 are
due to negative
drug reactions.
PHOTOGRAHY BY KEVIN HAND
10
%
75
%
B R E A K T H R O U G H C A M PA I G N
The Campbell Family Mental Health Research Institute is a catalyst in
creating and strengthening the centres of innovation at CAMH.
The network of centres includes The Margaret & Wallace McCain Centre for Child, Youth &
Family Mental Health; The Temerty Centre for Therapeutic Brain Intervention; The Tanenbaum
Centre for Pharmacogenetics; The Slaight Family Centre for Youth in Transition; and The Cundill
Centre for Child & Youth Depression.
Together, we are driving unprecedented progress in research, discovery, and care to improve
the lives of those living with mental illness.
Generous philanthropy at CAMH is inspiring hope.
www.supportcamh.ca/breakthrough
B R E A K T H R O U G H C A M PA I G N
The next breakthroughs will come from CAMH, Canada’s leading hospital
for mental health, thanks to donor support.
Fuelled by the $200 million Breakthrough Campaign, CAMH is able to help more people
recover faster by improving access to care. Thanks to your investment, we have raised $148
million to date as part of Canada’s largest campaign for mental health.
With your support, we will help more people recover, faster; inspire hope through discovery
and stop mental illness from destroying lives.
Please join us to fuel innovation. Invest in tomorrow’s breakthroughs, today.
www.supportcamh.ca/breakthrough