breakthrough breakthrough

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eakthrough

WINTER 2015/16

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

imaging tools

Transforming how the

world sees mental illness

Treating

depression in

youth without

medications

The brain’s role in depression

Alzheimer's disease:

New approach to prevention


BREAKTHROUGH CAMPAIGN

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 WINTER

12

4 Nature and nurture

11

How multiple factors in

childhood may affect the brain

in adulthood

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

2015/16

7 Big data

Bioinformatics mines and

analyzes genetic information

to reveal the cause of 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.

The

Campbell

Institute

paves the way

for a brighter

future

One in three Canadians

during One three their Canadians lifetime will during experience their lifetime a brain-related

will experience

illness,

a brain-related

such as

illness,

depression,

such as

schizophrenia,

depression, schizophrenia,

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

Mental

landmark

Health

donation

(CAMH).

to

This

the

gift

Centre

launched

for Addiction

the Campbell

and Family Mental Mental Health Health (CAMH). Research This Institute, gift launched where today the

Campbell there is a sense Family of excitement Mental Health and optimism, Research as Institute,

where groundbreaking today there discoveries a sense are of leading excitement to a better and

optimism, understanding as groundbreaking of mental illness. discoveries are leading to

a Consider better understanding depression. It’s of the mental leading illness. cause of

disability Consider globally, depression. but current It’s the treatments leading cause help only of half

disability of those with globally, the illness. but current At the Campbell treatments Institute, help we’ve only

half developed of those a chemical with the brain illness. probe, At the which Campbell showed, Institute, for

we’ve the first developed time, evidence a chemical of inflammation brain probe, in the which brains of

showed, those with for depression. the first time, evidence of inflammation

in Our the continued brains of exploration those with depression.

of this discovery could lead to

an Our entirely continued new way exploration of treating depression.

of this discovery could

lead The to questions an entirely we’re new investigating, way of treating highlighted depression. in this

magazine, The questions are provocative we’re investigating, and paradigm-shifting. highlighted Can in we

this

prevent

magazine,

the development

are provocative

of mental

and

illnesses?

paradigm-shifting.

Can treating

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

translating

The Campbell

breakthroughs

Institute

in


the

which

lab into

brings

new

together

options

the

latest for patient brain care. science With this technologies pace of progress, and expertise we can offer in

genetics, Canadians molecular hope for the science future and stop brain mental imaging illness – is from

successfully destroying lives. translating breakthroughs in the lab into

new options for patient care. With this pace of progress,

we

Bruce

can

G.

offer

Pollock,

Canadians

MD, PhD,

hope

FRCPC

for the future and stop

mental illness from destroying lives.

Vice-President, Research, CAMH

Bruce Director, G. Campbell Pollock, Family MD, PhD, Mental FRCPC Health Research Institute

Vice-President, Research, CAMH

Director, Campbell Family Mental Health Research Institute

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

EDITOR

Elizabeth Holland

ART DIRECTOR

Kamille Chin

CONTRIBUTORS

Thomas Bollmann,

Brenda Bouw, Dali Castro,

Mary Gooderham,

Kevin Hand, Wallace

Immen,

Immen,

June

June

Rogers,

Rogers,

Roger Yip

Roger Yip

PUBLISHERS

Caroline Riseboro, Lori

Spadorcia, Susan Mullin

CAMH EDITORS

Teresa Marques, Robin

Rowe, Danielle Donadio,

Anita

Anita

Dubey,

Dubey,

Valerie

Valerie

Meek,

Meek,

Kate Richards

Kate Richards

SPECIAL THANKS to to CAMH staff,

staff, clinicians, researchers and

clinicians,

patients who

researchers

shared their

and

stories

patients in this publication.

who shared their stories

in this publication.


THE GLOBE EDGE TEAM

Teena Poirier

Director, Content Marketing Group

Sean Stanleigh

Managing Editor,

Managing Editor,

Globe Content Studio

Globe Content Studio

Michael Grier

Director,

Michael

Business

Grier

Development

Director, Business Development

Liz Massicotte

Program Liz Massicotte Manager, Globe Edge

Program Manager, Globe Edge

Sally Pirri

Director, Sally Pirri Production,

The Globe And Mail

Director, Production,

Isabelle

The Globe

Cabral

And Mail

Production Co-ordinator

The

Isabelle

Globe

Cabral

And Mail

Production Co-ordinator

The Globe And Mail

breakthrough | CAMH 3


Nature and nurture

Early findings of landmark study show multiple factors in

childhood can lead to mental illness in adulthood

New research

reveals how

genes and

early childhood

experiences can

increase the risk

for mental illness.

Dr. Robert Levitan of CAMH’s Campbell

study, we’re going back to understanding

Family Mental Health Research

how it all started.”

Institute has spent his career seeking

The MAVAN project is a novel example

to better understand the origins of his

of how researchers are combining

adult patients’ illnesses and the often-

expertise in a range of specialties

common link between mood disorders

including developmental neurobiology,

and overeating and obesity.

genetics, attachment theory, and

Through his work with a landmark

nutrition, to unlock the complexity of

Canadian study, Dr. Levitan is gaining

psychiatric problems.

new insight into the earliest origins

By investigating weight regulation

of illness and is encouraged by new

and eating behaviours in childhood,

research findings showing how the

Dr. Levitan can better understand the

exchange between both genetic and

link between depression and obesity

environmental factors increase risk.

in adults. His recent research, looked

“The whole dance of nature and

at maternal sensitivity – how attuned a

nurture is more multidirectional than

mother is to her child – and found that

one might have thought,” he says.

girls who experienced low maternal

Dr. Levitan is part of the Maternal

sensitivity at six months of age had

Adversity, Vulnerability and

higher body mass index (BMI) scores

Neurodevelopment (MAVAN) study,

at 48 months.

which is investigating the interplay

In a follow-up study, he also found

between genes and environment in

this link occurred only in girls with a

nearly 550 children and their mothers –

particular variation of a gene called the

tracking children’s development over the

dopamine-4 receptor gene, or DRD4.

course of several years.

“This suggests that it’s the combination

Along with his Canadian colleagues,

of a certain gene and a certain

Dr. Levitan is gathering compelling

environment that may lead to obesity,

evidence that early childhood

rather than either alone,” he says.

experiences, mother-infant interactions

“The positive message in this is that

and genetic susceptibility increase the

we are really getting to understand the

risk for mental illness later in life.

human brain as well as vulnerability and

“A lot of research to date is in

resilience, which will help us develop

understanding the advanced stages of

new treatments and approaches,” says

diseases,” he explains. “With the MAVAN

Dr. Levitan. “It’s a message of hope.”

—Brenda Bouw

Canada’s

leader

CAMH’s Campbell

Family Mental Health

Research e

Institute

t

excels e in n genetics,

e

i

brain i imaging i g and

molecular l science,

i

e

and features:

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 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.

4 breakthrough | CAMH


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

Dr. Romina

Mizrahi seeks

new ways

to prevent

schizophrenia

in young

people.

teens and early

20s and, if not

identified and

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 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

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

a final third, the symptoms go away on

their own.

“We are now aiming within five years

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

very confident, because we are getting

so close.”

—Wallace Immen

Picture

this

Radiotracers ace r

developed e d at CAMH’s Campbell Institute t t

help

researchers e r ers around the world unlock the mysteries es of the brain

PHOTOGRAHY BY THOMAS BOLLMANN

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 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, 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 inflammation 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


GAME-CHANGERS

Dr. Jeffrey Meyer,

senior scientist at

CAMH’s Campbell

Institute, is proving

that depression isn’t

a “one-size-fits-all”

illness.

Emerging discoveries

CAMH’s Campbell Institute’s leading-edge research explains

the biology behind depression

BY BRENDA BOUW

Some of the most groundbreaking

are probably multiple ways,” he

research on depression being

explains.

conducted today doesn’t involve

Dr. Meyer’s research led to several

a specific treatment or drug, but

new discoveries on what causes

instead the discovery that there are

depression using positron emission

multiple changes in the brain that

tomography (PET) brain imaging and

can trigger this mental illness.

chemical probes created at CAMH’s

Thanks to leading-edge studies

Campbell Institute.

conducted by Dr. Jeffrey Meyer,

These sophisticated brain-imaging

senior scientist at CAMH’s Campbell

techniques have revealed that

Institute, researchers are discovering

depression can vary significantly

a remarkable variety of biological

depending on factors such as the age

causes behind depression.

and sex of the patient.

The trailblazing research, which

His two broad areas of discovery

shows that depression isn’t a “one-

include MAO-A (an enzyme

size-fits-all” illness, is expected to

that breaks down chemicals like

have a profound impact on how

serotonin and dopamine) and brain

doctors will diagnose and treat

inflammation.

mental illness.

He was the first to show that in

“Our understanding about

major depression, the MAO-A level

depression is evolving,” says Dr.

was significantly higher in every

Meyer, who has spent most of his

brain region. Higher MAO-A levels

career studying mood disorders.

lead to increased breakdown of

The science has changed

key mood-regulating chemicals

dramatically from past theories that

like serotonin.

depression was caused solely by low

Dr. Meyer has shown that MAO-A

serotonin in the brain, he says.

was increased in people with

“There isn’t one way a person gets

seasonal affective disorder, in women

clinical depression biologically; there

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

high rates of first-time depression

among women experiencing

perimenopause.

It was the first time that a

biological change in the brain has

been identified in perimenopause

and may explain the onset of

first-time depression in women

of this age group.

In a new world first, Dr. Meyer

recently proved the link between

brain inflammation and depression.

His study showed that brain

inflammation 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 findings 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

6 breakthrough | CAMH


RESEARCH REVOLUTION

Computing

genes

PHOTOGRAHY BY ROGER YIP

Big data,

huge impact

Leading-edge technologies

are opening new frontiers

of discovery

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,

brain overlap with – and says the institute

may in fact promote –

is “a hub of

neuropsychiatric diseases. ingenuity.”

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 five-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

chance of developing

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.

These findings are part of

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

more efficient in treatments,”

says Dr. Petronis.

—Wallace Immen

breakthrough | CAMH 7


IN BRIEF / TAG

Dr. Jim Kennedy, head

of the Campbell Institute’s

Tanenbaum Centre for

Pharmacogenetics:

“Personalized medicine

will be a life-changer.”

PHOTOGRAHY BY NAME NAME

8 breakthrough | CAMH


PERSONALIZED MEDICATIONS

Tailor-made

treatment

Genetic-testing tools make medications more effective for patients

BY JUNE ROGERS

PHOTOGRAHY BY THIOMAS BOLLMANN

KRISTIN MACPHERSON GREW UP IN

IN A CARING, A CLOSE-KNIT FAMILY. Her

father Her father was was a highly a highly respected respected cardiologist

and cardiologist internist, and her internist, mother a her journalist. mother a

At journalist. Branksome At Branksome Hall, a private Hall, school a private for

girls school in for Toronto, girls in she Toronto, excelled she in excelled art and

sports, in art and especially sports, especially cross-country country reached skiing. the She top reached of her class the top in her of

skiing.

She

last her class year of in high her last school. 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 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.”

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.

“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 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 receptor and genes receptor help genes predict to which

help medications predict which will be medications effective, as well will as

be how effective, the liver as metabolizes well as how drugs. the liver

metabolizes If the liver processes drugs. a drug too

quickly, If the liver then processes it doesn’t a remain drug too in the

quickly, body long then enough it doesn’t to reach remain the brain the

body and be long effective. enough If to it takes reach longer, the brain then

and too much be effective. of the drug If it takes accumulates longer, then in

too the body, much causing of the drug side accumulates effects such in

the as nausea, body, causing dizziness, side lethargy effects such and

decreased nausea, libido. dizziness, lethargy and

decreased The IMPACT libido. study’s goal is to screen

breakthrough | CAMH 9


PERSONALIZED TREATMENT

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

DNA screening coming

soon to doctors’ offi ces

20,000 The IMPACT patients, study’s ages 7 goal to 79, is by to 2018. screen So

far, 20,000 more patients, than 3,840 ages patients 7 to 79, by have 2018. taken So

the far, more test. Since than family 3,840 patients doctors have prescribe taken

80 the per test. cent Since of psychiatric family doctors medications, prescribe

the 80 per test cent has of been psychiatric made available medications, to

more the test than has 1,100 been doctors made available in Ontario. to

About more than 800 of 1,100 those doctors physicians in Ontario. surveyed

have About reported 800 of those that 70 physicians per cent surveyed of their

patients have reported have experienced that 70 cent significant of 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 on a the family IMPACT doctor study at Thornhill is Dr. Nick

Medical Voudouris, Centre. a family doctor at Thornhill

Medical “We’ve Centre. taken this personalized

medicine “We’ve taken approach this personalized

to a suburban

clinical medicine setting,” approach says to Dr. a suburban Voudouris,

“where clinical we setting,” see every says nationality Dr. Voudouris, and a

variety “where of we mental see every health nationality issues.” and a

variety As part of of mental the IMPACT health issues.” study, Dr.

Voudouris As part of receives 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 days tailored that indicates to his patient’s which medications

genotype

using are tailored stop-light 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 for longer caution a cookie-cutter

and red for stop.

situation,” “It’s no longer says Dr. a cookie-cutter

Voudouris. “We now

situation,” know what says medications Dr. Voudouris. and dosages “We now will

know be effective.” what medications and dosages will

be The effective.” genetic testing reassures his

patients The genetic with scientific testing reassures proof that his

patients their prescriptions with scientific are tailored proof that to

their DNA, prescriptions he says. are tailored to

their “I have DNA, one he patient says. who saw the list

of “I his have ‘green’ one medications patient who and saw said the list

of he his wanted ‘green’ to medications try all of them and until said he

reached wanted a 10 to out try all of 10 of them and felt until well he

reached again,” says a 10 Dr. out Voudouris. of 10 and felt well

again,” “There’s says an Dr. art Voudouris.

in helping to convince

people “There’s to take an art medications in helping to in convince the first

people place,” he to take adds, medications “and this genetic in the first

place,” testing has he adds, made “and it much this genetic easier for

testing people has to accept.” made it much easier for

people Being to among accept.” the first patients to

benefit Being 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 confidently – that her say life – has and

changed her sister, for Bryn, the agrees better. – that her life has

changed She sings for in the a choir, better. swims at the

YMCA She sings and has in a volunteered choir, swims at at CAMH the YMCA

for and speaking has volunteered engagements for CAMH for young speaking

people to young and people law enforcement and law enforcement officers. “I

hope officers. that “I future hope that generations future generations

with mental

illnesses with mental will illnesses have it 10 will times have easier it 10 than

I times 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

10 breakthrough | CAMH


NEW APPROACH TO DRUG DEVELOPMENT

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

Senior

of its functions or signalling

scientist

pathways.

Senior

Dr. scientist Fang Liu

The medication can treat is Dr. studying Fang Liu

the unwanted symptom but how is studying cells

ends up producing other

communicate

how cells

effects, like the slow gait

with communicate each

common in people being

other, with each with

other, goal with of

treated for schizophrenia.

the developing

Dr. Liu’s research

goal of

developing

medications

has produced a new

medications

without

understanding of different without adverse side

protein complexes linked

adverse effects. side

to illnesses. Based on this

understanding, it is possible

to “disrupt” the protein and

target one 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

effects.

the peptide to precise

the areas peptide of the to brain. precise

areas Her of colleague, brain. Dr. Etienne

Sibille, Her colleague, the Campbell Dr. Etienne Family

Sibille, Chair in the Clinical Campbell Neuroscience, Family

Chair is studying Clinical the connection Neuroscience,

is between studying the the neurotransmitter

connection

between GABA and the depression, neurotransmitter and is

GABA testing and compounds depression, to target and is

testing them, to compounds treat patients to target who

them, aren’t helped to treat by patients current who drugs.

aren’t In his helped preliminary by current research drugs.

with In his animal preliminary models, research he

with has established animal models, a link he

has between established low levels a link of GABA

between and depressed low levels mood. of GABA His

and discovery depressed not only mood. provides His a

discovery better understanding not only provides of the a

better biological understanding basis for symptoms of the

associated with depression,

biological but also opens basis the for door symptoms

new

associated approaches with to more depression, effectively

but treat also this opens mental the illness. door to new

approaches The work of to Drs. more Liu effectively and

treat Sibille, this which mental links illness. symptoms

to The biology, work and of Drs. their Liu and

Sibille, progress which in developing links symptoms new

to medications biology, and are their enabled by

progress critical support in developing from CAMH’s new

medications Campbell Institute. are enabled.

Philanthropic investment

in the Campbell Institute 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.”

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

multiple scientific c fields

together to find solutions that

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

Institute’s first research chair.

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


REVOLUTIONIZING TREATMENT

Fahad’s uplifting

journey

How CAMH’s groundbreaking therapy brought joy

back to Fahad Alvi’s life BY WALLACE IMMEN

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 signs of depression,

a disabling, often difficultto-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 their potential.

It can even increase the risk

for dementia later in life. And

medications and talk therapy

aren’t 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 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

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

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 side effects. If our

results are positive, we will

have identified a completely

new treatment 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,

Fahad Alvi is

back on track

after receiving

brain stimulation

therapy as part of

a new research

study.

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 in the world to

record plasticity in areas

of the brain that control

movement, as well as the

first in the world to record

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

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

12 breakthrough | CAMH


BRAIN STIMULATION

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 benefi ts 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 FRONTIERS

The aging brain

Canadians are living longer than ever, but we know very little about

the aging brain. At CAMH’s Campbell Institute, we are exploring

new territory that will lead to a better understanding of how age

a ects the brain and how we can prevent and treat age-related ed

illnesses like Alzheimer’s disease.

CAMH's Campbell Institute

Our progress in identifying risks and improving treatment

10 per cent of seniors have a

mental illness

10 % about

Understanding the cause

Improving treatment

75 %

More than 75 per cent of

seniors living in long-term

care homes su er from

psychiatric symptoms related

to dementia

20 %

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

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

20 per cent of all suicides

in Canada occur in people

over the age of 60

4 x

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

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.

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.

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.

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

14 breakthrough | CAMH


BREAKTHROUGH CAMPAIGN

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


BREAKTHROUGH CAMPAIGN

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

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