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Personalized medicine for the brain: A call for action

March 2010
Molecular Psychiatry 15(3):229-30

DOI:10.1038/mp.2009.147

Source
PubMed

Authors:

Stephen H Koslow

Otsuka America Pharmaceutical

Leanne M Williams

Stanford University

Evian Gordon

The Brain Resource Company

Disorders of the human brain, such as depression, schizophrenia and addiction, are the cause of immeasurable human suffering. As they are largely chronic and strike in youth, brain disorders lead to greater disability and loss of productivity than any other category of illness. On 24–25 October 2009, leaders from the fields of research, medicine, industry, government and philanthropy convened at the Mayflower Hotel in Washington DC to launch an initiative fostering personalized medicine for the brain. The Mayflower Action Group Initiative was instigated by BRAINnet, a new non-profit foundation that provides a database on the human brain using standardized methods.

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NEWS AND COMMENTARY

Brain personalized medicine

......................................

Personalized medicine for the brain:

a call for action

SH Koslow, LM Williams and E Gordon

.......................................................................

Molecular Psychiatry (2010) 15, 229–230; doi:10.1038/mp.2009.147; published

online 12 January 2010

Disorders of the human brain, such

as depression, schizophrenia and

addiction, are the cause of immea-

surable human suffering. As they are

largely chronic and strike in youth,

brain disorders lead to greater dis-

ability and loss of productivity than

any other category of illness. On 24–

25 October 2009, leaders from the

fields of research, medicine, indus-

try, government and philanthropy

convened at the Mayflower Hotel

in Washington DC to launch an initi-

ative fostering personalized medi-

cine for the brain. The Mayflower

Action Group Initiative was insti-

gated by BRAINnet, a new non-profit

foundation that provides a database

on the human brain using standar-

dized methods.

The Mayflower Action Group

advocates the following actions to

make personalized medicine for

the brain a reality:

Integrate

Study the brain as a system: The

brain is highly connected and en-

ormously complex, so it must be

studied as a system. Studying

genes alone is not enough. Multiple

levels of information—from genes

to brain structure, brain function,

cognitive performance and symp-

toms—must be brought together.

Ultimately, the brain’s actions must

be captured in real time.

Look at variables in combination:

Study composite effects rather than

factors in isolation. For example,

studying the variations in multiple

genes will better explain the long-

term molecular effects of early

childhood trauma and how innate

biology interacts with the environ-

ment to heighten individuals’ pre-

disposition to depression.

Dismantle silos: In addition to

bringing together data, it is urgent

to bring together people: geneticists

and neuroscientists, clinicians and

the pharmaceutical industry, fun-

ders of healthcare and funders of

research, regulators and policy ma-

kers, and, crucially, patients. Much

more can be achieved by aligning

all stakeholders.

Standardize

Collect and bring together standar-

dized data: Standardized measure-

ment methods allow data to be

pooled and compared. Making ag-

gregated information accessible can

reveal how to make real differences

now. Consistent, standardized mea-

surements will shed light on the

defining characteristics of disorders

and will for the first time allow

researchers to compare the basis of

seemingly disparate disorders.

Reconsider diagnostic classifica-

tion systems: Disease will increas-

ingly be defined at the level of

genes and brain biology and may

lead to whole-scale changes in the

categorization of disorders.

Represent real populations

Clinical studies should represent

patients as a whole, not just as

‘pure’ cases, so that results in fact

apply to real people. In brain dis-

orders, co-morbidity is the norm.

Yet, studies on depression, for

example, routinely leave out those

who abuse substances, have post-

traumatic stress or anxiety disor-

ders, a known risk of suicide, or

physical ailments, such as diabetes

or heart disease.

Meet real-world needs

Distill information for clinical prac-

tice: Massive amounts of heteroge-

neous information must be

translated into specific guidelines

and measurement tools for health

care and done so rapidly. Patients

should benefit from the efficacy

and safety that the full range of

existing knowledge can support.

For example, genetics can identify

who will benefit from medications

for addiction, and heart rate varia-

bility training can be used to

reduce stress and chronic pain,

but such knowledge is rarely put

into practice and when it is, the

transition is slow.

Meet the consumer revolution:

Whereas doctors, politics and

health-care agencies are slow to

change, consumers have already

harnessed the power of instanta-

neous and widespread access to

knowledge through the internet and

increasingly demand treatments that

will work best for them with the

least side effects. In the case of

depression, for example, there is no

way to predict which patient will

respond to which therapy the first

time. That needs to change.

Harness the power of numbers

Use databases: Databases should

bring together complex information

obtained in rigorously controlled

and standardized ways. Large

pools of layered data that are made

widely accessible can reveal con-

nections in information. Data that

are gathered well and replicated

become the arbiter of what works

and how well. For example, cogni-

tive problems in schizophrenia

predict disruptions in patients’

lives, but treatments rarely cure

these problems. Variations in ill-

ness course and treatment response

Molecular Psychiatry (2010) 15, 229– 230

32.00

www.nature.com/mp

may well reflect differences in gene

expression, and large-scale analy-

sis is needed to drill down to that

level of understanding.

Solutions: We need to implement

the current solutions that have de-

monstrated significant potential to

screen for risk and predict

treatment outcomes. Solutions pro-

viding benefits now need to be more

clearly delineated from those requir-

ing more research. A move to elec-

tronic health records can be paired

with new tools and solutions. Web-

based screening measurements and

treatment algorithms should be in-

tegrated with health records.

Personalizing medicine in brain

research must be a long-term com-

mitment. The brain is too impor-

tant not to have the collective

attention of those who understand

aspects of this enormously com-

plex system and care about the

great human toll of its disorders.

The path to more effective treat-

ment is the rigorous collection of

information about the brain at

every available level of knowledge.

The BRAINnet database is one

effort toward this goal. It collects

data using highly standardized

methods that are agreed upon by a

group of expert users. Researchers

are invited to obtain free access to

data about the human brain at

BRAINnet.net. BRAINnet currently

includes 200 collaborators and data

from 10 000 people and is growing

rapidly. Researchers can use BRAIN-

net data to answer their own ques-

tions and its standardized methods

to acquire new data. BRAINnet is

one approach to encouraging large,

strategically designed studies that

will help speed the translation of

basic science into medicine, which

can make a personalized difference

in human lives.

Organized and prepared by: Ste-

phen H Koslow, PhD and Leanne

Williams, PhD, BRAINnet, Evian

Gordon Brain Resource Ltd, with

Karin Jegalian, PhD, Science Writer/

Editor.

BRAINnet Foundation is grateful

to Brain Resource Ltd for sponsor-

ing this meeting and delivering the

consented data and database to

BRAINnet Foundation for transpar-

ent governance and use by the

scientific community.

Participants: Edward Abrahams,

PhD (Personalized Medicine Coali-

tion); Edward Allera (Buchanan

Ingersoll, Rooney); Larry Alphs,

MD, PhD (Ortho-McNeil Janssen

Scientific Affairs); Eugene Baker,

PhD (OptumHealth Behavioral So-

lutions); Charles M Beasley, Jr, MD

(Eli Lilly and Company); Linda S

Brady, PhD (NIH); H Westley Clark,

MD, JD, MPH, CAS, FASAM

(HHS); Paula Clayton, MD (Amer-

ican Foundation for Suicide Pre-

vention); John P Docherty, MD

(New York-Presbyterian/Weill Cor-

nell); Katie Doll (OptumHealth Be-

havioral Solutions); Richard

Givertz, PhD (Alliant University);

Evian Gordon, MD, PhD (Brain

Resource Ltd); Steven Grant, PhD

(NIH); John F Greden, MD (Uni-

versity of Michigan); Henry Harbin,

MD, John Hollister, MD (NARSAD);

Shitij Kapur, PhD (Institute of

Psychiatry, London); Helen Karuso

(Australian Trade Commission,

Washington, DC); Stephen H Ko-

slow, PhD (BRAINnet); Julio Lici-

nio, MD (Australian National

University); Jeffrey Alan Lieber-

man, MD (Columbia University);

Norman Moore, MD (East Tennes-

see State University); Katherine

T Moortgat, PhD (MDV-Mohr Davi-

dow Ventures); Charles B Nemer-

off, MD, PhD (University of

Miami); Charles P O’Brien, MD,

PhD (University of Pennsylvania);

Herbert Pardes, MD (New York—

Presbyterian Hospital); Joseph

Parks, MD (Missouri Department

of Mental Health); Robert Paul,

PhD (University of Missouri—

St Louis); Joseph Perpich, MD, JD

(JG Perpich, LLC); Frida E. Polli,

PhD (Massachusetts Institute of

Technology); John VW Reynders,

PhD (Johnson & Johnson); Rhonda

Robinson-Beale, MD (OptumHealth

Behavioral Solutions); Deborah

Runkle, PhD (American Associa-

tion for the Advancement of

Science); Sunil Sachdev, MD (Op-

tumHealth Behavioral Solutions);

Steven Secunda, MD (Steven Se-

cunda Associates, Pennsylvania);

Sue Siegel (MDV-Mohr Davidow

Ventures); Steven Silverstein, PhD

(University of Medicine & Dentis-

try, New Jersey); Madhukar H Tri-

vedi, MD (University of Texas

Southwestern Medical School);

George Viamontes, MD, PhD (Op-

tumHealth Behavioral Solutions &

University of Missouri—Columbia

School of Medicine); Phillip Wang,

MD (NIH); Stephen Whisnant (Uni-

ted States Institute of Peace); David

Whitehouse, MD (OptumHealth

Behavioral Solutions); Peter C

Whybrow, MD (UCLA Center for

Health Sciences Neuropsychiatric

Institute); Leanne Williams, PhD

(BRAINnet & University of Sydney

Medical School).

For additional information, con-

tact BRAINnet@brainnet.net.

Conflict of interest

SHK employed as the Research

Director for the American Founda-

tion for Suicide Prevention, serves

as a Director for BRAINnet, re-

ceives a consultation fee for work

with Brain Resource as a science

consultant, and is a small equity

holder (stock options) in Brain

Resource. LMW is a small equity

holder in Brain Resource and Chair

of BRAINnet, and has received fees

from Brain Resource for projects

and consultancy unrelated to the

Washington meeting. EG is the CEO

and Chairmen of Brain Resource

Ltd and has significant equity and

stock options in the company.

Dr SH Koslow is at the BRAINnet

Foundation, 250 W 93rd Street,

Suite 12E, New York, NY 33412, USA.

E-mail: stephen.koslow@brainnet.net

Dr LM Williams is at the BRAINnet

Foundation, Sydney Medical School,

University of Sydney at Westmead

Hospital, Sydney, Australia.

E-mail: lea.williams@brainnet.net

Dr E Gordon is at Brain Resource Ltd,

Headquarters at Sydney, Australia

and San Francisco, USA.

E-mail: eviang@brainresource.com

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