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Personalized medicine for the brain: A call for action



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.
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:
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.
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
2010 Nature Publishing Group All rights reserved 1359-4184/10
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 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/
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,
(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-
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.
Dr LM Williams is at the BRAINnet
Foundation, Sydney Medical School,
University of Sydney at Westmead
Hospital, Sydney, Australia.
Dr E Gordon is at Brain Resource Ltd,
Headquarters at Sydney, Australia
and San Francisco, USA.
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achieve a significant understanding of which out-comes will directly translate into the clinic and into novel treatments. Essential to integration and capac-ity for translation and replication of research results are platforms that support standardization, sharing, and collation of objective data across modalities, scales, and large number of subjects (13). The BRAINnet Foundation goal is to understand mental illness as a human brain disease and to ulti-mately discover how to prevent and cure these illnesses; this is accomplished through open electronic sharing and continued expansion of a global database of human brain data in health and disease across the life span. It is a 501(c) 3 US-Based Tax Exempt Research Foundation, with these unique features: (i) standardized protocols and assessment platforms so that data can be pooled across disorders, sites, and studies and (ii) multiple types of data spanning clinical, behavioral, physiological, imaging, and genomic domains in the same subjects. These domains align with those of NIMH's Research Domain Criteria (RDoC), (iii) open sharing of data without needing to contribute new data, and (iv) network of collaborating researchers, for seeking grant support to carry out studies, drawing on existing data and standardized methods. The BRAINnet methods span self-report scales, computerized behavioral measures of cognition and emotion, physiology (EEG, ERP, and concurrent autonomic recordings), magnetic resonance imaging (structural, functional, and diffusion tensor imaging), and salivary or blood draws for genotyping. Currently, data are available for 5,092 healthy subjects and others from specific disorders. Recent outcomes from the published studies using BRAINnet data demonstrate how the stan-dardized approach is a quality and efficient way to take a lead in initiatives being forged in psychiatry and neuroscience, such as NIMH's RDoC, to identify biomarkers that will make a difference in under-standing the cause of mental illness, tailoring current treatments, and developing novel ones.
American Foundation for Suicide Pre- vention)
  • Paula Clayton
  • Md
Paula Clayton, MD (American Foundation for Suicide Pre- vention);
PhD (MDV-Mohr Davidow Ventures)
  • T Katherine
  • Moortgat
Katherine T Moortgat, PhD (MDV-Mohr Davidow Ventures);
Stephen Whisnant (United States Institute of Peace)
  • Phillip Wang
Phillip Wang, MD (NIH); Stephen Whisnant (United States Institute of Peace); David Whitehouse, MD (OptumHealth Behavioral Solutions); Peter C Whybrow, MD (UCLA Center for Health Sciences Neuropsychiatric Institute);
PhD (American Association for the
  • Deborah Runkle
Deborah Runkle, PhD (American Association for the Advancement of Science);
OptumHealth Behavioral Solutions & University of Missouri-Columbia School of
  • George Viamontes
  • Phd Md
George Viamontes, MD, PhD (OptumHealth Behavioral Solutions & University of Missouri-Columbia School of Medicine);
United States Institute of Peace)
  • Stephen Whisnant
Stephen Whisnant (United States Institute of Peace);