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					  The
Quarterly     Spring 2011




                            RESEARCH NEWS
                    2       RESEARCH DISCOVERIES IN THE NEWS

                    5       INTERVIEW WITH A RESEARCHER
                            Bryan L. Roth, M.D., Ph.D.

                    9       ASK THE RESEARCHER

                    10      CAMPAIGN FOR PRODUCTIVE LIVES

                    12      FREQUENTLY ASKED QUESTIONS
                            ON MENTAL HEALTH

                    28      NEW TREATMENTS/THERAPIES
                            Breakthroughs continue to be made

                    30      MOMENTUM
                            Events Calendar
                            Sampling of Healthy Minds Across America Symposia

                    34      GLOSSARY

                    36      MEET A YOUNG INVESTIGATOR
                            Karuna Subramaniam, Ph.D.

                            FEATURE: New Hope in Mental Health


        FOCUS       16      PUBLIC SECTOR PERSPECTIVE
                            Thomas Insel, M.D., Director, NIMH
                                                                           SPECIA
                                                                                  L
                                                                           F E AT U
                                                                                      RE
         on         19      PRIVATE SECTOR PERSPECTIVE
                            J. Randolph Lewis, Senior VP, Walgreen, Co.

    NEW HOPE
         in
                    22      RESEARCH PERSPECTIVE
                            Carol A. Tamminga, M.D., Member,
                            Brain & Behavior Research Foundation Scientific Council

MENTAL HEALTH       24      FAMILY PERSPECTIVE
                            Constance E. Lieber, President Emerita,
                            Brain & Behavior Research Foundation

                    26      NONPROFIT SECTOR PERSPECTIVE
                            Kenn Dudek, President, Fountain House
Board of Directors
OFFICERS                          DIRECTORS                          PRESIDENT EMERITA
Chairman                          Anne E. Abramson                   Constance E. Lieber
Stephen Lieber                    Mark H. Alcott, Esq.
                                  Bonnie D. Hammerschlag
President and CEO                 George B. Handran, Esq.            DIRECTORS EMERITI
Benita Shobe                      Ken Harrison                       Hal B. Hollister
                                  Milton Maltz                       Patsy Hollister
Vice President                    Marc R. Rappaport                  Tamar Maltz
Suzanne Golden                    Barbara K. Streicker               Jeanne P. Robertson
                                  Robert S. Warshaw, Esq.            Shari Staglin
Secretary
John B. Hollister

Treasurer
Arthur Radin, CPA



Scientific Council
President
Herbert Pardes, M.D.
Vice President Emeritus
Floyd E. Bloom, M.D.

George K. Aghajanian, M.D.        Jay Adam Gingrich, M.D., Ph.D.     Paul R. McHugh, M.D.
Schahram Akbarian, M.D., Ph.D.    Alexander H. Glassman, M.D.        Ronald McKay, Ph.D.
Huda Akil, Ph.D.                  Frederick K. Goodwin, M.D.         James H. Meador-Woodruff, M.D.
Susan G. Amara, Ph.D.             Anthony A. Grace, Ph.D.            Herbert Y. Meltzer, M.D.
Stewart A. Anderson, M.D.         Paul Greengard, Ph.D.              Karoly Mirnics, M.D.
Nancy C. Andreasen, M.D., Ph.D.   Suzanne N. Haber, Ph.D.            Bita Moghaddam, Ph.D.
Jay M. Baraban, M.D., Ph.D.       Philip D. Harvey, Ph.D.            Dennis L. Murphy, M.D.
Jack D. Barchas, M.D.             Stephan Heckers, M.D.              Charles B. Nemeroff, M.D., Ph.D.
Samuel H. Barondes, M.D.          Rene Hen, Ph.D.                    Eric J. Nestler, M.D., Ph.D.
Francine M. Benes, M.D., Ph.D.    Fritz A. Henn, M.D., Ph.D.         Andrew A. Nierenberg, M.D.
Wade H. Berrettini, M.D., Ph.D.   Robert M. A. Hirschfeld, M.D.      Patricio O’Donnell, M.D., Ph.D.
Randy D. Blakely, Ph.D.           Steven E. Hyman, M.D.              Steven M. Paul, M.D.
Pierre Blier, M.D., Ph.D.         Robert B. Innis, M.D., Ph.D.       Godfrey Pearlson, M.D.
Robert W. Buchanan, M.D.          Jonathan A. Javitch, M.D., Ph.D.   Daniel S. Pine, M.D.
Peter F. Buckley, M.D.            Daniel C. Javitt, M.D., Ph.D.      Michael I. Posner, Ph.D.
William E. Bunney, Jr., M.D.      Lewis L. Judd, M.D., D.Sc. (Hon)   Robert M. Post, M.D.
                                                                                                                The
Joseph D. Buxbaum, Ph.D.
William F. Byerley, M.D.
                                  Peter W. Kalivas, Ph.D.
                                  Eric R. Kandel, M.D.
                                                                     Steven G. Potkin, M.D.
                                                                     Pasko Rakic, M.D., Ph.D.
                                                                                                             Quarterly
Marc G. Caron, Ph.D.              Richard S. E. Keefe, Ph.D.         Judith L. Rapoport, M.D.
William T. Carpenter, Jr., M.D.   Samuel J. Keith, M.D.              Perry F. Renshaw, M.D., Ph.D., M.B.A.   Credits
Cameron S. Carter, M.D.           Martin B. Keller, M.D.             Kerry J. Ressler, M.D., Ph.D.
BJ Casey, Ph.D.                   John R. Kelsoe, M.D.               Carolyn B. Robinowitz, M.D.             WRITERS:
Dennis S. Charney, M.D.           Kenneth S. Kendler, M.D.           Bryan L. Roth, M.D., Ph.D.              Judith N. Schwartz
Bruce M. Cohen, M.D., Ph.D.       James L. Kennedy, M.D.             John L. R. Rubenstein, M.D., Ph.D.      Peter Tarr, Ph.D.
Jonathan D. Cohen, M.D., Ph.D.    Robert M. Kessler, M.D.            Elaine Sanders-Bush, Ph.D.
Richard Coppola, D.Sc.            Kenneth K. Kidd, Ph.D.             Alan F. Schatzberg, M.D.                EDITORS:
Joseph T. Coyle, M.D.             Mary-Claire King, Ph.D.            Nina R. Schooler, Ph.D.                 Laura Wells
Jacqueline Crawley, Ph.D.         Rachel G. Klein, Ph.D.             Robert Schwarcz, Ph.D.                  Vice President of Marketing
Karl Deisseroth, M.D., Ph.D.      John H. Krystal, M.D.              Philip Seeman, M.D., Ph.D.              and Communications
J. Raymond DePaulo, Jr., M.D.     James F. Leckman, M.D.             Solomon H. Snyder, M.D., Ph.D., D.Sc.
Ariel Y. Deutch, Ph.D.            Robert H. Lenox, M.D.              John S. Strauss, M.D.                   Barbara Wheeler
Wayne C. Drevets, M.D.            David A. Lewis, M.D.               John A. Talbott, M.D.                   Manager of Communications
Ronald S. Duman, Ph.D.            Jeffrey A. Lieberman, M.D.         Carol A. Tamminga, M.D.                 and Media Relations
Jan A. Fawcett, M.D.              Irwin Lucki, Ph.D.                 Laurence H. Tecott, M.D., Ph.D.
Judith M. Ford, Ph.D.             Robert C. Malenka, M.D., Ph.D.     Ming T. Tsuang, M.D., Ph.D.             LAYOUT/DESIGN:
Alan Frazer, Ph.D.                Husseini K. Manji, M.D.            Leslie G. Ungerleider, Ph.D.            Lorraine Divone
Robert R. Freedman, M.D.          J. John Mann, M.D.                 Nora D.Volkow, M.D.                     Production and Art Director
Fred H. Gage, Ph.D.               John S. March, M.D., M.P.H.        Karen Dineen Wagner, M.D., Ph.D.
Mark S. George, M.D.              Helen S. Mayberg, M.D.             Daniel R. Weinberger, M.D.              Cover:
Elliot S. Gershon, M.D.           Robert W. McCarley, M.D.           Jon-Kar Zubieta, M.D.                   J. Randolph Lewis,
Mark A. Geyer, Ph.D.              Bruce S. McEwen, Ph.D.                                                     Walgreen Co.
                                           Introducing our special issue on
                                           ‘New Hope in Mental Health’




When I was asked to write an introductory comment for this          Welcome to the first issue of The Quarterly to include our new
edition of the Brain & Behavior Research Foundation Quar-           name and logo! We are now the Brain & Behavior Research
terly with its theme “New Hope in Mental Health,” I thought         Foundation – still committed to alleviating the suffering of
of how much we have gone beyond hope. All we had was a              mental illness by awarding grants that will lead to advances
tiny handful of drugs to offer patients with mental illness         and breakthroughs in scientific research.
when we started the National Alliance for Research on Schiz-
ophrenia and Depression (NARSAD), which has now become              In this special edition of The Quarterly, we look across the land-
the Brain & Behavior Research Foundation.We started as a            scape of mental health and bring you a set of perspectives from
group of psychiatrists, psychologists, neuroscientists and others   diverse sources on how much progress has been made.We call
planning to work together to build and support the scientific       it “New Hope in Mental Health” because as we spoke with
research efforts to address the challenges of mental illness. In    each leader – representing the public, private and nonprofit
that first year, we selected and funded 10 young scientists. In     sectors, and also scientific and family perspectives – we heard
the ensuing 24 years, our effort has now funded research by         messages of great accomplishments, instilling confidence that
more than 3,300 scientists worldwide.                               the challenges still to be met can be successfully achieved with
                                                                    innovative approaches.We believe that by joining forces, and
The small group of 24 who pioneered this research program           working in partnerships across sectors, we can offer the
as the NARSAD Scientific Council has now grown to include           chance for the mentally ill to live full, productive lives.
124 volunteer members, each of whom bring special skills
and unique knowledge bases that cover every aspect of brain         From understanding the malfunctions in the brain that lead to
and behavior research.The reach of NARSAD, and now the              brain and behavior disorders, to treating symptoms and retrain-
Brain & Behavior Research Foundation, support extends               ing the brain, to ultimately supporting rehabilitation efforts
to the world's leading medical research and care facilities.        that enable full, productive lives – all this is the cause we sup-
Our effort knows no borders. The impact of our effort is            port. And through your continued generosity, we will con-
not only in the development of promising scientists, but            tinue to fund efforts in each of these stages to Recovery through
also in the focus it brings to the challenge and urgent need        our grants. Please join with us in accelerating our Campaign
of bringing hope and better lives to all those living with          for Productive Lives that is introduced on pages 10-11.Your
mental illness.                                                     added support has never been more critical – and the hope
                                                                    has never been more justified.
The articles in this publication demonstrate the power of new
ideas when they are supported and given the opportunity to          Please help expand the network of partners in this effort. Share
develop into tangible treatments and programs. I expect you         this special issue with your family and friends. Together, we
will also feel the New Hope we now have and appreciate the          can meet the challenges and offer the reality of productive
necessity of continuing to forge forward in our efforts.            living to all those who still suffer.

Sincerely,                                                          Sincerely,



Herbert Pardes, M.D.                                                Benita Shobe
President, Brain & Behavior Research Foundation                     President and CEO
Scientific Council                                                  Brain & Behavior Research Foundation


                                                                                             www.bbrfoundation.org             1
   Research Discoveries in the News



  Research Discoveries
                                                    in the News

                                             Research Suggests Why and How Women
                                             Are More Vulnerable to PTSD
Kerry J. Ressler, M.D., Ph.D.



   Kerry J. Ressler, M.D., Ph.D., mem-       associated with the PACAP system.        may arrive at PTSD by different bio-
   ber of the Brain & Behavior Research      (SNPs, pronounced “snips,” are varia-    logical pathways, and that now re-
   Foundation Scientific Council, led        tions in the DNA sequence in a gene.)    searchers have a clue as to how that
   recent research that may demonstrate      They found that a variation in the       works – the genetic data that points
   one reason why women are generally        gene for the PACAP receptor, which       to changes in the ability to respond
   more vulnerable to post-traumatic         appears to change how that gene re-      to estrogen.
   stress disorder (PTSD) than men and       sponds to the primary female hor-
   pinpointed a genetic anomaly that         mone estrogen, was linked to PTSD        Pointing to these results as opening a
   could account for the disparity.          risk in women.                           new window into the biology of
                                                                                      PTSD, Dr. Ressler expresses the hope
   In an initial study of 64 subjects with   However, despite comparable levels of    that the identification of PACAP as
   a history of significant trauma, Dr.      trauma, women in the study with the      an indicator of PTSD may lead to
   Ressler and his team found that a         more protective PACAP receptor gene      new diagnostic tools and eventually
   high blood level of a hormone called      variation had lower rates of PTSD than   to new, more precisely targeted treat-
   PACAP (pituitary adenylate cyclase-       men, as opposed to those women with      ments for anxiety disorders.
   activating polypeptide) in women          the risk gene variation.
   but not in men was associated with                                                 Dr. Ressler is a Howard Hughes Medi-
   women’s higher incidence of PTSD.         PACAP has long been known to be a        cal Institute Investigator and an asso-
   In addition to the differences observed   stress-response hormone, but its spe-    ciate professor in the department of
   between the sexes, the research also      cific role in PTSD has been unclear.     psychiatry and behavioral sciences in
   showed that women with above-aver-        The study’s findings, which were re-     the Emory University School of
   age PACAP levels had PTSD symp-           ported in the Feb. 24 issue of the       Medicine, and a researcher with the
   tom scores five times higher than         journal Nature, suggest strongly to      Yerkes National Primate Research
   women with lower PACAP levels.            Dr. Ressler and his colleagues that      Center in Atlanta. Dr. Ressler re-
                                             PACAP and its receptor system may        ceived 2002 and 2005 NARSAD
   To explore the basis of these findings,   be integrally involved in regulating     Young Investigator Grants and was
   the team conducted genetic studies        the psychological and physiological      honored with a 2009 NARSAD
   in more than 1,200 traumatized sub-       responses to traumatic stress. The re-   Freedman Award recognizing his sig-
   jects, examining 44 single nucleotide     search also seems to indicate that men   nificant findings as a Young Investi-
   polymorphisms, or SNPS, of genes          and women who have been traumatized      gator grantee. O


   2 The Quarterly
                                                                        Research Discoveries in the News




Surprising Discovery of an Anxiety-Reducing
Circuit Within the Brain’s ‘Fear’ Center
                                                                                                        Karl Deisseroth, M.D., Ph.D.



Brain & Behavior Research Founda-            scientists can switch individual neurons     the same amygdala circuit, the mice
tion Scientific Council Member Karl          and specific neural pathways “on” and        instantly began to manifest anxious
Deisseroth, M.D., Ph.D., of Stanford         “off ” at will.                              behaviors.
University, has conducted a series of
experiments to more precisely tease          In a newly published paper, Dr. Deis-        It has been estimated by the National
out neural circuits inside the amygdala      seroth’s team describes using optoge-        Institute of Mental Health that more
under the thesis that knowing more           netics to target a specific circuit in the   than 1 in 4 Americans (28%) will suffer
about them could lead to better ther-        mouse’s amygdala – which is quite            a clinically important anxiety-related
apeutic solutions for excessive fear and     similar to its human counterpart. For        condition over the course of their life-
anxiety. Most existing anti-anxiety          many years scientists have understood        time. Therefore, finding a specific
drugs are only partly effective, and         that the amygdala is important in the        amygdala circuit that can be stimu-
some have significant side effects. Dr.      processing of certain kinds of emo-          lated to reduce anxiety is important:
Deisseroth used a cutting-edge method        tional responses, among them fear. It        it could affect the development of
he invented with the help of his 2005        is also commonly assumed that some-          improved treatments.
NARSAD Young Investigator Grant              thing in the amygdala is amiss in peo-
called optogenetics in his study.            ple who suffer from anxiety disorders.       Dr. Deisseroth says the study under-
                                             But what, exactly, and how can this be       lines the importance of tracing and
In developing optogenetics, Dr. Deis-        most effectively addressed?                  understanding the functional dynam-
seroth discovered a way of using beams                                                    ics of specific pathways within brain
of colored light to activate specific        While the amygdala has usually been          structures, in the continuing effort to
types of nerve cells in the brains of liv-   associated with the “fear” response, Dr.     find out the specific causation of psy-
ing mice.This remarkable technology          Deisseroth’s team showed that stimu-         chiatric illness. O
is based on a genetic “trick”: breeding      lation of a specifically targeted circuit
strains of mice whose nerve cells are        actually made the mice rather bold –
photosensitive.When light of a partic-       in other words, the very opposite of
ular wavelength is carried along a thin      anxious.“The effect was instantaneous
fiber optic wire into such an animal’s       and could be seen as soon as the light
brain – something that can be done           was switched on,” Dr. Deisseroth says.
painlessly and does not restrict the         Conversely, when the team used a dif-
animal from moving about freely –            ferent wavelength of light to inhibit


                                                                                               www.bbrfoundation.org            3
Research Discoveries in the News




                                             Foundation-Funded Discovery of New
                                             Schizophrenia Gene Could Lead To New
                                             Diagnostic and Therapy Possibilities
Jonathan Sebat, Ph.D.


Within the last several years, scientists,   The gene, called VIPR2, encodes a             Although the mechanism of how
a number of them working with                receptor expressed in important brain         such overexpression might con-
NARSAD Grants, have capitalized on           areas including the hippocampus (con-         tribute to the onset of schizophrenia
the discovery that some people with          nected to learning and memory),               is still not known, that will surely be
schizophrenia and other brain and            amygdala (connected to fear and other         a subject of ongoing studies.
behavior disorders have extra or miss-       emotions) and suprachiasmatic nucleus
ing sections in their genomes – sec-         (regulator of day/night cycles).              Additionally, Dr. Sebat said, the dis-
tions which sometimes correlate with                                                       covery points to a potentially impor-
the location of genes known from             Some CNVs cover comparatively large           tant new schizophrenia drug target.
previous studies to be associated with       chunks of the genome, in which sev-           “A drug that selectively blocks that
heightened risk for these illnesses.         eral or many genes are found. In such         receptor could have therapeutic po-
                                             instances, it is difficult to discern which   tential in patients who have the
Brain & Behavior Research Founda-            gene is important. The new region             VIPR2 mutation,” Dr. Sebat says.
tion Grantee Jonathan Sebat, Ph.D.,          identified by Dr. Sebat and colleagues
of the University of California, San         is on chromosome 7. Many of the               “This is the kind of gene that drug
Diego, is one of the pioneers in find-       duplications in this region impacted          developers have been waiting for,” Dr.
ing these extra and missing genome           just one gene – VIPR2. The VIPR2              Sebat says. “Molecules have already
areas, which are called copy-number          gene encodes a receptor that binds to         been created that are known to mod-
variations, or CNVs. In a new study          a neuropeptide hormone and trans-             ulate VPAC2. This is what genomic
published in March, a large interna-         mitter called “VIP.”                          medicine is all about: finding the rel-
tional team led by Dr. Sebat and in-                                                       evant genes and using this informa-
cluding Foundation Grantees Mary-            “The link between VIPR2 duplica-              tion to inform the development of
Claire King, Deborah L. Levy, and            tions and schizophrenia may have sig-         new treatments.”
Elliot S. Gershon announced the dis-         nificant implications for the develop-
covery of a new gene that evidence           ment of molecular diagnostics and             In 2010, Dr. Sebat was a recipient of
shows to be mutated in a small but           treatments,” Dr. Sebat notes. “For ex-        a NARSAD Independent Investiga-
significant subset of schizophrenia          ample, genetic testing for this duplica-      tor Grant.O
patients. Those who carry the muta-          tion could enable early detection of a
tion have greatly elevated risk for the      subtype of patients who have over-
disease – some 14 times the risk of          expression of the VIPR2 gene.”
those who don’t have it.

4 The Quarterly
                                                                           Interview with a Researcher



Interview
  with     Bryan L. Roth, M.D., Ph.D.
           Scientific Council Member
           Michael Hooker Distinguished Professor
           Department of Pharmacology, School of Medicine
           Department of Medicinal Chemistry
                     and Natural Products, School of Pharmacy
           Director, NIMH Psychoactive Drug Screening Program
           University of North Carolina Chapel Hill Medical School




A Personal Connection
Launches Brilliant Career
Twenty-year career leading discoveries into the complex
circuitry of the brain points toward more effective treatments

Having personally encountered mental      didn’t even have a psychiatrist. My       National Institute of Mental Health
illness in his own family, Bryan L.       relative with schizophrenia had to be     (NIMH), which is run by his lab.
Roth, M.D., Ph.D., member of the          sent away, for a long period, to the
Brain & Behavior Research Founda-         Warm Springs State Hospital, which        Dr. Roth’s motivating family experi-
tion Scientific Council, has worked       was some distance from where we           ences coincided with his natural gifts
throughout his career to find better      lived. That had a huge effect on me.”     in biology and chemistry, which be-
treatments for people living with                                                   came evident in his early school years.
brain and behavior disorders.             Dr. Roth is one of the nation’s leading   From his first exposure in college to
                                          experts in pharmacology and psychi-       how nerve cells in the brain commu-
“From a very young age, I’ve been         atric drug development, a biochemist      nicate, he became convinced “that this
exposed to the devastation caused by      whose work since the early 1990s has      is where the important answers to
serious mental illness,” Dr. Roth says.   earned him all three classes of           mental illness would eventually come
“When I was a child, I had a close        NARSAD Grants – a Young Investi-          from.” He earned M.D. and Ph.D.
family member who had schizophre-         gator Grant in 1992, an Independent       degrees at St. Louis University Medical
nia. I also had a close relative who      Investigator Grant in 1998, and most      School, and after postdoctoral research
took her own life because of recur-       recently a Distinguished Investigator     at the NIMH, Dr. Roth went on to a
rent bipolar disorder.”                   Grant, in 2008. Now the Michael           psychiatric residency at Stanford Uni-
                                          Hooker Distinguished Professor of         versity Medical Center. His mentor
This deeply sensitized Dr. Roth, a re-    Pharmacology at the University of         there, Dr. Roland Ciranello, was an
action perhaps even more pronounced       North Carolina School of Medicine,        early member of the Brain & Behavior
as a consequence of geography. “I’m       he is also director of the Psychoac-      Research Foundation (then NARSAD)
from a town in Montana so small it        tive Drug Screening Program of the        Scientific Council, as was the researcher



                                                                                        www.bbrfoundation.org              5
Interview with a Researcher


Without Brain & Behavior Research Foundation “there                                      All of these hard-to-answer questions
                                                                                         might reduce to this ultimate one:
was no way my early work could have gotten off the
                                                                                         How do scientists develop psychiatric
ground. They gave me resources when I didn’t have any.”                                  drugs that work better for more pa-
                                                                                         tients, with an absolute minimum of
who recruited him for his first aca-       that first grant yielded a number of          side effects?
demic appointment at Case Western          “my most highly cited scientific papers,
Reserve University: Dr. Herbert            which still hold up pretty well today,        ‘Silver bullets’
Meltzer, a pioneer in the develop-         I’m pleased to say.” These papers are         vs. ‘magic shotguns’
ment of the second generation, or          about the way atypical antipsychotic          The discoveries that have come out of
“atypical,” antipsychotic medications.     drugs such as clozapine produce their         Dr. Roth’s lab over two decades (see
                                           effects, a subject that continues to be       sidebar) call attention to a major debate
NARSAD Grants were critical                important not only for Dr. Roth but           that has deeply influenced many teams
support                                    for the entire psychiatric community.         of drug developers. Using clozapine
These mentoring relationships of Dr.                                                     as a case in point, Dr. Roth explains:
Roth’s reflect the way the Brain &         Discoveries about a drug’s mechanism          “An idea arose, when we discovered
Behavior Research Foundation has           of action are vital. Knowing exactly          in the ’90s how many different tar-
shaped the development of the men-         how a drug affects the biology and            gets the drug hits, that one of those
tal health research field. From its ear-   chemistry of the body, and particular-        targets was going to be the key that
liest days, it has supported scientists    ly the part of the body where it gener-       accounts for the drug’s positive effects”
that have come to be the leaders in        ates its therapeutic effects, is crucial.     – and that if it could be isolated, the
psychiatry and neuroscience and who                                                      drug could be re-engineered to hit
have, in turn, served on the organi-       Dr. Roth and colleagues have learned          just that target and no others, thus
zation’s Scientific Council. The Sci-      that clozapine interacts with at least 73     minimizing side effects.
entific Council reviews all grant          different protein “targets” in the brain.
applications, selecting the most           The development of the science that           The idea of such a drug – a “silver
promising ideas and eventually men-        makes possible tracking and identifying       bullet” – “seemed reasonable at the
toring the chosen grantees.                all of these targets is itself an important   time,” Dr. Roth says. “But in retro-
                                           achievement. Beyond this, the discov-         spect, it has proved naïve. We now
Dr. Meltzer not only recruited Dr.         ery of clozapine’s many interactions          know that illnesses like schizophrenia
Roth, but urged him to apply for a         raises all sorts of questions, which have     are so much more complex than we
NARSAD Young Investigator Grant.           provided new points of departure for          ever imagined.” The game-changer
It was great advice, Dr. Roth says, for    Drs. Roth, Meltzer and many others.           was the Human Genome Project and
at the time – around 1991 – “I was just                                                  the remarkable technologies it has
starting out in my own lab at Case         The nub of the issue is this: if a drug       spawned, which have made possible
Western, and grants were very hard         affects 73 different targets, then which      the discovery of potentially hundreds
to come by, even more so than today.       of these account for the benefits it          of genetic causes of complex illnesses
The government was rejecting 95            brings patients? Which targets are spe-       like schizophrenia.
out of every 100 grant applications,       cifically associated with which positive
which meant a lot of worthy science        effects? Which targets in particular can      The pharmaceutical industry spent a
was not being funded.”                     be associated with specific side effects?     great deal of time and money searching
                                                                                         in vain for psychiatric silver bullets.
Without the Brain & Behavior Re-           Adding another layer of complexity:           But this is how scientific knowledge
search Foundation “there was no way        How do the answers to the above               is gained – experiments are conducted,
my early work could have gotten off        questions vary in different patients?         the outcome of which can’t be known
the ground. And that’s the whole           Can they explain why certain patients         in advance. Dr. Roth accentuates the
purpose of NARSAD Grants,” Dr.             are helped more by a given drug than          positive implications: while the idea
Roth says. “They gave me resources         other patients? Why some derive lit-          of single-target therapies did not pan
when I didn’t have any.” In fact, Dr.      tle or no benefit? Why some suffer            out in the area of psychiatric medica-
Roth says, the work supported by           certain side effects and others don’t?        tions – partly reflecting the complexity


6 The Quarterly
Dr. Roth is pictured at a robotic-based small molecule screening facility where hundreds of thousands of drug-like compounds are evaluated.
This work plays a role in discovering new treatments for serious mental illnesses.The facility is located within the NIMH Drug Screening
Program under the direction of Dr. Roth at University of North Carolina.

of the brain – it has proven a valuable         highly selective drugs,” he says, “and         No one has to tell Bryan Roth about
approach in cancer drug development.            we’ll find subsets of patients who will        the urgency of finding better drugs.
But even in psychiatry, the data have           respond to these, but that population          “My relative with schizophrenia
clearly identified many targets that do         is likely to be small in each case.”           lived as a street person on and off for
account for serious side effects, and                                                          25 years, refusing to take medicine
these have indicated various ways to            How, then, to go forward? Dr. Roth             because of the debilitating side ef-
make existing drugs more tolerable              believes the magic shotguns could              fects,” he says. “When we finally got
for more patients.                              provide the greatest benefit for the           her on one of the newer ‘atypical’
                                                greatest number of psychiatric patients        medications, it absolutely transformed
Just as important, the data on multi-           due to the complexity of brain chem-           her life.” Poignantly, she invariably
ple targets points to what effective            istry. The specific hope, in schizo-           asks him, in their frequent phone chats,
psychiatric drugs do in the brain. It’s         phrenia, “is that genetic data will            “Have you learned anything new
probable, Dr. Roth says, that drugs             reveal neural circuits involved in the         about schizophrenia today, Bryan?”
like clozapine derive much of their             illness, and that we will learn how to
therapeutic benefit precisely because           modulate these neurocircuits with              With the continued investment from
they hit multiple targets. He calls the         drugs. The idea is that we can test            the Brain & Behavior Research Foun-
lesson from this the “magic shotgun”            ideas we have about which neural               dation in innovative ideas and prom-
approach to drug development, refer-            circuits are important for various dis-        ising scientists, Dr. Roth is confident
ring to a shotgun’s propensity to “spray”       eases. That’s where technologies have          that he and other scientists will con-
its fire over a wider area than a single        really opened new doors” (see sidebar).        tinue to answer, “Yes.”O
bullet. “We can certainly develop


                                                                                                    www.bbrfoundation.org                7
Interview with a Researcher



                                  Leading Researcher Uses Innovative Ways
                                  To Improve Treatments
                                  “What’s most hopeful about our field today is the fact that we have the tech-
                                  nologies in hand that will get the answers to mental illness in ways never be-
                                  fore possible,” says Bryan Roth, M.D., Ph.D., and member of the Brain &
                                  Behavior Research Foundation Scientific Council. “We’re going to know all
                                  the genes involved, and the circuits that regulate complex behaviors. And from
                                  the intersection of those two areas, I believe new treatments will become
                                  obvious.The insights we obtain will lead to discoveries that will transform the
                                  lives of people with these illnesses.”

                                  Dr. Roth speaks from the perspective of one who spends long hours in the lab,
                                  conducting research on how to design more effective drugs, based in part on
                                  technologies that he and his protégés have invented. NARSAD Grants have
                                  helped support new projects conceived by some of the lab’s most promising
                                  doctoral students.

    One technology invented by Dr. Roth and colleagues, based on Dr. Roth’s 2008 NARSAD Distinguished
    Investigator Grant, goes by the acronym DREADD, for Designer Receptors Exclusively Activated by Designer
    Drugs. These manmade receptor molecules can be genetically introduced into any cell in mice, which are
    used to model human illnesses.The DREADDs enable scientists to switch “on” and “off ” specifically selected
    nerve cells in the brain. In this sense, DREADDs are akin to a revolutionary method devised by another
    Brain & Behavior Research Foundation Scientific Council Member, Dr. Karl Deisseroth, whose “optogenetics”
    technology enables researchers to activate and deactivate specific neurons with beams of colored light.

    Dr. Roth’s DREADDs – which his lab has synthesized and bred into a line of mice, now available to re-
    searchers worldwide – provide a means of determining precisely which effects of a drug to attribute to the
    drug’s action on its intended target(s), and which (if any) are generated by so-called “off-target effects,” i.e.,
    impacts on parts of the cell or neural circuitry that are not expected. Using DREADDs, Dr. Roth’s team
    recently reported success in teasing out the details of neural circuitry that had long eluded scientists’ best
    efforts – one that connects several brain regions involved in the biology of addiction.

    Another of the lab’s major efforts addresses the problem of how to optimally design drugs that hit multiple
    targets – the “shotgun approach.” In designing a drug to hit a single target, it’s relatively simple to set up
    screens that will show which molecules adhere best to the target. Multiple-target drugs present a much
    deeper challenge, since rational design implies biological knowledge of interactions among multiple parts
    of one or more neural circuits. The Roth team’s approach turns the traditional drug discovery process on
    its head.

    “Rather than screen every proposed drug molecule against every known target, we asked, ‘Is there a way
    to predict the target?’ With some colleagues, including my longtime collaborator Brian Shoichet at UCSF
    and his brilliant student Michael Keiser, we came up with computer programs that explore possible drug
    interactions mathematically.” It’s part of a field called chemo-informatics, and what excites Dr. Roth is that
    with it his team was able in a 2009 demonstration to sift 3,665 known drugs against hundreds of known
    targets and identify many interactions that no one had ever seen or anticipated. Even better, he said, the team
    actually validated 23 of these experimentally, and one was successfully tested in a mouse model. O




8 The Quarterly
                                                                                                 Ask the Researcher


Answers to Ask the Researcher
from John H. Krystal, M.D.
            Scientific Council Member
            Chair, Department of Psychiatry, Yale University
I was diagnosed as having early stage Alzheimer’s                  need for medication
disease. Has neuroplasticity research touched on the               treatments or changes
possibility of brain adaptation and new learning for               in these medications
Alzheimer’s patients? Could my brain be retrained                  to better control
by rote memory exercises or some other learning                    these symptoms.
method of adaptation?
This is an important question.Alzheimer’s disease is an illness    How can a doctor or counselor help me feel less
where there remains an important unmet need in relation to         afraid or tense?
preserving or enhancing cognitive function.While this is not       Many people are troubled by thoughts and feelings that they do
my area of research, I am aware of efforts to develop cognitive    not feel comfortable sharing with their friends or family mem-
training therapies for Alzheimer’s disease that have produced      bers. The inability to share these thoughts and feelings can
some limited benefits in pilot studies. It would be interest-      make people feel isolated, unsupported and ashamed. Mental
ing to know whether the standard medication treatments             health professionals are specifically trained to help people feel
for Alzheimer’s disease, such as memantine or cholinesterase       comfortable in sharing their difficult thoughts and feelings
inhibitors, both of which increase some forms of neuro-            and to provide feedback and sometimes homework exer-
plasticity, alter the impact of cognitive training. D-cy-          cises that help many people feel better afterwards. Overall,
closerine has been explored as a medication to treat memory        people who have problems with tension and anxiety that are
impairments for people with this disorder and most stud-           interfering with their life find it helpful to talk to a therapist.
ies of this medication have been negative. I am not aware,
though, of studies that have specifically tried to enhance the     How long does PTSD last?
impact of memory training by adding D-cycloserine.                 Length of time varies. According to our diagnostic manual,
                                                                   one must have symptoms for at least one month following
This year will mark the 10th anniversary of the                    an event to receive a PTSD diagnosis. In some cases, particu-
September 11, 2001 terrorist attacks in the United                 larly where it is not treated, PTSD can last a very long time,
States and I dread watching the media review the                   perhaps the remainder of one’s life. Most people with long-
events of this day. With continued traumatic events,               standing PTSD find that the symptoms are not steady in their
such as the recent tsunamis, Katrina/Rita, Haiti earth-            severity. For some people, the symptoms gradually fade over
quake, Gulf Oil Spill, what are your recommenda-                                         time. Other people find that symptoms
tions on how to manage this type of stress?                                                   may increase when they encounter
It is true that we seem to be bombarded with news related          Ask the                     reminders of their traumatic events.
to disasters and social upheaval from around the world.What        Researcher Anniversaries of the event, for ex-
is remarkable is the capacity of most people to be resilient                                 ample, are commonly difficult times.
to the impact of this bad news most of the time. People
with a history of problems related to post-traumatic stress        Please e-mail asktheresearcher@bbrfoundation.org with
disorder (PTSD), depression or other psychiatric disorders         questions for Dr. Bryan Roth. Select questions and answers will
may be more sensitive to the bad news, particularly when           be published in the next issue of The Quarterly.
they are feeling poorly. The most commonly used strategy           This column is intended to give you the opportunity to ask ques-
at these difficult times is to get together with friends and       tions of the researcher profiled in “Interview with a Researcher”
family members to take advantage of the opportunities that         and give us the opportunity to bring our mission to life.
we have to support each other.When the usual sources of            Please note that this column is intended to provide answers to
support do not seem adequate, counseling or therapy can            questions related to scientific research and discoveries lead-
                                                                   ing to better treatment of a broad range of mental illnesses.
be helpful. Sometimes, significant worsening of symptoms           The researcher cannot give specific recommendations or ad-
in the context of PTSD, depression or other illnesses is a         vice about treatment; diagnosis and treatment are complex
sign that medication treatments for these problems are not         and highly individualized processes that require comprehen-
                                                                   sive face-to-face assessment. This Q&A forum is not meant to
adequately effective. In this context, it can be helpful to meet   serve as a substitute for that, but rather to share insights.
with your therapist, doctor or psychiatrist to evaluate the

                                                                                               www.bbrfoundation.org                9
                     Campaign for Productive Lives

                     Our Campaign for Productive Lives

                                          Accelerate the breakthroughs with
                                          $200 million in new support over 5 years

                                 Supporting Breakthroughs with Annual NARSAD Grants
                                               Amount of NARSAD Grant Funding per year
                     $500
                     $450
                     $400
In Million Dollars




                     $350
                     $300
                     $250
                                                                                                                   200
                     $200                                                                                    al: $
                                                                                                          Go llion
                     $150                                                                                    mi nal
                                                                                                                itio
                     $100                                                                                  a dd ars
                                                                                                                 ye
                      $50                                                                                  in5
                       $0
                              87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06 07 08 09 10 11 12 13 14 15
                            19 19 19 19 19 19 19 19 19 19 19 19 19 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20




                     What will $200 million achieve?

                        •   $120 million additional funding for Young Investigators
                            o Increase grant amount from $60,000 to $90,000 over two years
                            o Grants are awarded to the most promising young scientists


                        •   $50 million additional funding for Independent Investigators
                            o Grants are awarded to researchers during the critical period between initiation
                               of research and receipt of sustained funding

                        •   $30 million additional funding for Distinguished Investigators
                            o Grants are used to fund a particularly talented, established investigator



                     10 The Quarterly
                                                              Campaign for Productive Lives


                                “The Brain & Behavior Research Foundation is unrivaled in its innovative
                                and expert approach to funding the most promising ideas in brain and
                                behavior research. Its funding decisions are steered by the best scientists
                                in the field and the reserch sponsored has consistently led to important
                                advances.”

                                Eric R. Kandel, M.D., Nobel Prize Winner
                                Columbia University University Professor; Fred Kavli Professor
                                and Director, Kavli Institute for Brain Science,
                                Scientific Council Member



“NARSAD Grants are essential to the field of brain and behavior
research. They encourage the best scientists to enter and stay in
the field, and fund the most promising paths toward discoveries
that increase our understanding of these illnesses, ultimately leading
to better treatments for all those affected.”

Paul Greengard, Ph.D., Nobel Prize Winner
The Rockefeller University, Vincent Astor Professor
of Molecular and Cellular Neuroscience,
Scientific Council Member




Why Our Campaign Is Critical
• 1 in 4 Americans experiences a brain                   • Discoveries set the pace for research
  and behavior disorder each year.                         leading to breakthroughs
   (National Institute of Mental Health 2010)

• Direct and indirect components of                      • Scientists see the threshold of a new
  the economic burden of serious brain                     era in psychiatry, yet face reductions
  and behavior disorders…exceed                            in funding for mental health research
  $300 billion annually.                                   on the national level.
   (Insel, American Journal of Psychiatry 2008)



 The Brain & Behavior Research Foundation can only fill this gap and keep the
 momentum going with your support of the Campaign for Productive Lives.

 Be a part of breakthrough research to find the answers and improve the lives of all
 those living with mental illness today.


                                                                            www.bbrfoundation.org       11
FAQs




?
Frequently Asked
                   Questions
                   on Mental Health
                     Q   How common is mental illness?

                         Brain and behavior disorders are common in the United
                         States and internationally. An estimated 26.2 percent of


                     A
                         Americans ages 18 and older – about 1 in 4 adults – suffer
                         from one or more of these disorders in a given year. Brain
                         and behavior disorders are common among children in the
                         United States and are increasingly being recognized and
                         diagnosed at an early age. Just over 20 percent (or 1 in 5)
                         children live with a debilitating mental illness.
                         (Source: National Institute of Mental Health (NIMH))



                     Q   What are the most frequent types?

                         Out of the 10 leading causes of disability identified and
                         tracked in the United States and other developed countries,


                     A   four are brain and behavior disorders: major depression,
                         bipolar disorder, schizophrenia and obsessive-compulsive
                         disorder.

                         It is estimated that:
                         • 18.1% of American adults will suffer from an anxiety
                            disorder each year
                         • 6.7% of Americans will suffer from major depressive
                            disorder each year
                         • 4.1% of American adults will suffer from attention-
                            deficit/hyperactivity disorder each year
                         • 3.5% of American adults will suffer from post-traumatic
                            stress disorder each year
                         • 2.6% of American adults will suffer from bipolar
                            disorder each year
                         • 1.1% of American adults will suffer from schizophrenia
                            each year
                         • 1% of American adults will suffer from obsessive-
                            compulsive disorder each year
                         • 1 in every 110 8-year-old children are diagnosed with
                            an autism spectrum disorder (Source: Autism and Develop-
                            mental Disabilities Monitoring (ADDM) Network, 2006)
                         (Source: NIMH)
12 The Quarterly
                                                                                               FAQs



Q   How are mental health problems
    diagnosed in young children?

    Just like adults, children with mental illness
                                                           • Growing inability to cope with daily
                                                             problems and activities
                                                           • Suicidal thoughts
                                                           • Denial of obvious problems
                                                           • Numerous unexplained physical ailments


A
    are diagnosed after a doctor or mental
                                                           • Substance abuse
    health specialist carefully observes signs and
    symptoms. Some primary care physicians
                                                           Early warning signs and symptoms in older
    can diagnose children, but most will make a
                                                           children and pre-adolescents include:
    referral to a specialist who is better trained
                                                           • Substance abuse
    in diagnosing and treating children. Before
                                                           • Inability to cope with problems and daily
    diagnosing a mental illness, the doctor or
                                                              activities
    specialist will try to rule out other possibili-
                                                           • Changes in sleeping and/or eating habits
    ties for the symptoms or behaviors causing
                                                           • Excessive complaints of physical ailments
    concern. Generally, the process involves:
                                                           • Defiance of authority, truancy, theft
                                                              and/or vandalism
    • Evaluating the familial history of any
                                                           • Intense fear of weight gain
      important medical problems, including
                                                           • Prolonged negative mood, often
      any brain and behavior disorders.
                                                              accompanied by poor appetite or
    • Tracking the development of current
                                                              thoughts of death
      concerns – how long have the symptoms
                                                           • Frequent outbursts of anger
      or behaviors been an issue; how is the
      overall development of the child; etc.
                                                           Early warning signs and symptoms in younger
    • Creating a personal history for the child:
                                                           children include:
      e.g., if any physical or psychological
                                                           • Changes in school performance
      traumas have been experienced; are there
                                                           • Poor grades despite strong efforts
      any issues at school or with socializing.
                                                           • Excessive worry or anxiety (i.e., refusing
      This history may include input from
                                                              to go to bed or school)
      parents, teachers, other caretakers.
                                                           • Hyperactivity
    • In the United State, brain and behavior
                                                           • Persistent nightmares
      disorders are diagnosed based on the
                                                           • Persistent disobedience or aggression
      Diagnostic and Statistical Manual of
                                                           • Frequent temper tantrums
      Mental Disorders, fourth edition
                                                           (Source: Mental Health America)
      (DSM-IV). (Source: NIMH)



Q
    Are there early warns signs to look
    out for before the illnesses reach a
    critical state?
                                                       Q   Where can I find mental health
                                                           resources in my community?

                                                           The Substance Abuse and Mental Health
                                                           Services Administration (SAMHSA) offers
    Early warning signs and symptoms in adults
                                                           a services locator for mental health and


A
    include:

                                                       A
                                                           substance abuse treatment programs and
    • Confused thinking
                                                           resources nationwide.
    • Prolonged depression (sadness
                                                           Call 1-800-950-6264 and select option #2
       or irritability)
                                                           or visit store.samhsa.gov/mhlocator.
    • Feelings of extreme highs and lows
                                                           To learn more about insurance coverage
    • Excessive fears, worries and anxieties
                                                           for mental health services and for questions
    • Social withdrawal
                                                           concerning Social Security Income Disabil-
    • Dramatic changes in eating or sleeping
                                                           ity issues or Supplemental Security call
       habits
                                                           1-800-772-1213.
    • Strong feelings of anger
    • Delusions or hallucinations


                                                                      www.bbrfoundation.org           13
      Research Partners
       A Personal Connection
           The Power of Partnership
         Between Donor and Researcher

                  Luisa Francoeur sponsors Dr. Angus
                  MacDonald and the line of research that
                  has made a difference to her son.

                  “We do this for our son’s sake but also thinking
                  of the millions of others – the sick and their loved
                  ones – who are going through similar experiences.”




 • Select and support a scientist in your area of interest, an institution
   or geographic area

 • Receive progress reports

 • Develop personal relationships and heightened insights
   to breakthroughs on the horizon

 • Be recognized in all published work resulting from the research



Become a Research Partner and sponsor breakthroughs today!

                For information call (516) 829-0091
N ew
Hope
   in Mental
      HEALTH
       16   PUBLIC SECTOR PERSPECTIVE
            Thomas Insel, M.D., Director, NIMH

       19   PRIVATE SECTOR PERSPECTIVE
            J. Randolph Lewis, Senior VP, Walgreen Co.

       22   RESEARCH PERSPECTIVE
            Carol A. Tamminga, M.D., Member,
            Brain & Behavior Research Foundation
            Scientific Council

       24   FAMILY PERSPECTIVE
            Constance E. Lieber, President Emerita,
            Brain & Behavior Research Foundation

       26   NONPROFIT SECTOR PERSPECTIVE
            Kenn Dudek, President, Fountain House
New Hope in Mental Health




                                            ‘The Same Was True for Cancer
                                            10 or 15 Years Ago’
                                             Dr. Thomas Insel, director of the
                                             National Institute of Mental Health,
                                             shares his view on the current landscape
                                             of mental health research



 “The science has never been better. By almost any measure, the opportunities we
 have today for getting to understand the major mental illnesses are unprecedented.”


Viewing the state of mental health in the United States        in the 1980s, at the NIMH. Later, as a professor of
from his vantage point as director of the National Institute   psychiatry at Emory University, he founded a National
of Mental Health (NIMH), Thomas R. Insel, M.D.,                Science Foundation-funded Center for Behavioral
perceives an uneven landscape. The good news, he says,         Neuroscience and led an NIH Center for Autism Re-
is that “the science has never been better. By almost any      search. He also directed the Yerkes Regional Primate
measure, the opportunities we have today for getting to        Research Center from 1994 to 1999. Dr. Insel was
understand the major mental illnesses – from autism to         awarded a NARSAD Distinguished Investigator Grant,
Alzheimer’s disease to eating disorders to the psychotic       in 2001, to explore whether variations in two genes play
illnesses and mood and anxiety disorders – are unpre-          a role in social behavior in schizophrenia and autism.
cedented. We’re gaining a foothold on many levels,             He was elected to the Brain & Behavior Research
from the molecular to the behavioral, or as we say at          Foundation (then NARSAD) Scientific Council in
the NIMH, ‘from the genome to the culturome.’”                 1999, a volunteer position he left when he was ap-
                                                               pointed to his present post in 2002.
He does not, however, see comparable progress concern-
ing the prevalence and treatment of mental illnesses.          “When I rejoined the NIMH after 20 years away from
Under his leadership, the NIMH recently initiated a            clinical care most of the changes I saw were not for the
comprehensive program aimed at leveling the field, a           better,” he says. “Treatments for the most part had not
strategic plan to narrow the gap between what’s discov-        improved, nor had outcomes when measured by such
ered in the lab and what gets applied in the clinic.           indices as employment, suicides and homelessness.
                                                               Access to care had actually declined. While the research
Gap between great science and better treatments                has certainly taken off, the areas where there has been
Dr. Insel’s appraisal draws upon a broad perspective. He       the most progress, genetics and neuroimaging, haven’t
began his career as a practicing psychiatrist. He turned       yet had any real impact on care. The country has an
to laboratory work doing basic research to study the           annual rate of 35,000 suicides. In the military, we’re
neurobiology of social behaviors during an earlier stint,      losing more soldiers to suicide than to combat.”



16 The Quarterly
                                                                         New Hope in Mental Health




  “We know now that no single gene is going to explain vulnerability to schizophrenia…
  That’s not a reason to give up – the same was true for cancer as recently as
  10 or 15 years ago. Rather, it’s a reason to accelerate our efforts.”




One treatment area where Dr. Insel does see an advance is      that are too frequently fatal. So understanding the sever-
the use of the medication clozapine to treat schizophrenia.    ity of these illnesses is where one needs to start. And
Clozapine was tested in the late 1980s on patients with        severity here is measured in morbidity and mortality.”
schizophrenia resistant to other treatments by Dr. Her-
bert Meltzer, a member of the Brain & Behavior Re-             Strategic plan to get to better results: The four Ps
search Foundation Scientific Council, and others at            At this writing the U.S. government is in a heated budget
Vanderbilt University. At present, however, clozapine is       debate that could mean cuts to research funding at the
used by fewer than one percent of people in the United         national level. In this climate Dr. Insel remains focused
States with schizophrenia, mainly because of concerns          on effectiveness. “The challenge now is to make sure
about a rare but potentially fatal side effect. Dr. Insel      the funds we do have are used for the greatest impact,”
points to schizophrenia as an example of how genetic           Dr. Insel says. This is where the NIMH strategic plan –
research can be applied to looking for biomarkers as has       what he and his colleagues call “the four Ps” – comes in.
been done in other areas of medicine.This would iden-
tify those at risk, a quest currently underway.                The first P is for pathophysiology. As Dr. Insel explains:
                                                               “We don’t really understand the pathophysiology of any
The disparity between research and care in mental health       of the mental illnesses in the way we now understand
can be explained, Dr. Insel says, by the sheer complexity      many medical problems. It’s imperative we make a large
of brain disorders.“We know now that no single gene is         investment toward learning the causes and mechanisms
going to explain vulnerability to schizophrenia nor one        of these disorders.”
neuroimaging result make possible a diagnosis or iden-
tify which patients should receive which treatment,” he        The second P is preemption. Brain disorders result from
said. “We may have had that hope a decade ago, but that        missteps in brain development, which raises the possibil-
was before we learned how complicated these disorders          ity of intervening at an earlier stage of illness. In schiz-
are. That’s not a reason to give up – the same was true        ophrenia, for example, psychosis, the point at which
for cancer as recently as 10 or 15 years ago. Rather, it’s     most people are first diagnosed, is a relatively late stage.
a reason to accelerate our efforts.”                           “It’s like the way we used to diagnose coronary artery
                                                               disease only after a myocardial infarction,” Dr. Insel says.
Mental health care: ‘separate and unequal’                     “We want to be able to identify biomarkers early in the
Stressing the importance of integrating mental health          cycle so that we can come up with more effective ways
into the larger health care picture, Dr. Insel observes that   to preempt disability.”
mental health continues to be ‘separate and unequal,’
with mental illnesses still considered qualitatively differ-   The third P is for personalized medicine. Syndromes such as
ent from other illnesses.                                      schizophrenia, autism and depression represent extreme-
                                                               ly heterogeneous disorders. As a result, treatments that
 “These are uncertain times economically, and difficult        work for one person often don’t work for another. “Un-
times in the provision of health care both for mental health   derstanding how to tailor treatments to the needs of
and for other medical problems. It’s important for peo-        each individual is a major priority. This requires a dif-
ple to realize the public health challenges in front of us,    ferent kind of clinical trial where the focus is on being
to recognize that these are very serious brain disorders       able to identify not just differences between treated and



                                                                                     www.bbrfoundation.org             17
New Hope in Mental Health



                                                                 out a way to do many things together. I think we have
                                                                 done this quite well in autism, where there is a coordi-
                                                                 nating body that brings together nonprofits along with
                                                                 the different federal agencies to create a strategic plan
                                                                 for research, to figure out where the gaps are and to
                                                                 close those gaps by working together.

                                                                 “We’ve done that in some very concrete ways, from
                                                                 specific studies that had to do with genetics and look-
                                                                 ing for biomarkers through sibling studies to now cre-
                                                                 ating a database that has more than 50,000 individuals
                                                                 in it that will be the kind of repository for both the
                                                                 publicly funded and privately funded research. So that’s
                                                                 a partnership that has grown up over the last 4 or 5
                                                                 years. I think it’s really making a difference for people
                                                                 with autism and their families.”

                                                                 Although such partnerships become even more critical
                                                                 when funding is tight, the pharmaceutical industry has
                                                                 largely retreated from the development of psychiatric
                                                                 medication, which Dr. Insel warns “should be of great
                                                                 concern to anybody who cares about mental illness
untreated individuals, but exactly who is responding to          since treatments generally are developed by industry.”
which treatment and why,” Dr. Insel says.
                                                                 In another kind of partnering, Dr. Insel acknowledges
The fourth P stands for public health impact, or, as Dr. Insel   “the vital role nonprofits play in supporting early stage
puts it,“getting to the endgame – having the measures that       investigations,” what he calls “venture science.” The
will reduce disability, unemployment, homelessness, sui-         Brain & Behavior Research Foundation is the nation’s
cide. It’s being able to ensure that people can truly recover    largest private funder of mental health research. Of the
and have the opportunity to participate fully in society.”       organization’s mission he says: “What is most difficult
                                                                 for scientists starting out, sometimes even for established
Joining forces to accelerate progress                            investigators exploring a new area of interest, is getting
Partnerships that bring together different sectors of the        that first small grant that allows them to collect the pilot
health care community for research and treatment devel-          data they need to be able to apply to NIH for funding.
opment might be called the “fifth P.” Dr. Insel points
to the example of a current plan for autism research that        “That certainly was true for me and I know the support
includes a database of 50,000 individuals to serve as a          from Brain & Behavior Research Foundation has been
repository for both publicly and privately funded studies.       critical to countless psychiatric researchers.”
In another instance, the Alzheimer’s Disease Neuroimag-
ing Initiative (ADNI), funded in part by the National            In his NIMH Director’s Blog for March 29, Dr. Insel
Institutes of Health (NIH), partnered with pharmaceu-            stated: “We are living through an extraordinary period
tical companies to study Alzheimer’s risk.                       of discovery in neuroscience, analogous to the exuberant
                                                                 periods of theoretical physics a century ago or micro-
“Partnerships become even more critical when funding             biology a half-century ago.” He reiterated this message
is tight. There’s an old expression that says if you want        for the readers of this article, asserting: “These are sci-
to go fast, go alone. If you want to go far, go together.        entifically the best of times, and that’s an enormously
We want to go both fast and far, so we have to figure            hopeful sign for the future.” O




18 The Quarterly
                                                                           New Hope in Mental Health




The Power of a Welcoming,
Empowering Workplace
Randy Lewis at Walgreen Co. leads
the way for other companies to employ
people with disabilities, brain and
behavior disorders




                                                                 and as a trainer of this innovative and highly successful
  “Corporations only live on paper. It’s                         program to other corporations, even arch rivals in the
  the people in the corporations.”                               marketplace. His division leads “boot camps” where
                                                                 managers of other corporations can come spend a week
While scientists work toward a future in which mental            or two to learn the ropes of how it all works. “AT&T
illness is better understood and better treated, another         has gone through boot camp,” he says.“Pepsico brought
hope long harbored by people with mental illnesses is            in a group of their international operators. A Brazilian
being fulfilled – real jobs with real paychecks in safe and      company came and is starting a program in Sao Paulo, and
welcoming workplaces. J. Randolph (Randy) Lewis,                 I’ve spoken a couple of times to businesses in Germany.”
Senior VP of Supply Chain and Logistics, Walgreen
Co., spoke to The Quarterly about a thoughtfully de-             What these executives see when they visit one of the
signed and highly successful program that he spearheaded         Walgreen sites where the program is in operation are
to provide employment opportunities for disabled work-           state-of-the-art, highly effective and cost-efficient distri-
ers, including people with mental illnesses. When asked          bution centers.What they may not initially see or realize
if he saw this as a responsibility for corporations – to offer   is that there are disabled and able employees working
employment opportunities for all people – he responded           side by side, often doing the same jobs, earning equal pay.
that, “Corporations only live on paper. It’s the people in       At the company’s distribution center in Anderson, S.C.,
the corporations. Most people want to do the right               the first site built specifically with the program in mind,
thing, most people want to help.”                                40 percent of the 600 workers are disabled, and, Mr.
                                                                 Lewis says, “It’s the most cost-effective building in our
Randy Lewis may be right. His program was launched in            chain and in the history of the company.”
2004 by Walgreen Co., and beyond the success within the
company, it has become a model for other organizations           Interestingly, the fact that the center is the most cost-ef-
and is being implemented by a number of major cor-               fective building is not his primary source of pride. He says
porations, including Lowe’s, Best Buy, Sears, Clarks and         the impact on the non-disabled employees is the most
GlaxoSmithKline. “And the list keeps growing,” he says.          important benefit of the program. “It brings out the
                                                                 better person in each of us,” Mr. Lewis says. And fortu-
Today he finds himself with a dual career, in his “day job”      nately for him, that has translated into high productivity.
leading logistics and distribution centers at Walgreen Co.



                                                                                        www.bbrfoundation.org             19
A second such center has since been built in Hartford,         in the door.” What made it possible for him to convince
Conn., where 50 percent of the workers are disabled,           Walgreen Co. to greenlight his idea was a 10-year track
and recently two of the company’s existing buildings           record at the company in a job in which 10,000 people
were retrofitted for the program. These efforts, while         working in 20 centers report to him.
costly, have rewarded the company, Mr. Lewis says,“with
an integrated workforce that has exceeded all our ex-          “When we started the program for the disabled, we had
pectations.” Beyond these new centers, Walgreen Co.            three objectives,” Mr. Lewis said. “First, to keep firmly
has extended its hiring of people with disabilities, em-       in mind that we’re a business and not a charity, we had
ploying more than 850 people (10 percent) across all           to be able to justify it to our shareholders and our other
20 distribution centers nationwide. The plan is to dou-        employees. Second, we had to have a sustainable model
ble those numbers in the coming years – and to roll out        we could show to other businesses and say this works
the program to Walgreen Co. retail stores.The first pilot      here, and it will work in your place. That was in our plan-
is underway, with the intention to fill 1 in 10 entry-         ning from the start.” Finally, he and his team decided
level positions with disabled workers by 2012.                 not to try to answer every question in advance.

Strong leadership translates a personal vision                 “That third objective was a key point because otherwise
into corporate success                                         we’d probably never have gotten it off the ground,” he
Randy Lewis’s motivation for starting the program was          says. “From my experience with my son, I had learned
personal. He has a son with autism, and like every par-        that so many of the things I worried about when he was
ent with a child with a disability, he worried for his son’s   diagnosed at age 3 – would he be able to tie his shoes,
future. “Where is he going to be? Is he going to be en-        would he get toilet trained, would I have to wrestle him
gaged in the world, or is he going to be sitting alone all     to the floor to get his hair cut – never came up. So we
day staring at a TV or computer screen?” Mr. Lewis was         set out with the idea that we’re going to go down this
certain that in his own company there were any num-            road without having all the questions answered upfront.
ber of jobs that his son and other disabled people could       And, he adds, with the knowledge that if we fail, it’ll be
perform, “but,” he says, “first they had to be able to get     the failure we’ll always be most proud of.”



20 The Quarterly
                                                                          New Hope in Mental Health




  “People don’t disclose and the
  mentally ill are still marginalized.
  It’s like the final group that still
  needs to overcome discrimination.”


By acknowledging not every question was answered, the
team was prepared to adapt quickly to handle challenges.
Some of the challenges, Mr. Lewis explains, required
modifying company policy; no easy feat in a corpora-
tion the size of Walgreen Co. For example, applicants
for employment in the distribution centers are supposed
to be able to do every job in the center, whether or not
this ever really proves to be necessary. This would clearly
not be possible for some disabled workers. Ultimately, the
company was willing to question its traditions in hiring
and adapt the policies that could change without neg-
atively impacting productivity. And they added training         together, they talk about how they were able to help a
for the managerial staff to learn how to effectively guide      disabled worker. They’ll boast about the creativity they
and supervise people who might never have held a job            used in making that person successful at a task.
before and might have low frustration levels.
                                                                Mr. Lewis is becoming increasingly confident that his
  “It’s about enabling full, productive                         second objective for the program – its sustainability that
  lives for these people.”                                      it will live beyond him – will be achieved. “I think that
                                                                now we have enough experience behind us so that this
                                                                can become part of our corporate DNA. If the program
Mental illness is a public health issue                         is to have a meaningful impact, it’s got to outlive me and
In speaking about mental illness in particular, Mr. Lewis       continue to broaden. This is not about me. Anybody
calls it a public health issue. “People don’t disclose and      can do it if they overcome their fear. Fear of the un-
the mentally ill are still marginalized. It’s like the final    known, fear of taking a risk, fear of working with people
group that still needs to overcome discrimination.” And         with disabilities. That’s why we throw open our doors
so his part in that process is to bring the disability out in   to other companies and tell them,‘We’ll help and advise
the open, to let employees work side by side as people          you if you’ll just take the chance.’ We also tell them,
and to recognize each other as such.“It’s about enabling        ‘This may not be the easiest thing you’ll ever do, but
full, productive lives for these people – and letting oth-      it’ll be the most meaningful.’”
ers help them get there.”
                                                                In 2009, in recognition of the remarkable contribution
“We’ve learned that sometimes a job is a lot more than          the program he started has made in the lives of hundreds,
a job,” Mr. Lewis says. “Some of these folks never knew         and potentially many thousands, of people with disabil-
what a weekend was. For them every day was like every           ities and their loved ones, the Brain & Behavior Research
other day. Now they have weekends, they have income,            Foundation (then NARSAD) awarded Randy Lewis its
they’re like everyone else.” And when the managers get          first Productive Lives Award. O



                                                                                      www.bbrfoundation.org           21
New Hope in Mental Health




                                              ‘Caught Between Optimism
                                              and Concern’
                                               Dr. Carol Tamminga, Brain & Behavior
                                               Research Foundation Scientific Council
                                               Member, speaks about the potential
                                               of mental health research today



The term “translational research” refers to the translation of    A major thrust of translational research in neuroscience
research findings into medical treatments based upon under-      now, she says, is toward “conceptual advances,” approaches
standing the underlying mechanisms of an illness. It is a        that go beyond simply trying to modify or improve ex-
key goal for neuroscientists confronting mental illnesses        isting modes of treatment.
for which available treatments remain inadequate or non-
existent. In light of these aspirations and in the context       Most existing treatments for mental illnesses, including
of the nation’s current funding uncertainties, neurosci-         antipsychotic and antidepressant drugs, target neuro-
entist Carol A. Tamminga, M.D., a member of the                  transmitters, such as dopamine and serotonin that relay
Brain & Behavior Research Foundation Scientific Coun-            information between nerve cells across the synapses in
cil, finds herself caught between optimism and concern.          the brain.

“I believe we’re really on the brink of being able to take       “These days our focus is moving to what happens after
the fabulous discoveries of neuroscience and apply them          neurotransmission, to postsynaptic cell signaling and the
to the treatment of diseases,” she says.“Our basic knowl-        relationship of those signaling systems to the functions
edge of the brain and how it works is growing by leaps           of neuronal populations and, in turn, to the alterations
and bounds, and opportunities for advancing our under-           in those functions that occur in psychiatric illness,” Dr.
standing of mental illness have never been better. But I         Tamminga says. “As we learn more about neuronal popu-
worry about a precipitous loss of federal funding. I fear        lation effects, we’ll be able to close in on which particu-
that psychiatry is one of the fields most vulnerable to          lar effects are associated with which symptoms, and how
cutbacks.” She also worries about an either-or mentality         we can modify those effects to relieve the symptoms.”
regarding the allotment of resources for research and
treatment development versus care of the mentally ill.           She compares the progression she is projecting for psy-
“The two should be paired, not opposed, and we simply            chiatry to the way recent advances in cardiology devel-
have to find a way to be able to do both.”                       oped, in which, on the way to ultimate answers, improved
                                                                 understanding has led to new treatments that have dra-
Conceptual advances move research forward                        matically improved survival rates. “For example if you
Dr.Tamminga is chief of translational research in schizo-        have congestive heart failure, what you want to do is
phrenia and head of the department of psychiatry at the          stimulate the heart muscle,” she says. “There may be
University of Texas Southwestern Medical Center at               hundreds of reasons why one gets heart failure, but once
Dallas, where she holds the Communities Foundation               it happens, the question is how to modify activity back
of Texas Chair in Brain Science.                                 toward normal function.That doesn’t mean we take our



22 The Quarterly
                                                                          New Hope in Mental Health
                                                                 momentum in basic science research now that will con-
  Creative, novel approaches are what                            tinue because it’s so interesting, really on the verge of
  Dr. Tamminga looks for each year as                            getting very good and very exciting.” In her view the
  she helps to screen the hundreds of                            combination of sufficient funding and a new genera-
  applications for NARSAD Grants,                                tion of researchers “asking the right questions” are what
                                                                 will bring us to a new place in scientific discovery. O
  which she’s been doing since 1994.

eyes off trying to understand the causes of illness, or how        Dr. Tamminga on
to prevent illness, but in the meantime, with regard to            Brain & Behavior Research
psychiatry, if we can define the alterations in the activity
in the brain, we can influence that activity to treat the
                                                                   Foundation Research Priorities
behaviors associated with illness.”
                                                                   Basic Research: “Before we can understand
                                                                   anything about the disease state we have to under-
One of the novel approaches Dr.Tamminga points to as
                                                                   stand the normal state: I see the most important
promising centers on the possibility of exploiting neuro-
                                                                   changes coming from the bottom up, coming from
plasticity, which is the brain’s ability to change in response
                                                                   our understanding of the science of the brain and
to environmental stimuli and form new neuronal connec-
                                                                   then our increasing ability to apply the science to
tions. “We haven’t yet learned enough to harness this
                                                                   brain diseases.”
plasticity to change symptoms of mental illness,” she says,
“but I believe that it will probably require an approach           New Technologies: “Human brain research is
combining medication with brain exercises, or what we              generating many new approaches to see how treat-
might call cognitive remediation.”                                 ments are influencing a patient’s brain, including
                                                                   human imaging and electrophysiological mapping
Funding creative research is key                                   approaches.These techniques provide online and
Creative, novel approaches are what Dr.Tamminga looks              dynamic feedback about disease and treatment
for each year as she helps to screen the hundreds of appli-        effects; we will also be able to apply these approaches
cations for NARSAD Grants, which she’s been doing                  to diagnosis in order to discriminate diagnoses
since 1994. “We’ve never wanted to fund the same old               from each other based on biological knowledge.”
thing, or projects for which other funding is readily
available. We like areas that may be risky, but if they            New Diagnostic Tools/Early Intervention
succeed might bring real change as has often happened              Techniques: “Early intervention is an approach
with research initiated with NARSAD Grant support.”                with considerable promise, if we only knew how
She, herself, is a current recipient of a Distinguished In-        to identify the proper individuals with mental ill-
vestigator award with which her lab is exploring what              ness who ought to receive the early treatments.The
she says is a “highly speculative model of psychosis.”             field needs to work on developing concrete bio-
                                                                   logical markers of functional brain diseases in
Throughout her years of association, and particularly at           order to provide proper prophylactic treatment.
the present moment of uncertain funding, Dr.Tamminga               Until then, we should be conservative about guess-
has been a strong advocate for Brain & Behavior Research           ing who will need the treatments.”
Foundation. Beyond its critical grant awarding role, she
is inspired, she says, by the families coping with mental          Next Generation Treatments: “The idea now,
illness who give it their time, energy and money, “begin-          for example in schizophrenia, is that there are fam-
ning, of course, with Steve and Connie Lieber and their            ilies of symptoms – psychosis, cognitive problems, de-
ceaseless efforts in support of scientific discovery.              pression – and to be able to treat each of these with
                                                                   their own optimal medication.We have treatments
“The Brain & Behavior Research Foundation funds                    for psychosis, but we don’t have any medications for
people who are creative, people who bring in new                   cognitive dysfunction. So, all of us are looking for
methodologies and points of view,” Dr. Tamminga says.              targets, different molecular targets for treatments
And while concerned about the precarious state of fed-             to improve things like attention and memory.”O
eral funding, she remains optimistic. “There’s so much



                                                                                       www.bbrfoundation.org                 23
New Hope in Mental Health




                                                 Joining Forces for Hope

                                                 Constance E. Lieber, president emerita
                                                 and long time donor, Brain & Behavior
                                                 Research Foundation, continues to push
                                                 for a better life for her daughter and the
                                                 millions of others living with mental illness


                                                                   Mrs. Lieber’s evaluation is cause for serious concern. It
  “There was a time when psychiatry                                is based on a 30-plus-year intimate acquaintance with the
  was a beggar at the science table.”                              mental health field. Mrs. Lieber’s knowledge stems from
                                                                   her own personal struggle as a mother, her work with
                                                                   countless other struggling families, and from her immer-
For more than a quarter of a century, Constance and                sion into the psychiatric community and the science of
Stephen Lieber have provided unwavering moral and                  mental illness as she led the development of NARSAD.
material support on the quest to unravel the mysteries             Of the immeasurable emotional, physical and financial
of the brain to better understand and treat mental illness.        burdens of caring for a family member with mental
Through their association with the Brain & Behavior                illness, she says, “It’s a full time job. It takes a toll on
Research Foundation, formerly NARSAD, and through                  everyone in the family, and the psychological fallout can
their endowment of academic research centers, profes-              be devastating.”
sorships, research scholarships and awards, Connie and
Steve, as they are known throughout the mental health              Frustration finds outlet with founding of NARSAD
community, have contributed significantly to revolu-               The Liebers’ personal confrontation with mental illness
tionary advances in the field.                                     began in the 1970s when their daughter, Janice, was
                                                                   diagnosed with schizophrenia.Their ensuing frustration
“There was a time when psychiatry was a beggar at the sci-         with the limited treatments available, exacerbated by the
ence table, but now,” as Mrs. Lieber enthusiastically notes,       stigma associated with mental illness, less prevalent today
“brain research is at the forefront of the scientific endeavor.”   but far from eradicated, led them to want to learn all
                                                                   they could about the field. What they learned instilled
In contrast, her view of current efforts to provide help to        in them the overwhelming conviction that what was
people with mental illnesses is less rosy. She sees the            needed above all was more scientific discovery into
national mental health scene as hobbled by “inadequate             these illnesses: discoveries to understand what causes the
recognition of the staggering problems incurred by mental          illnesses to occur, to identify new treatment options and
illness.” And, she says,“The real and present potential for        to light the path toward prevention and cures. The oppor-
rehabilitation and recovery is too often impeded by in-            tunity to put this conviction into action came just a few
sufficient services for patients and families, insufficient        years later, in the early 1980s, via a fortuitous meeting
dissemination of information and insufficient funding              with Columbia University psychiatrist Herbert Pardes,
for research.”                                                     M.D., at a conference on schizophrenia.“Herb mentioned
                                                                   that a new organization was being formed to foster


24 The Quarterly
                                                                            New Hope in Mental Health

research on brain and behavior disorders,” Mrs. Lieber           Dr. Alice Medalia, director of psychiatric rehabilitation
recalls, “and I said to Steve, ‘that’s for us.’”                 at Columbia University Medical Center, to help people
                                                                 with mental illnesses improve their cognitive skills and
The couple became the principal early backers of the             social interaction. It’s “a wonderful program for those
fledgling National Alliance for Research on Schizophre-          who can afford it,” Ms. Lieber says. “That’s the rub.”
nia and Depression (NARSAD).They became members
of the board of directors, of which Mr. Lieber is currently      Her long involvement with mental health issues has fos-
chairman. Dr. Pardes, now president and CEO of New               tered in Connie Lieber a passionate conviction of the need
York-Presbyterian Hospital, was the founding president of        for providing more hope and help to people with mental
the organization’s Scientific Council, a post he still holds.    illness, and not just for people with the means to pay for
It was during the course of Mrs. Lieber’s tenure as second       services. She has strong opinions about the measures that
president of Brain & Behavior Research Foundation                need to be taken, and that can and should be taken. Still
(then NARSAD), from 1989 to 2007, that the organiza-             at the top of her list is “research, research and more research.
tion grew to become the world’s largest private funder           But,” she insists, “we have to fund recovery as well. A lot
of brain and behavior research, awarding hundreds of             of people don’t believe in recovery, but people can re-
grants annually to scientists throughout the world.              cover. We desperately need more remediation services.”

The recent change of name to the Brain & Behavior Re-            Recovery is possible where science, society
search Foundation more accurately reflects the broadened         and service converge
range of the conditions under study by the scientists it         One way affordable services should be made available, she
supports.Through her years with the organization, Mrs.           says, is through community-supported mental health cen-
Lieber has seen firsthand the fears and frustrations faced       ters. She also points to donor-supported facilities such as
by patients, family members and mental health profes-            Fountain House in New York City. At Fountain House,
sionals, many of whom seek information and counsel at            people recovering from mental illness volunteer their
the foundation’s public education events.                        time to help run the organization, which provides con-
                                                                 nections to education opportunities, housing, jobs and
Progress comes at a cost                                         other rehabilitative services for the mentally ill.
Mrs. Lieber concedes that, overall, the picture has improved
since the time her daughter first fell ill, at least for those   She stresses the need for “more services up and down the
families like hers, who have access to up-to-date informa-       line, because so many are suffering and don’t know where
tion and live within range of good medical and social            to turn. There need to be resources in every commu-
services.The first real break for the Liebers came in the        nity where people can go to find a full range of treat-
late 1980s, when they learned about a new medication,            ments – medical, psychological, behavioral, cognitive.
called clozapine, still in clinical trial, which was meant       There has to be a reevaluation of clinical practice with an
specifically for schizophrenia patients like Janice who were     emphasis on rehabilitation. People have to inform them-
unable to cope with the side effects of the existing anti-       selves and take action to urge Congress to support the
psychotics. As it happened, clozapine was being tested           National Institute of Mental Health and to advocate for
with the most severely affected patients with schizophre-        more funding for both research and support services.
nia by Herbert Meltzer, M.D., a member of the Brain &
Behavior Research Foundation Scientific Council. Based           “The scientific progress has been impressive,” Mrs. Lieber
on his advice, Janice was put on clozapine. It was the first     says.“We are now in a period where more accurate, earlier
antipsychotic she was able to tolerate, more than 10 years       diagnoses can be achieved and more and better treat-
after her initial diagnosis, and her condition stabilized.       ments developed, but,” she adds, “opening pathways to
                                                                 recovery cannot be achieved simply through the indi-
The psychotic symptoms of schizophrenia – the voices             vidual efforts of patients and caregivers. It requires the
and hallucinations – are the first perceived and most            combined efforts of a large scientific community and a
dramatic manifestations of the illness, but it is the cogni-     society dedicated to overcoming these disorders. The
tive problems – deficits that develop with such processes        evidence that combined societal and scientific effort can
as attention and memory – that can cause the most dele-          produce results is beginning to emerge. Patients and
terious and long-lasting effects. Janice is currently en-        their families can now begin to see the possibility of a
rolled at the Learning Center, a program developed by            normal life.” O


                                                                                         www.bbrfoundation.org               25
New Hope in Mental Health


                                         A Different Kind of Therapy
                                         for Rehabilitation

                                         Kenn Dudek talks about Fountain House
                                         in New York City and how it supports
                                         recovery in mental illness through its
                                         participative community model

                                     There is no ques-
                                     tion whether men-        “Once you get medications you need
                                     tal health services      to do something else with your life.
                                     and rehabilitation       People need to pay as much attention
and recovery programs in the nonprofit sector have un-
dergone major changes and advancements, says Kenn
                                                              to the environmental side as the
Dudek, president of Fountain House in New York City.          biological side of the illness.”
The 63-year-old organization he leads has seen many
changes, though its core values remain. “The therapy of      mental illness, and that need is met by psychiatrists and
Fountain House is a working community,” Mr. Dudek            therapists. “Once you get medications you need to do
says. His big question is how to get the appropriate         something else with your life. People need to pay as much
recognition of the importance of this type of “therapy”      attention to the environmental side as the biological side
in recovery so that progress can reach the next level.       of the illness.” And so, at Fountain House, the focus is on
                                                             the environmental side of the illness.
Fountain House is a working community in the heart of
NewYork City that bustles with activity on any given day.    Mr. Dudek has worked in the field of mental health
Members, who are locals living with mental illness, share    since 1975. His first job was as an aid in a nursing home
responsibility with staff to keep things running, from       in Massachusetts. Patients included many young people
greeting visitors to reviewing new applications for mem-     who had been discharged from the state mental hospital.
bership to growing lettuce in their hydroponic grow          In 1985 Mr. Dudek was part of a group of professionals
room. Fountain House operates seven main activity            who visited Fountain House and studied its Clubhouse
areas – culinary, clerical, education, employment, hor-      Model as part of a national training program funded by
ticulture, research, and reception and membership.           a grant from the National Institute of Mental Health
Through this activity and participative model, Fountain      (NIMH). Herb Pardes, M.D., president of the Brain &
House has come to be a community of its own for many         Behavior Research Foundation Scientific Council, was
mentally ill in New York City. It offers a supportive        head of NIMH at the time and a supporter of the train-
physical space, creates opportunities for productive con-    ing program, Mr. Dudek said. In the years following his
tribution and enables the establishment of social ties and   training, as director of Community Support for the
consistent relationships.                                    State of Massachusetts, Mr. Dudek started 25 programs
                                                             like Fountain House that are still in operation today. He
What Fountain House does not offer is medication or          became the director of Fountain House in 1992 and
therapy services onsite. Members have access to referrals    later its executive director and is president today.
with partner organizations for those needs. Kenn Dudek,
Fountain House president, explains this policy. He be-       Global Clubhouse Rehabilitation Model
lieves that medication and conventional therapy are only     The national training program that guided Mr. Dudek
one step in the recovery process for those living with       in replicating the Clubhouse Model has evolved into the


26 The Quarterly
                                                                          New Hope in Mental Health
International Center for Clubhouse Development (ICCD),          ple with mental illness in the state and federal govern-
founded in 1994. Collaborating with other Clubhouses,           ment,” he says. Fountain House is 63 years old, a world
standards were developed to guide how a Clubhouse               leader and model for recovery in the field, and yet there
would function, and templates for management and or-            is not a good funding stream in place to support it. “It’s
ganization were created, Mr. Dudek explained. Today,            completely ridiculous,” he says with frustration.
consultants work with individual clubhouses to offi-
cially certify each location. Certification teams are always    From his view at a nonprofit mental health organization,
composed of a member and a staff worker, drawn from             Mr. Dudek said that states have abandoned their role in
a pool of specially trained clubhouse colleagues from           major mental health. States need to reclaim control of
all over the world.                                             mental health funding and fund the programs that are
                                                                needed and most helpful, he said.
There are currently 150 certified Clubhouses around the
world in 30 countries, including Argentina, Germany,            The role of research in recovery
China and South Africa. The biennial international              Fountain House began in 1948, and its community-based
Clubhouse Seminar is planned for this summer in                 approach predates the first generation of antipsychotic
Stockholm, Sweden.                                              medications. Mr. Dudek is optimistic about the effects
                                                                of medications in helping people with mental illness and
Replication of the Clubhouse model at Fountain House            realistic about the challenge of people staying on their
is also broadened through ongoing Colleague Training            medications. Many medications force people to make
first originated with the NIMH grant. Trainings run             trade-offs, Mr. Dudek said. He pointed to side effects
for three weeks and participants are immersed in the            such as weight gain and loss of sex drive that often dis-
full community experience at Fountain House and stay            courage people from staying on their medication.
in the Fountain House guest house, Mr. Dudek said.
Since 1977, more than 2,000 people have come to                 “I have hope for the advancement of medications, but I
Fountain House to learn how to establish a Clubhouse.           believe you will always need environmental interventions
                                                                as well as medical intervention,” Mr. Dudek said. He’s seen
Treating the social isolation                                   awakenings in people over his long career, but thinks it
Mr. Dudek stresses that the biggest problem with men-           takes a combination of medications and environmental
tal illness is the effect of social isolation on individuals.   support for true recovery to be realized.
In the past, and even still today, people with mental ill-
ness are hospitalized, homeless or living at home with          While scientific research has made advances in treating and
their parents, which limits interaction with peers.             understanding mental illness, Mr. Dudek would like to
“You’re alone and have lost connections to friends,” he         see more research into the effects of places like Fountain
said. “Family is the last group you have connections            House and the working community model. “There is
with. Places like Fountain House connect you with               just as much to learn about the environmental side as the
others. Programs can help with job training, but that           biological side, and it has a lot to teach people.”
doesn’t change the fact that many people with mental
illness are completely isolated. You can’t just do job          One possibility, he suggests, would be to examine brain
training, education and housing for people with men-            scans of members when they first arrive at Fountain
tal illness.You need to help create a community.”               House and brain scans of members after they have been
                                                                a member for a year or two. His hope is that such re-
And Fountain House does just that. Members are the              search will reveal what he’s experienced on a day-to-
receptionists, teachers, tour guides, chefs and more that       day basis in his time at Fountain House: There is value
keep the place going. Fountain House is purposefully            in a working community approach and what the com-
understaffed in order to solicit the contributions of its       munity does for social isolation and social networking
members. “The illness is only part of your life,” Mr.           is helping people recover.
Dudek said. “Recovery is about separating the person
from the illness.”                                              “Recovery means you have the illness, but you have a life,”
                                                                Mr. Dudek said.“I think we’re missing a piece of the puz-
And Mr. Dudek worries that this type of critical sup-           zle by ignoring places like Fountain House. The brain
port isn’t recognized as essential. “There is still a major     is complex. Outside the brain is complex, too.” We need
misunderstanding about what it takes to support peo-            to treat the whole person to really get to recovery. O


                                                                                      www.bbrfoundation.org             27
New Treatments/Therapies




New Treatments/
Therapies
As research breakthroughs continue to be made,
new treatments and therapies for people living
with mental illness point toward recovery



                      THREE STEPS
                      TO
                      MENTAL HEALTH
                      Step 1:
                      DISCOVERY
                      Understanding malfunctions
                      in the brain

                      Step 2:
                      TREATMENT
                      Reducing symptoms
                      and retraining the brain

                      Step 3:
                      RECOVERY
                      Supporting rehabilitation
                      to enable full, productive lives



28 The Quarterly
                                                                            New Treatments/Therapies




Smart Phone App Helps Veterans Manage PTSD
Veterans dealing with symptoms of Post-traumatic Stress Disorder (PTSD) can turn to their smart phones for help
anytime with the PTSD Coach application created by the Department of Veterans Affairs (VA) and the Department of
Defense. “This is about giving Veterans and Service members the help they earned when and where they need it,” said
Secretary of Veterans Affairs Eric K. Shinseki. PTSD Coach lets users track their PTSD symptoms, links them with
local sources of support, provides accurate information about PTSD, and teaches helpful individualized strategies for
managing PTSD symptoms at any moment. The free PTSD Coach app is now available for download from the iTunes
store and will be available for Android devices by the end of the spring. The PTSD Coach is primarily designed to
enhance services for individuals who are already receiving mental health care, though it is certainly helpful for those
considering entering care and those who just want to learn more about PTSD.
Source: U.S. Department of Veterans Affairs Press Release



Combination of Medication and Tai Chi Beats Back Depression in the Elderly, Study Shows
When they combined a weekly tai chi exercise class with a standard depression treatment for a group of depressed
elderly adults, researchers at UCLA found greater improvement in the level of depression – along with improved
quality of life, better memory and cognition, and more overall energy. In the study, 112 adults age 60 or older with
major depression were treated with the drug escitalopram for approximately four weeks. From among those participants,
73 who showed only partial improvement continued on medication but were also randomly assigned to 10 weeks of
either a tai chi class for two hours per week or a health education class for two hours per week. Researchers found
that among the tai chi participants, 94 percent achieved a score of less than 10 on the Hamilton Rating Scale for
Depression (a cut-off score of 10/11 is generally regarded as appropriate for the diagnosis of depression), with 65
percent achieving remission (a score of 6 or less). By comparison, among participants who received health education,
77 percent achieved scores of 10 or less, with 51 percent achieving remission.
Source: Science Daily/American Journal of Geriatric Psychiatry



Could Lou Gehrig’s ALS Medication Riluzole Treat Bipolar Depression?
While insufficient serotonin may be one cause of depression, researchers are exploring another possible cause – dys-
regulation of glutamate. Glutamate is the most abundant excitatory neurotransmitter in the body. Riluzole (Rilutek),
a prescription drug commonly used to treat Lou Gehrig’s disease or amyotrophic lateral sclerosis (ALS), reduces the
release of glutamate while increasing its uptake. Some studies have shown that Riluzole is effective in treating acute
bipolar depression alone or in combination with other antidepressants. Perhaps even more important in respect to treat-
ing bipolar depression, Riluzole and other medications that target glutamate may have a lower risk of triggering a switch
to mania. Riluzole is not being used in routine clinical practice yet – but look for more research and potentially new
treatment options that target glutamate in the near future.
Source: Candida Fink, M.D./Psych Central




                                                                                      www.bbrfoundation.org          29
Momentum


Momentum
Events Calendar
For more details on research and fundraising events,
visit our website: bbrfoundation.org/events
TEAM UP! FUNDRAISING EVENTS
RESEARCH EVENTS

MAY                                                          May 26 in Montreal, Quebec
May 1 in Collegeville, Pa.                                   Frontiers in Mental Health
Art Festival to Benefit Schizophrenia                        Brain & Behavior Research Foundation co-sponsored with
Research in Honor of Jerry Zoll                              Graham Boeckh Foundation and the Gairdner Foundation;
Ursinus College, 10 a.m. - 4 p.m.                            featuring Brain & Behavior Research Foundation Grantees.
                                                             www.gairdner.org/calendar
May 13 in Paoli, Pa.
Benefit Concert for Mental Health                            JUNE
www.benefit4mentalhealth.org                                 June 20 in Harrison Township, Mich.
                                                             19th Annual Michigan NARSAD Golf Classic
May 14 in Chino, Calif.                                      For information contact Elizabeth Puleo-Tague (313) 882-1482
The Chino Valley Walk for Mental Health
in Memory of Jason Tennies                                   June 22 in Cold Spring, N.Y.
www.jasontennies.org                                         Brain & Behavior Research Foundation,
                                                             St. Johnland Nursing Center and Cold Spring
May 15 in Ridgewood, N.J.                                    Harbor Laboratory Research Event
Fourth Annual Taking Strides                                 Presentations by Brain & Behavior Research Foundation Sci-
Against Mental Illness Walk                                  entific Council members on New Treatments for Depression
www.againstmentalillness.org                                 and Bipolar with Q&A. Details: 7 p.m. at Cold Spring Harbor
                                                             Laboratory, 1 Bungtown Road, Cold Spring Harbor, N.Y.
May 19 in Dallas, Texas
New Hope in Mental Health Research Series                    JULY
featuring Carol A.Tamminga, M.D., Brain & Behavior
                                                             July 22 in Manorville, N.Y.
Research Foundation Scientific Council Member, Professor
                                                             5th Annual Chrissy’s Wish Memorial Golf Outing
and Chair, Department of Psychiatry, University of Texas
Southwestern Medical Center at Dallas                        Rock Hill Golf & Country Club
                                                             Chrissy’s Wish was established in memory of Christina Rossi.
Brain & Behavior Research Foundation brings together
                                                             As a result of several fundraising events, Chrissy’s Wish has
leading scientists in a unique nationwide event. Event is
                                                             raised more than $170,000 for Brain & Behavior Research
open to the public at no charge. Registration is required:
                                                             Foundation. www.chrissyswish.com
bbrfoundation.org/events/nhmhseries

May 23                                                       July 23 in Pleasant Grove, Utah
Noon - 1 p.m. Eastern Time                                   Silver Linings For Loved Ones Family Hike
Meet the Scientist: A Virtual Q&A Discussion                 in Memory of Brian Taylor
                                                             Join us on a family-friendly hike and promote mental health
featuring Daniel R.Weinberger, M.D., Brain & Behavior
                                                             research. Proceeds will benefit Brain & Behavior Research
Research Foundation Scientific Council Member,
                                                             Foundation. silverliningsforlovedones.blogspot.com
National Institute of Mental Health
Register online at bbrfoundation.org/events/webinar



30 The Quarterly
                                                                                       Momentum

       New Hope in Mental Health Research Series
              Breakthroughs and Discoveries
Brain & Behavior Research Foundation brings together leading scientists in a unique nationwide
event. Join us for small, intimate meetings with leading scientists discussing research advances and
hope for the future of mental health research.

                           We are coming to your state!
California, Illinois, New York, Louisiana, Massachusetts, Washington, Florida, Pennsylvania, Missouri,
Colorado, Ohio, Minnesota, New Jersey, Connecticut

Go to www.bbrfoundation.org/events/nhmhseries.org for event details

                        Complimentary admission – invite family and friends!


                National A
                          wards
                                 Dinner

                              Join us as we cele
                                                 brate our
                             Outstanding Ach
                                               ievement in
                         Scientific Researc
                                           h Award Winn                      ers
                                                   &
                         Productive Lives
                                                    Award Winners
                             Wednesda
                                     y, October
                                                26, 2011
                                    The Pierre
                                  New York
                                            City

                     Awards Din
                                  ner Tickets
                      or e-mail e             : 1-800-829
                                 vents@bbr               -8289
                                             foundation
                                                          .org


                                                                          www.bbrfoundation.org        31
     Momentum


    HEALTHY MINDS ACROSS AMERICA
    Discovery to Recovery through Science


   M
                      ore than 40 institutions across the United States and Canada partnered with NARSAD, now
                      Brain & Behavior Research Foundation, in presenting its “Healthy Minds Across America” series of
                      public talks in 2010. Each event helped to bring science to families seeking hope for better
                      treatments of a broad range of mental illnesses. The following pages contain highlights of
                      presentations from various venues in the series. Full transcripts of the talks are available at
                      www.bbrfoundatin.org/events. Click “Past Research Events.”


In partnership with                         From Mind to Molecule:
University of Pennsylvania
                                            The Powerful New Tools of Research
                                            Raquel Gur, M.D., Ph.D.

                                            All medical research strives to untangle complex processes in the body so as to be
                                            able to intervene better in treating illness. Biological psychiatrists are working
                                            to be able to question what in the brain makes individuals vulnerable for mental
                                            illness and to categorize illnesses.Toward that end, they are drawing upon research
                                            tools never before available; tools for imaging the brain’s structure and activity,
                                            for studying genes and genomes, cells and molecules; tools that are powerful,
                                            safe and reliable. Neuroscience has entered an era in which questions that were
                                            once unanswerable can now be answered.

                                            The oldest method of study in medicine is clinical observation: how a patient
                                            looks, acts and feels – what is called a phenotype. As opposed to the genotype,
Raquel Gur, M.D., Ph.D.                     which is the basic set of genes common to a species, the phenotype is the way
1999 Distinguished Investigator             genes play out in a particular individual: brown eyes or blue, for instance. But also
2009 Lieber Prize for Outstanding           evident are such things as signs of psychosis.There is also a method called evoked
Achievement in Schizophrenia Research       phenotype. Physicians look for underlying heart problems by using a stress test.
University of Pennsylvania School           Behavioral problems can be evoked, for example, with memory tests or by how
of Medicine                                 well or poorly a patient reads social cues, or with brain imaging that observes
                                            activity or blood flow in the brain when a patient performs a specific task.

                                            An important, ubiquitous research tool is the use of animal models.While there
 Neuroscience has                           can be no exact animal models of human mental illnesses – a mouse with schiz-
 entered an era in                          ophrenia, for instance – specific features associated with a disorder, such as prob-
                                            lems of learning and memory seen in schizophrenia, can be induced in animals
 which questions                            through an array of genetic technologies.
 that were once
 unanswerable can                           Endophenotype, also called intermediate phenotype, relates to behaviors and
                                            brain activity seen in people with an illness that are also present in first-degree
 now be answered.                           relatives who may or may not be ill. Many current studies are examining families
                                            of people with schizophrenia and other mental illnesses to gain clues as to the
                                            reasons illness develops in one member of the family and not another.


     32 The Quarterly
                                                                                                     Momentum


These methods are likened to zooming in and out with a camera; zooming in
for as close a picture as possible, zooming out to try to see what is common to
different disorders based on the growing evidence of overlap across disorders in
phenotype, symptoms and the brain systems underlying particular behaviors.


Personalizing Medicine: Toward Individual Genetic                                          In partnership with
Profiles as Predictors of Drug Effectiveness                                               University of California, Irvine
Steven G. Potkin, M.D.

In the future – and to some limited extent today – knowledge of a person’s
genetic background will help to determine their medical treatment. Genes will
predict whether a drug will work for that individual, or cause a serious side effect,
without the costly and sometimes dangerous process of trial and error. Already,
genetic information combined with new types of brain imaging is giving neuro-
scientists unprecedented access to the brain’s structure and functioning, allow-
ing them to define areas important to understanding normal brain function and
mental illness. This new knowledge will help them develop better drugs faster.

Researchers are applying gene studies and imaging to a variety of projects in-
volving gene discovery and drug testing. One study they conducted identified
schizophrenia patients who had a heightened genetic risk for developing tardive
dyskinesia, a condition of involuntary facial tics that can be a troubling side ef-        Steven G. Potkin, M.D.
fect of some antipsychotic drugs. Researchers were further able, with imaging              Scientific Council Member
technology, to pinpoint the regions of the brain that tardive dyskinesia affected.         University of California, Irvine

A new technology called genome-wide association study (GWAS) now makes it
possible to view entire genomes at one time. Iloperidone (Fanapt) is a new anti-
psychotic drug recently approved by the Food and Drug Administration. Before
approval, researchers performed a genome-wide scan of 250,000 single-nucleo-
tide polymorphisms, or SNPS, (pronounced “snips”). These are tiny variations
in a gene’s composition from one individual to another. They found six varia-                  In the future – and
tions – out of the 250,000 scanned – that predicted positive response to the drug.             to some limited
A drug may be effective, but cause serious side effects. Some of these effects may             extent today –
be rare, but nonetheless the drug may be taken off the market unless prediction                knowledge of a
can be made as to who will be affected. Another study has focused on the debate                person’s genetic
surrounding whether antidepressants cause suicidal thinking. In the study, adult
patients with depression were given the antidepressant citalopram (Celexa). Some               background will
of the patients did develop suicidal thoughts. All of those had two particular                 help to determine
gene variations. Based on this finding, risk of suicidality can now be predicted,              their medical
at least in these instances, in advance.
                                                                                               treatment.
Among many other explorations, researchers recently identified two schizo-
phrenia-related genes and their activity in the brain, as well as a gene for elevated
Alzheimer’s disease risk.The lab has also been testing the effectiveness of a drug
for Alzheimer’s based on patient genotypes, their individual gene profiles.

Go to www.bbrfoundation.org/events and click on ‘Past Events’
to read the full transcripts of presentations made at
Healthy Minds Across America venues
                                                                                        www.bbrfoundation.org            33
Glossary


Glossary
 Helpful definitions of terms used in this issue.

SNPS (page 2): SNPs, or single-nucleotide polymorphisms (pronounced “snips”), are single-letter variations in the
3-billion-letter genetic code that differ between individuals. They are the most frequent type of variation in the
genome.

Optogenetics (page 3): Optogenetics is an experimental method involving the use of light to make neurons fire one at
a time, opening new vistas to understand the mechanisms behind depression and other brain and behavior disorders.
Optogenetics was invented by Karl Deisseroth, M.D., Ph.D., Stanford University, with the support of a NARSAD
Young Investigator Grant.

Copy-Number Variations (CNVs) (page 4): CNVs are extra or missing segments of DNA in a person’s genome. Many
CNVs result in a person having multiple copies of genes that fall within the “duplicated” region; or no copies at all,
if the region in question is “deleted” rather than copied. The average person has several dozen CNVs. Only rarely
do these extra or missing segments of DNA include genes that play roles in diseases such as schizophrenia or autism.

Human Genome Project (page 6): The Human Genome Project was a 13-year effort to determine the sequences of
the 3 billion chemical units, or “base-pairs,” that make up the full length of the human genome, and to identify all
the approximately 21,000 genes in human DNA. Researchers, including many Brain & Behavior Research Founda-
tion grantees, study data from the Human Genome Project in an effort to uncover the genetic causes of brain and
behavior disorders.

Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) (page 8): DREADDs are manmade recep-
tor molecules that can be genetically introduced into any cell (so far, just in laboratory mice) that enable scientists to
switch “on” and “off ” selected nerve cells in the brain. They provide a means of determining precisely which effects
of a drug to attribute to the drug’s action on its intended target(s), and which (if any) are generated by so-called “off-
target effects,” i.e., impacts on parts of the cell or neural circuitry that are not expected. This technology was invented
by Bryan Roth, M.D., Ph.D., University of North Carolina Chapel Hill Medical School, with the support of a
NARSAD Distinguished Investigator Grant. Using DREADDS, Dr. Roth’s team of researchers recently reported
success in teasing out the details of neural circuitry that had long eluded scientists’ best efforts – one that connects
several brain regions involved in the biology of addiction.

Pathophysiology (page 17): Pathophysiology is the study of the biological and physical symptoms of disease as they
connect with the underlying abnormalities and physiological disturbances.

Translational research (page 22): Translational research refers to the translation of basic scientific research findings into
new medical treatments and diagnostics based upon understanding the underlying mechanisms of an illness.

Phenotype (page 32): The unique way in which an individual’s genetic sequence is “expressed,” for instance, in the
form of traits such as eye color or height or presence or absence of heritable illnesses.

Genotype (page 32): All of the information contained within an individual’s genetic sequence, whether “expressed” or
“silent.” No two human beings have precisely the same genotype, since every person has unique genomic variations.
(The presence of SNPs and CNVs – see definitions above – guarantee that this is the case.)



34 The Quarterly
  How I turned a $60,000 NARSAD Grant
into more than $8.5 million worth of additional
                depression research funding
                                    Helen S. Mayberg, M.D., NARSAD Grant recipient in 1991, 1995 and 2002




Helen Mayberg's success as a researcher can be attributed, in part, to her first NARSAD Grant, which
enabled her to demonstrate the feasibility and practical application of Deep Brain Stimulation on
treatment-resistant patients with depression. Dr. Mayberg, one of the world's leading authorities on
neurology and depression, went on to receive numerous NIMH and institutional grants thanks to
Brain & Behavior Research Foundation funding her work with a seed grant.

Dr. Mayberg's story is a familiar one to us at Brain & Behavior Research Foundation as many Foundation-
funded scientists have received additional grant support equaling, on average, 19 times their original
NARSAD Grants. 100% of all donations go directly to our researchers thanks to the generosity of two
family foundations that underwrite operating costs.

No other mental health research organization can say this.


To learn more about how you can invest in the most
promising brain and behavior research like that of Dr.
Mayberg's, please call us at (516) 829-0091 or visit our
website at www.bbrfoundation.org.
Meet a Young Investigator


Meet a Young Investigator
                                                Karuna Subramaniam, Ph.D.
                                                University of California San Francisco
                                                2010 NARSAD Young Investigator Grant


                            What made you pursue schizophrenia research as a career?
                            Schizophrenia research first sparked my interest when one of my oldest friends developed schizophrenia.
                            She was plagued by hallucinations where she’d hear voices telling her “You are bad!” She also frequently
                            exhibited disorganized symptoms where she’d suddenly burst out laughing without any reason. I was
                            especially struck at how treatment-resistant she was to medications.With the aim of developing novel
                            treatments, I decided to pursue schizophrenia research because: 1) pharmacological treatment has shown
                            limited effects, and 2) recent studies have revealed that the neural impairments in schizophrenia are not
                            immutably fixed.The time is ripe for developing interventions that target improved neural and cognitive
                            functioning in patients.

What role does your NARSAD Young Investigator Grant play
in your research?
The NARSAD Grant enables me to launch my career as an independent
investigator in the study of how inducing a positive mood can enhance cognitive
processes that are impaired in schizophrenia patients.

What do you hope to discover through the research funded
by your Young Investigator Grant?
My NARSAD Grant is funding the study of mood-cognition interactions in
schizophrenia.This work is an extension of my doctoral thesis, which revealed the
cognitive-enhancing effects of a positive mood during problem solving in healthy
subjects (See article in New York Times: http://nyti.ms/fGhCwW). If we’re
able to show similar cognitive-enhancing effects in schizophrenia patients, this re-
search would suggest that behavioral interventions that increase hedonic capacity
could be very useful in developing novel treatments for schizophrenia.

                                      How is brain and behavior research affecting the lives of those living with
                                      mental illness – and/or for future generations?
                                      Recent research has shown evidence of improvement in community functioning by combining
                                      psychosocial treatments with cognitive remediation in schizophrenia patients (Eack et al.,
                                      2009; McGurk and Wykes, 2008). In our recent study, we’ve shown that after schizophrenia
                                      patients completed 80 hours of neuroscience-informed computerized cognitive training, they
                                      demonstrated enhanced neural activity within the medial prefrontal cortex, which correlates
                                      with better cognition and predicts long-term improvement in social functioning (Subramaniam
                                      et al. (under review), Neuron).

                                        Where do you think the next big breakthrough will come in mental
                                        illness research?
                                        The evidence now indicates that most brain and behavior disorders are triggered by the interac-
tion of genetic factors with adverse environmental events. I think the next breakthrough is likely to arise from integrating genetic and
functional imaging studies; ideally, researchers would discover ways to inactivate the expression of critical genes which would other-
wise predispose the brain toward a pattern of neurochemical and functional abnormalities associated with psychosis.


36 The Quarterly
Support Our Campaign
                       for Productive Lives
Our Campaign Objective:
                  Accelerate the breakthroughs with $200 million
                  in new support over five years

What will $200 million achieve?
   •    $120 million additional funding for Young Investigators
        o Increase grant amount from $60,000 to $90,000 over two years
        o Grants awarded to the most promising young scientists
   •    $50 million additional funding for Independent Investigators
        o Grants awarded to researchers during critical period between initiation of research
           and receipt of sustained funding
   •    $30 million additional funding for Distinguished Investigators
        o Grants used to fund a particularly talented, established investigator



All the ways you can give:
   • Make a Gift Now                  • Research Partner Program                     • Annual Gift
   • Planned Giving                   • Family Foundations                           • Foundation Giving
   • Team Up!

For more information visit bbrfoundation.org

       Address: 60 Cutter Mill Road, Suite 404, Great Neck NY 11021   Phone: (516) 829.0091   Website: bbrfoundation.org




                                                                           Why We Support The Foundation

                                                                         We have been supporters of NARSAD and now
                                                                       Brain & Behavior Research Foundation since 1995.
                                                                       Having a son suffering from schizophrenia has been
                                                                         a difficult journey for our family, but seeing the
                                                                       remarkable research by the Foundation investigators
                                                                      has provided the hope to keep on fighting. There is no
                                                                         other organization on the planet better poised to
                                                                         make real breakthroughs in brain and behavioor
                                                                                science – and bring the joy of living
                                                                                    back to our dear son, Daniel.
                                                                                      –Miton and Tamar Maltz
                                60 Cutter Mill Road, Suite 404
                                Great Neck, NY 11021




          Investing in Breakthroughs — To Find a Cure

OUR MISSION:
The Brain & Behavior Research Foundation is committed to alleviating the suffering of mental illness by
awarding grants that will lead to advances and breakthroughs in scientific research.


HOW WE DO IT:
100% of all donor contributions for research are invested in NARSAD Grants leading to discoveries in
understanding causes and improving treatments of disorders in children and adults, such as depression, bipolar
disorder, schizophrenia, autism, attention-deficit hyperactivity disorder, and anxiety disorders like obsessive-
compulsive and post-traumatic stress disorders.


OUR CREDENTIALS:
For a quarter of a century, we have awarded nearly $300 million worldwide to more than 3,300 scientists
carefully selected by our prestigious Scientific Council.




To find out more about Brain & Behavior Research Foundation, the research it supports and how
you can become involved, please call us at 800.829.8289 or visit www.bbrfoundation.org.



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