PRESS RELEASES

Five McLean Hospital Scientists Receive NARSAD's Prestigious 2008 Young Investigator Award

Each Receives $60,000 Two-Year Grant for Research on Psychiatric Disorders

FOR IMMEDIATE RELEASE:
May 05, 2008

CONTACT:

NARSAD
Kristen Simone
516-829-0091
ksimone@narsad.org

Natalie Greaves
516-829-0091
ngreaves@narsad.org

Great Neck, N.Y - Five McLean Hospital scientists have been selected by NARSAD, the world's leading charity dedicated to mental health research, to each receive a 2008 Young Investigator Award.

NARSAD is the world's leading donor-supported organization dedicated to funding research on brain and psychiatric disorders. The McLean Hospital scientists - including investigators affiliated with Harvard University - are five of 220 early-career scientists in the United States and 11 other countries who will receive funds this year from NARSAD to advance their research on mental illnesses.

Each of the scientists will receive $60,000 from NARSAD over the next two years to study a variety of topics:

More detailed summaries of the NARSAD-funded work being pursued by each of these outstanding young scientists are appended to this release.

As exemplified by the research topics of the five McLean Hospital scientists, recipients of NARSAD's 2008 Young Investigator grants are involved in many novel research projects, ranging from the genetics of mental illness to the assessment of novel treatments to sophisticated epidemiological research.

Their work should bring new scientific insight to such conditions as depression, bipolar disorder, schizophrenia, anxiety, childhood mental disorders and other serious conditions affecting tens of millions of adults and children worldwide.

"The young scientists whom NARSAD selects for participation in our grant program represent the very best in their respective areas of expertise. They have been judged by our distinguished Scientific Council as having developed innovative and promising research programs," said Geoff Birkett, president of NARSAD. "Their work will accelerate progress in the study of all areas of psychiatric disorders, and is leading not only to better treatments but also, we are confident, cures."

"NARSAD's Young Investigator awards play a unique and invaluable role, particularly in a federal funding environment that is widely acknowledged to be difficult. The awards have a proud history of attracting the finest young talent to the field and expanding the research potential for mental health," added Herbert Pardes, M.D., president and CEO of NewYork-Presbyterian Hospital, who is also president of NARSAD's Scientific Council. Comprised of 103 prominent leaders in mental health research, the Council reviews the project proposals NARSAD receives and makes funding recommendations.

NARSAD created the Young Investigator Award to help the most promising scientists who are now entering research-i.e., post-doctoral fellows, advanced-standing medical residents, and assistant professors-to generate pilot data necessary for larger grants. NARSAD also annually offers a Distinguished Investigator Award, supporting innovative research by full professors or their equivalent with $100,000 one-year grants, and an Independent Investigator Award, providing two-year grants of $100,000 to mid-career scientists, such as associate professors or their equivalent.

NARSAD raises funds to advance research on the causes, treatment and prevention of psychiatric disorders. Since it began giving grants in 1987, as the National Alliance for Research on Schizophrenia and Depression, NARSAD has awarded $233 million through 3,470 research grants to scientists in 428 institutions in the U.S. and 27 other countries. For additional information on the work of NARSAD, the research it supports, and various psychiatric disorders, visit the organization's Web site at www.narsad.org.

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Abstracts:

Heather C. Brenhouse, Ph.D., of McLean Hospital/Harvard University, will use animal models to learn how fine-tuning of the cortex during adolescence is altered by early-life stress and to intervene in this window of vulnerability. Both schizophrenia and depression are postulated to be due to inflammation as well as genetic predisposition. The proposed research will investigate the use of COX-2 inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs) that have important neurochemical function, as a prophylactic treatment for cortical events that may trigger onset of illness.

Brian P. Brennan, M.D., of McLean Hospital/Harvard University, aims to explore the use of a pharmaceutical drug in the treatment of bipolar depression. Dr. Brennan proposes a 6-week placebo-controlled, double-blind, parallel group study investigating the use of ALCAR 1000mg and ALA 600mg or placebo taken twice daily as an augmentation treatment in 30 men and women with bipolar depression who have not responded to an adequate trial of lithium or valproate. He will measure change in brain lactate and glutamate using proton magnetic resonance spectroscopy (1H-MRS) enabling correlation of clinical response with improvement in mitochondrial functioning. Primary analysis will be the association between clinical response and change in brain lactate and glutamate levels. Because there are no reports of use of these medications in patients with bipolar disorder, this preliminary study is designed to test the principle of whether enhancing mitochondrial functioning may be a viable treatment in bipolar depression, and to correlate clinical findings with direct corroboration of chemical brain changes.

Brent Forester, M.D., of McLean Hospital/Harvard University , will explore the use of a compound, CoEnzyme Q10 (CoQ10), to treat bipolar disorder in older patients for whom current treatments are often only partially effective and incur significant side effects. While the underlying mechanisms of bipolar disorder remain unclear, some studies implicate abnormalities in energy metabolism, the function of cell constituents called mitochondria. CoQ10 has been shown to enhance mitochondrial function in patients with neurodegenerative disorders such as Parkinson's disease. The study will apply a novel adaptation of magnetic resonance spectroscopy to assess its effects on mood and energy markers in the bipolar patients.

Glenn T. Konopaske, M.D., of McLean Hospital/Harvard University , will conduct preliminary studies in animals that are required to work out the technical details and assess the potential confounding effects that antipsychotic treatment might have on glutamate homeostasis. Dr. Konopaske proposes two studies that will 1) use 13C nuclear magnetic resonance spectroscopy to assess glutamate homeostasis in the frontal cortex of rats that have been exposed to ketamine to simulate the effects of schizophrenia; and 2) determine the effect clozapine and haloperidol have on glutamate homeostasis in the frontal cortex of rats using 13C magnetic resonance spectroscopy. The results of these experiments will guide the design of future 13C magnetic resonance spectroscopy studies in schizophrenia subjects and aid greatly in their interpretation.

Morgane M. Thomsen, Ph.D., of McLean Hospital/Harvard University , is examining the role of the muscarinic cholinergic receptors (mAchR's) in the pathophysiology and treatment of schizophrenia. There are five known mAchR's (M1-M5). It is unknown which of these receptors may have potential to mediate antipsychotic effects, cognitive improvements, or undesirable effects in schizophrenic patients, thus far severely limiting the usefulness of drugs acting at mAchR's. The aim of the present project is to identify individual mAchR's as potential targets for new antipsychotic drugs, either alone or as adjuvant medication that may enhance the benefits of current treatments for schizophrenia. Specifically it will evaluate in rodents the antipsychotic potential of selective M1- and M4-agonist drugs by testing selective agonist and antagonist toxins in the prepulse inhibition (PPI) and locomotor activity assays, both alone and in combination with known antipsychotic medications (haloperidol, clozapine). This research could contribute to the development of a novel class of antipsychotic drugs.

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