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SHERVERT H. FRAZIER RESEARCH INSTITUTE

The Shervert H. Frazier Research Institute Staff

The Shervert H. Frazier Research Institute
(click to enlarge)

Frazier Institute Collaborations

Frazier Institute Collaborations
(click to enlarge)

The Shervert H. Frazier Research Institute at McLean Hospital supports a multidisciplinary team of basic and clinical scientists devoted to understanding the causes and developing new treatments for major psychiatric disorders, especially mood, psychotic, anxiety, and neurodegenerative disorders. Techniques and discoveries arise from clinical, laboratory and brain imaging components.

Principal Researchers

Director
Bruce M. Cohen, M.D., Ph.D.

Research Coordinator
Suzann M. Babb, MS

Executive Administrator
Fontini Savvides

Clinical Collaborators:
Brian Brennan, M.D.
Laura Flynn, B.A.
Brent Forester, M.D.
Jean Frazier, M.D.
Peter Harris, M.D., Ph.D.
Michael Henry, M.D.
Jennifer Kahn, B.A.
Jeanne Lothrop, B.S.
Beth Murphy, M.D., Ph.D.
Sarah Young, B.A.

Imaging Collaborators:
Xiaoying Fan, M.D.
Marc Kaufman, Ph.D.
Döst Öngur, M.D., Ph.D.
Elizabeth Quattrocki Knight, M.D., Ph.D.
Michael Rohan, Ph.D.

Table I: Clinical Trials
Pharmacology
Kappa agents
Adrenergic agents
Glutamatergic agents
Nutriceutical/Biological Agents
Omega 3 fatty acids plus cytidine
Oral SAMe for bipolar depression
Mitochondrial supplements
Intranasal insulin
Low field magnetic stimulation
Real-Time Functional MR Biofeedback
Download Mania Acute Changes Scale (MACS)
Adobe portable document format (pdf)
Table II: Major Preclinical Projects
Pharmacology:
Kappa agents
Insulin signaling pathway
Trace amine modulators
Stress reducing agents
Neurorepair
Glial and neuronal deficit models of illness  
Neurogenerative agents
Repair by stem cells or viruses
Mitochondrial repair/replacement
Search for gene targets with Broad Institute

Human, iPS cells, and in animal models

Preclinical Collaborators:
Cécile Béguin, Ph.D.
Anita Bechtholt-Gompf, Ph.D.

Sabina Berretta, M.D.
Edgar (Ned) Buttner, M.D., Ph.D.
William Carlezon, Ph.D.
Elena Chartoff, Ph.D.
Sarah Elmiligy, B.S.
Rakesh Karmacharya, M.D., Ph.D.
Yenarae Lee, B.A.
Noah McKenna, B.A.
Donna McPhie, Ph.D.
Edward Meloni, Ph.D.
Thomas Munro, Ph.D.
Angelica Ortiz
David Potter, M.A.
Laura Sargent, B.S.
Jordan W. Smoller, M.D., Sc.D.
Kai Sonntag, M.D., Ph.D.
Jonathan Wong, M.S.
Nancy Ye, M.S.

Biostatisticians:
Nicholas Lange, Ph.D.

Clinical Trials

An overview of our Clinical Trials effort is presented in Table I. Trials of kappa modulators have moved from the laboratory to the clinical arena for the first time. Ongoing or follow-up trials of promising early studies include the pursuit of low field magnetic stimulation (LFMS, which originally came from observations in our Brain Imaging Center), the combination of omega-3 fatty acids and cytidine (which may have synergistic effects on mood as suggested in our preclinical studies) and the glutamatergic agents riluzole and memantine (which showed success in early clinical trials). We have begun several pilot studies that could represent significant new directions for therapeutics, including the treatment of bipolar disorder with mitochondrial supplements and bipolar depression with SAMe, and have begun a collaboration testing intranasal insulin as a treatment for chronic psychosis (schizophrenia). We have initiated studies to evaluate whether rtfMRI neurofeedback can be used in the treatment of mood and anxiety disorders.

Mania Acute Changes Scale (MACS)

In the past, rating scales for mania have been designed to assess symptoms over many hours or days. Clinical researchers supported by the Frazier Institute are interested in looking at more rapid changes in manic symptoms. To do this, they have developed a novel rating scale called the Mania Acute Rating Scale, or the MACS for short. The MACS is being used at McLean in clinical trials of new agents for treating mania and bipolar disorder.

Genetics

With the sequencing of the human genome and the increasing power of genetic analysis, the pace of discovery of risk genes for human illness, including psychiatric disorders, has accelerated. We are collaborating with the Broad Institute at MIT and Harvard and its affiliated hospitals to identify genes that determine

At present, over 250 patients are volunteering for these studies yearly.

Preclinical Research

Studies performed in our preclinical component are summarized in Table II. Animal studies at our center on the effects of current antidepressant and antimanic drugs point to an important role for the peptide neurotransmitter dynorphin, acting through kappa receptors, in the determination of mood state and psychosis. Based on this information, we are working to synthesize and test agents that act at kappa receptors to produce mood stabilizing effects. We are studying whether agents that modulate trace amines may help regulate mood and cognition. We have promising leads on new ways to treat neuropsychiatric disorders, including depression, bipolar disorder, schizophrenia and Alzheimer’s disease, through nerve and glial cell growth in the brain and through remodeling or replacement of dysfunctional cell elements. We have new evidence on the circuits underlying the stress response, which may trigger episodes of PTSD and other psychiatric disorders. We have initiated a new model system using C. elegans to study current drugs and have evidence on new targets for novel treatments of bipolar disorder and schizophrenia.

Brain Imaging

Brain imaging remains an important component of our work. It is focused on techniques and projects directly relevant to treatment development and testing. The work specifically emphasizes spectroscopic imaging of brain chemistry and functional imaging of brain activity related to psychiatric illness and treatment response. Imaging studies have not only suggested the value of LFMS, but helped suggest the use of uridine derivatives, glutamatergic agents and mitochondrial supplements to correct abnormal metabolic findings in bipolar disorder and schizophrenia.

Some Recent Publications of Investigators in the Frazier Institute

Recently Published Articles:

Recently Published Abstracts:

This work is supported by federal grants, foundation awards and private gifts

08.2013