Contacts:
Sarah Goodwin

Kathi Ovnic
Holly Korschun
October 4, 1999


EMBARGOED FOR RELEASE until 2 p.m., E.D.T., Wed., Oct. 6, 1999

 

NEUROCHEMICAL LINK BETWEEN CHILDHOOD TRAUMA AND ADULT DEPRESSION IS FOCUS OF $13 MILLION NIH CENTER GRANT TO EMORY

A large team of neuroscientists at the Emory University School of Medicine has been awarded a five-year, $13 million grant from the National Institute of Mental Health of the National Institutes of Health to support establishment of the Emory Conte Center for the Neuroscience of Mental Disorders.

Investigators working at the center will be led by Charles B. Nemeroff, M.D., Ph.D., Reunette W. Harris Professor and Chairman of Psychiatry and Behavioral Sciences at Emory. Four researchers from Yale University and one from Princeton University are included along with the Emory co-investigators.

The hypothesis upon which all center research will be based is the Stress-Diathesis Model of Mood Disorders, put forth by Dr. Nemeroff in the June 1998 issue of Scientific American. The theory holds that depression experienced in adulthood is associated in many patients with aberrant brain chemistry altered in childhood by adverse early life stress. The theory is based on rodent, primate and human research conducted largely by the Emory team.

"We postulate a model in which genetic vulnerability coupled with early trauma in a critical plastic period of development results in sensitization of neural systems which, when exposed to even mild stressors in adulthood, respond in a heightened manner, resulting in the neurobiological alterations that underlie the syndrome of depression," Dr. Nemeroff says. "These studies have important implications not only for the neurobiology of depression, but the development of novel treatment strategies for depression, certain anxiety disorders and child abuse."

The investigators believe early abuse or neglect activates the "fight-or-flight" stress response and persistently increases activity in the brain cells most responsive to stress ­ those containing corticotropin-releasing factor (CRF).

Indeed, in separate experiments, Paul M. Plotsky, Ph.D., SmithKline Beecham Professor of Psychiatry and Behavioral Sciences, and Dr. Nemeroff showed in different rodent models that rat pups exposed to early life stressors develop the same heightened CRF activity in adulthood as that measured in human adults with clinical depression. Preliminary findings from these investigators suggest that the altered brain chemistry of affected adult rats can be normalized with certain antidepressants. Treating exposed rats with paroxetine (Paxil, a selective serotonin reuptake inhibitor) or with a soon-to-be-released novel antidepressant, reboxetine (a selective norepinephrine reuptake inhibitor), returns CRF neuronal activity to normal, and normalizes corticosterone production in that system responsible for hormonally regulating the body's response to stress: the hypothalamic-pituitary-adrenal (HPA) axis.

Dr. Nemeroff and colleagues at Yerkes Regional Primate Research Center of Emory are studying young rhesus monkeys, after a pilot study conducted with collaborators at the State University of New York at Brooklyn and Columbia University revealed that early stress (from a variable foraging routine) results in similar CRF neuronal abnormalities in adulthood. Furthermore, in a preliminary study of women with depression who were sexually or physically abused as children, the Emory team again noted similar stress hormone abnormalities.

The researchers will have the opportunity to continue their groundbreaking animal work in the first six project areas of the new center grant. Projects 1-3 focus on the role of specific neurotransmitter systems implicated in the Stress-Diathesis Model. Signal transduction processes will be investigated in Project 4 and the more fundamental developmental processes of neurogenesis and remodeling of the hippocampus will be addressed in Project 5. The acoustic startle reflex will be evaluated in Project 6.

The later two project areas will allow the researchers to better apply animal findings to human disease. The HPA axis function of adult women abused as children will be evaluated in Project 7, and an assessment of whether maternal pre- or postpartum depression can be considered an early life stressor of infants is the focus of Project 8.

Project areas are designated by the following:

 

Project 1: CORTICOTROPIN-RELEASING FACTOR (CRF)
in the Neurobiology of Stress, Anxiety and Depression-like Syndrome
Paul M. Plotsky, Ph.D., project principal investigator
 
Project 2: SEROTONIN
in the Neurobiology of Stress, Anxiety and Depression-like Syndrome
Michael J. Owens, Ph.D., project principal investigator
 
Project 3:DOPAMINE AND NOREPINEPHRINE
in the Neurobiology of Stress, Anxiety and Depression-like Syndrome
Michael J. Kuhar, Ph.D., (Yerkes), project principal investigator
 
Project 4: SIGNAL TRANSDUCTION SYSTEMS
in the Neurobiology of Stress, Anxiety and Depression-like Syndrome
Eric J. Nestler, M.D., Ph.D., (Yale), project principal investigator
 
Project 5:HIPPOCAMPAL NEUROGENESIS AND REMODELING
in the Neurobiology of Stress, Anxiety and Depression-like Syndrome
Elizabeth Gould, Ph.D., (Princeton), project principal investigator
 
Project 6:ACOUSTIC STARTLE REFLEX
in the Neurobiology of Stress, Anxiety and Depression-like Syndrome
Michael Davis, Ph.D. , project principal investigator
 
Project 7:CHILD ABUSE AND DEPRESSION IN WOMEN
Dr. Nemeroff, J. Douglas Bremner, M.D., (Yale) and Dennis S. Charney, (Yale), project principal investigators
 
Project 8:PRE- AND POSTPARTUM MATERNAL DEPRESSION:
Effect on Children
Sherryl Goodman, Ph.D., and Zachary N. Stowe, M.D., project principal investigators



"A major strength of the Emory center is our broad range of multidisciplinary basic and clinical neuroscience research, exemplified by the availability of both rodent and primate early life stress animal models of depression, as well as the patient populations available for study," Dr. Nemeroff says.

In addition, work at the center will be supported by administrative, assay, functional brain imaging and laboratory animal cores.

"The rat and monkey data raise profound clinical and public health questions," Dr. Nemeroff says in the Scientific American paper. "In the U.S. alone in 1995, more than three million children were reportedly abused or neglected, and at least a million of those reports were verified. If the effects in human beings resemble those of the animals, the findings imply that abuse or neglect may produce permanent changes in the developing brain ­ changes that chronically boost the output of, and responsiveness to, CRF, and therefore increase the victims' lifelong vulnerability to depression."

The Scientific American paper is available in its entirety on the Internet at: http://www.sciam.com/1998/0698issue/0698nemeroff.html.

 

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