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Severest Form Of Depression Ravages Families, University Of Pittsburgh Study Finds

PITTSBURGH, September 10, 2001 — While researchers have known for some time that depression tends to run in families, a landmark study from the University of Pittsburgh School of Medicine examined the genetic and environmental impact of recurrent, early-onset major depression on affected individuals and their family members. Among the results, researchers found that nearly half of close relatives of individuals who developed recurrent depression before the age of 25 also suffered from one or more mood disorders themselves.

The study, published in today’s American Journal of Medical Genetics, is one of the largest to characterize the mental and other health related problems of individuals with this subtype of clinical depression and their family members. Researchers evaluated more than 1,300 members of 81 families identified by a relative with recurrent, early-onset major depression (RE-MDD). They found that the rate of mood disorders among these family members far exceeded that of the general population. In fact, close relatives (parents, siblings, children) of the individuals with RE-MDD developed major depression at eight times the rate of the general population, while extended relatives had a rate four times higher than normal.

“The news is not good for families of individuals with RE-MDD,” said George S. Zubenko, M.D., Ph.D., professor of psychiatry at the University of Pittsburgh School of Medicine and adjunct professor of biological sciences at Carnegie-Mellon University. “This form of clinical depression runs strongly in families, is often associated with other mental disorders that include prominent disturbances of mood, and has a significant negative impact on the health and longevity of patients and their family members.”

Among the other mental disorders that commonly accompany major depression are alcohol and drug use disorders, anxiety disorders, and certain personality disorders. “Because RE-MDD and these other mental disorders occur at elevated rates in the same families, share clinical features, and often respond to the same treatments, we suspect that there may also be similarities in their root causes,” said Dr. Zubenko. “Current evidence suggests that these disorders arise in part from the effects of overlapping groups of susceptibility genes. Nongenetic influences also play a role. For example, having a close relative with a disabling psychiatric condition often leads to increased stress and caregiving burden that may precipitate clinical depression and other health problems among the remaining family members.”

Other alarming data from the study show an extraordinary effect of RE-MDD on the longevity of family members that the researchers say may begin before birth. The mean and median ages of death for relatives of people with RE-MDD were shifted toward younger ages across the entire lifespan, including a five-fold increase in the infant mortality rate. In the study, family members lived an average of eight fewer years; more than 40 percent died before reaching age 65. Older family members were also at greater than average risk for developing neurodegenerative diseases such as Alzheimer’s.

“From the time of conception until death, a dynamic balance involving the birth of neurons, their migration and formation of interconnections, and programmed cell death play a critical role in determining normal brain activity,” said Dr. Zubenko. “Inborn or prenatal errors that alter this process may contribute to the later development of psychiatric disorders as well as hastening or exacerbating the development of neurodegenerative events.”

Dr. Zubenko cautioned that further research needs to be done to clarify his findings.

“Our findings have clear and current significance for physicians and other health care providers,” according to Dr. Zubenko. “Clinical depression and related disorders constitute major public health problems that warrant early detection and appropriate treatment. These considerations are of special concern for patients who suffer from recurrent depressive episodes that first emerge early in life. Furthermore, a high index of suspicion for mood and related disorders appears warranted during evaluations of family members who may under-report signs or symptoms of these conditions during routine examinations or during evaluations of other maladies. Screening for alcohol and substance abuse, as well as suicide risk, in this high risk group also seems prudent,” he said. “In the foreseeable future, results from our ongoing genetic studies that rely on a unique library of transformed cell lines representing these families may also provide new opportunities for treating or even preventing these disorders.”

Other authors on the study are: Wendy N. Zubenko, Ed.D., R.N., C.S., and Duane G. Spiker, M.D., of the University of Pittsburgh School of Medicine; Donna E. Giles, Ph.D., of the University of Pittsburgh School of Medicine and University of Rochester School of Medicine; and Barry B. Kaplan, Ph.D., of the Intramural Research Program, National Institute of Mental Health.

This study was supported by the National Institute of Mental Health. Those interested in participating in similar research studies underway at the University of Pittsburgh School of Medicine may call toll-free 877-485-7568.  All calls are confidential.

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