Hopkins-led study finds that chronic form of depression runs in families

Findings validate search for possible genetic link

The odds are more than two to one that people whose close relatives developed chronic severe unipolar depression when they were young will have it, too, according to results of a multicenter analysis of more than 600 people and their families.

Results of the study, published in the September issue of the American Journal of Psychiatry, with Johns Hopkins psychiatrist James B. Potash, M.D., as senior author, show that siblings, parents or children of people diagnosed with chronic major depression before the age of 31 have a 2.52-to-1 chance of also having the disorder. Moreover, first-degree relatives of patients diagnosed with chronic major depression before the age of 13 have a 6.17-to-1 chance of having it. "This chronic form of major depression can be uniquely disabling because of its persistence. Our finding that this aspect of the illness runs in families suggests the value of searching for contributory genes," Potash says, although he cautions that the results also could point to environmental factors, such as loss of a parent at an early age or physical and sexual abuse.

In this study, Potash and his team looked at 638 men and women diagnosed with early-onset major depression and 2,176 of their first-degree family members. The subjects were drawn from the Genetics of Recurrent Early-onset Depression (GenRED) project, a multicenter study of patients enrolled between 1999 and 2003 by Hopkins and other researchers.

Analysis showed that the 226 people interviewed in GenRED who were diagnosed before the age of 31 with chronic major depression had 352 family members who also suffered from this form of disease (37.8%), whereas the remaining 412 had a total of 148 relatives with chronic depression (20.2%). A breakdown of these results showed that 58 people diagnosed before the age of 13 with chronic major depression had 44 family members who also had the disease (48.9%). The remaining 69 people diagnosed with major depression before age 13 had 17 relatives (15.9%) with chronic illness.

"We have known for a long time that major depression runs in families, but we are still working on determining whether certain subtypes of the illness do so more strongly than others," says Potash. Our large study allows us the numbers to examine these questions in subgroups."

Potash credits lead author Francis Mondimore, M.D., of the Department of Psychiatry at Hopkins, with observing that many of the study participants reported having been depressed "as long as [they] can remember." This led Mondimore to focus on chronic -- or persistent -- depression over time. An estimated 30 percent of those with major depressive disorder have symptoms most or all of the time, with only incomplete remissions, over many years, according to Potash.

Mondimore says a similar technique, examining a subtype of illness, was used to discover a familial relationship in breast cancer in women -- a finding that paved the way to discovering a link between the BRCA1 gene and that disease.

Data for the GenRED project and for first-degree relatives was gathered using the Diagnostic Interview for Genetic Studies (DIGS), an method that documents the onset and duration of mood episodes and the presence or absence of such symptoms as loss of interest or ability to enjoy life, feeling guilty or down, fatigue, lack of concentration, loss of appetite or weight, and thoughts of death.

Study subjects were recruited to GenRED by the University of Iowa College of Medicine, Rush University Medical College, Columbia University Medical Center, University of Pittsburgh Medical Center, University of Pennsylvania School of Medicine and The Johns Hopkins University School of Medicine.

Major depression and chronicity were diagnosed using the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) -- a standard guide for the classification of mental illness. DSM-IV criteria for major depression include the presence of five or more depressive symptoms that have lasted for two or more weeks and that significantly impair the person's life. In the current study, subjects had to have been diagnosed with major depression before the age of 31, have at least one sibling with major depression who was diagnosed before the age of 41, and have no history of schizophrenia or bipolar (manic-depressive) illness.

GenRED II, a larger study now under way at Hopkins and five other sites, is recruiting 2,700 people to identify genes for major depression. Data also is being collected on other potential contributing factors, such as early childhood trauma. J. Raymond DePaulo Jr., M.D., director of the Department of Psychiatry, is the Hopkins principal investigator.

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Funding for the study was provided by the National Institute of Mental Health. Other researchers from the Johns Hopkins University School of Medicine who contributed to this study are DePaulo, Dean F. MacKinnon, M.D., of the Department of Psychiatry; and Peter P. Zandi, Ph.D., M.P.H., M.H., of Hopkins' Bloomberg School of Public Health.

Additional researchers include Raymond P. Crowe, M.D., of the University of Iowa College of Medicine; William A. Scheftner, M.D., of Rush University Medical College; and Myrna M. Weissman, Ph.D., of Columbia University Medical Center.


Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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