People whose first-degree relatives developed chronic major depression while young are at very high risk for developing the disorder themselves, according to an article in the September issue of the American Journal of Psychiatry. The multicenter study, led by Johns Hopkins psychiatrist James B. Potash, MD, involved more than 600 patients and their families.

Siblings, parents or children of people diagnosed with chronic major depression before the age of 31 years had a 2.52-to-1 likelihood of also having the disorder. Moreover, first-degree relatives of patients diagnosed with chronic major depression before the age of 13 years had a 6.17-to-1 likelihood 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 said, although he cautioned 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, researchers looked at 638 men and women diagnosed with early-onset major depression and 2,176 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 at Hopkins and other research centers.

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 had this form of disease (37.8 percent), whereas the remaining 412 had a total of 148 relatives with chronic depression (20.2 percent). A breakdown of these results showed that 58 people diagnosed before the age of 13 years with chronic major depression had 44 family members who also had the disease (48.9 percent). The remaining 69 people diagnosed with major depression before age 13 had 17 relatives (15.9 percent) 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,” said Potash. “Our large study allows us the numbers to examine these questions in subgroups.”

Lead author Francis Mondimore, MD, of the Department of Psychiatry at Hopkins, had observed 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. 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 said 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), a 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) 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, 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.