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 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 said, cautioning, however, that the results also
could point to environmental factors, such as loss of a
parent at an early age or physical or sexual abuse.
In this study, Potash and his team looked at 638 men
and women diagnosed with early-onset major depression and
at 2,176 of their first-degree family members. The subjects
were drawn from the Genetics of Recurrent Early-onset
Depression project — known as GenRED — a
multicenter study of patients enrolled between 1999 and
2003 by researchers at Johns Hopkins and elsewhere.
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 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 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," Potash said. "Our large study allows us the
numbers to examine these questions in subgroups."
Potash credits lead author Francis Mondimore, of the
Johns Hopkins Psychiatry
Department, 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
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, a method that documents the onset and
duration of mood episodes and the presence or absence of
such symptoms as loss of interest in or ability to enjoy
life, feeling guilty or down, fatigue, lack of
concentration, loss of appetite or weight and thoughts of
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 Johns Hopkins School of
Major depression and chronicity were diagnosed using
the Diagnostic and Statistical Manual of Mental Disorders
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 Johns
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., director of
the Department of Psychiatry, is the Johns Hopkins
Funding for the study was provided by the National
Institute of Mental Health. Other researchers from Johns
Hopkins who contributed to this study are DePaulo; Dean F.
MacKinnon, also of the School of Medicine; and Peter P.
Zandi, of the Bloomberg School of Public Health.