A Johns Hopkins-led study has found evidence that a
genetic tendency toward suicide has been linked to a
particular area of the genome on chromosome 2 that has been
implicated in two additional recent studies of attempted
suicide.
"We're hoping our findings will eventually lead to
tests that can identify those at high risk for attempting
suicide," said lead author Virginia Willour, an assistant
professor in the
Department of Psychiatry at
the School of Medicine. An estimated 4.6 percent of
Americans ages 15 to 54 have tried to take their lives,
according to Willour.
The investigators conducted a family linkage study in
which they searched for commonalities in the genomes of
family members with bipolar disorder and a history of
attempted suicide. The same gene region on chromosome 2
that was identified by this bipolar disorder and attempted
suicide study was recently identified by two complementary
family studies that looked at attempted suicide in families
with major depression and alcohol dependence.
"Family linkage studies are not always consistent, so
the fact that all three studies, including ours, point to
the same region of the genome is a good indication that we
are on the right track toward identifying a gene or genes
that play a role in why a person chooses to take his or her
own life," Willour said.
In the multi-institutional study, results of which
appear in the March issue of Biological Psychiatry,
the researchers examined data from 162 families with
bipolar disorder. They looked at attempted suicide in this
sample because it is an important clinical problem that
tends to occur more often in some of these families than in
others, suggesting a distinctive genetic basis, according
to senior author James B. Potash, of the Department of
Psychiatry. This technique of looking at sub-types of
illness is used by genetic researchers as a way to reduce
genetic complexity.
From the 162 families, the researchers selected 417
subjects who were diagnosed with schizoaffective/bipolar
disorder, bipolar I disorder or bipolar II disorder.
These subjects were asked whether they had ever
attempted suicide and the degree of intent of the most
serious attempt. One hundred fifty-four subjects said they
had attempted suicide, and 122 stated that they had
"definite" intent. For the purpose of this study, the
latter were considered to have a history of attempted
suicide.
Data for all 417 subjects was entered into a computer
program that looks for genetic similarities between
subjects with similar psychological profiles. Results
indicated that family members with a history of attempted
suicide and bipolar disorder showed a high degree of
genetic similarity at a specific area — DNA marker
D2S1777 — on a section of chromosome 2 referred to as
2p12. This is the same marker implicated in a 2004 study
from the University of Pittsburgh School of Medicine that
looked at attempted suicide and major depression. And it is
close to another marker, D2S1790, located in the 2p11
region of chromosome 2, that was identified in a 2004 study
from the University of Connecticut School of Medicine that
looked at alcoholism and attempted suicide.
Willour says that although the Johns Hopkins-led study
does not pinpoint a specific gene responsible for attempted
suicide, it does suggest a "neighborhood" in which the gene
might be found. She adds that the next step is to further
narrow the search and find the "address."
"Once we have located the specific gene," she said,
"we can better identify people who might be at risk of
suicide and offer drug companies a target for possible
therapies."
The data used by Willour and her team — DNA
samples, medical histories and psychiatric evaluations
— came from an independent study, CHIP, conducted at
the University of Chicago, Johns Hopkins and the National
Institute of Mental Health Intramural Program. The purpose
of CHIP, initiated in 1988 and funded through at least
2010, is to find genes that predispose people to developing
bipolar disorder or particular subtypes of the illness.
Other Johns Hopkins researchers who contributed to
this study are Peter P. Zandi, from the Department of
Mental Health in the Bloomberg School of Public Health; and
J. Raymond DePaulo Jr., Dean F. MacKinnon and Francis M.
Mondimore, from the Department of Psychiatry and Behavioral
Sciences in the School of Medicine. Additional researchers
include Elliot S. Gershon and Judith A. Badner, of the
University of Chicago; Francis J. McMahon, of the NIMH
Intramural Program; and Melvin G. McInnis, of the
University of Michigan, Ann Arbor. Funding for this study
came from the National Institute of Mental Health.