Posted by SLS on December 16, 2004, at 7:20:20
U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH
NIH News
National Institute of Mental Health (NIMH)
http://www.nimh.nih.gov/FOR IMMEDIATE RELEASE
Tuesday, December 14, 2004
MUTANT GENE LINKED TO TREATMENT-RESISTANT DEPRESSIONA mutant gene that starves the brain of serotonin, a mood-regulating
chemical messenger, has been discovered and found to be 10 times more
prevalent in depressed patients than in control subjects, report
researchers funded by the National Institutes of Health's National
Institute of Mental Health (NIMH) and National Heart Lung and Blood
Institute (NHLBI). Patients with the mutation failed to respond well to
the most commonly prescribed class of antidepressant medications, which
work via serotonin, suggesting that the mutation may underlie a treatment-
resistant subtype of the illness.The mutant gene codes for the brain enzyme, tryptophan hydroxylase-2, that
makes serotonin, and results in 80 percent less of the neurotransmitter.
It was carried by nine of 87 depressed patients, three of 219 healthy
controls and none of 60 bipolar disorder patients. Drs. Marc Caron,
Xiaodong Zhang and colleagues at Duke University announced their findings
in the January 2005 "Neuron," published online in mid-December."If confirmed, this discovery could lead to a genetic test for
vulnerability to depression and a way to predict which patients might
respond best to serotonin- selective antidepressants," noted NIMH Director
Thomas Insel, M.D.The Duke researchers had previously reported in the July 9, 2004 "Science"
that some mice have a tiny, one-letter variation in the sequence of their
tryptophan hydroxylase gene (Tph2) that results in 50-70 percent less
serotonin. This suggested that such a variant gene might also exist in
humans and might be involved in mood and anxiety disorders, which often
respond to serotonin selective reuptake inhibitors (SSRIs) --
antidepressants that block the re- absorption of serotonin, enhancing its
availability to neurons.In the current study, a similar variant culled from human subjects
produced 80 percent less serotonin in cell cultures than the common
version of the enzyme. More than 10 percent of the 87 patients with
unipolar major depression carried the mutation, compared to only one
percent of the 219 controls. Among the nine SSRI-resistant patient
carriers, seven had a family history of mental illness or substance abuse,
six had been suicidal and four had generalized anxiety.Although they fell short of meeting criteria for major depression, the
three control group carriers also had family histories of psychiatric
problems and experienced mild depression and anxiety symptoms. This points
up the complexity of these disorders, say the researchers. For example,
major depression is thought to be 40-70 percent heritable, but likely
involves an interaction of several genes with environmental events.
Previous studies have linked depression with the same region of chromosome
12, where the tryptophan hydroxylase-2 gene is located. Whether the
absence of the mutation among 60 patients with bipolar disorder proves to
be evidence of a different underlying biology remains to be investigated
in future studies.The researchers say their finding "provides a potential molecular
mechanism for aberrant serotonin function in neuropsychiatric disorders."Also participating in the study were: Raul Gainetdinov, Jean-Marin
Beaulieu, Tatyana Sotnikova, Lauranell Burch, Redford Williams, David
Schwartz, and Ranga Krishnan, Duke University.In addition to grants from NIMH and NHLBI, the study was also funded by
the Human Frontiers Science Program and the Canadian Institute of Health
Research.NIMH and NHLBI are part of the National Institutes of Health (NIH), the
Federal Government's primary agency for biomedical and behavioral
research. NIH is a component of the U.S. Department of Health and Human
Services.
poster:SLS
thread:430192
URL: http://www.dr-bob.org/babble/20041211/msgs/430192.html