Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Pitt researchers find genes for depression; Play role in mood disorders, shorter lifespan

02.07.2003


Researchers at the University of Pittsburgh have completed the first survey of the entire human genome for genes that affect the susceptibility of individuals to developing clinical depression.



George S. Zubenko, M.D., Ph.D., professor of psychiatry at the University of Pittsburgh School of Medicine and adjunct professor of biological sciences at Carnegie Mellon University and his team have located a number of chromosomal regions they say hold the genetic keys to a variety of mental illnesses, including major depression and certain addictions. The survey was done in 81 families identified by individuals with recurrent, early-onset, major depressive disorder (RE-MDD), a severe form of depression that runs in families. The Pitt team’s findings are published today in the American Journal of Medical Genetics.

Finding the genetic roots of depression is important for many reasons. Depression is the second-leading cause of disability worldwide, affecting nearly 10 percent of the population. And while scientists have made significant progress developing new drugs to treat it, studies that identify specific risk genes may lead to even more effective drugs designed to target depression in specific individuals.


Twin studies have demonstrated that genetic factors typically account for 40 to 70 percent of the risk for developing major depression, but finding those genes has proven to be a challenge because, as in most diseases, there are likely numerous genes involved and only individuals with certain combinations of those genes develop the disorder.

Of equal interest is a secondary finding that – longevity in the families who carry these genes is significantly reduced.

The survey revealed 19 loci – small regions on chromosomes where genes reside – that appear to influence susceptibility to depressive disorders. The results extended the investigators’ previous finding that a small region of chromosome 2q containing the CREB1 gene affects the vulnerability of women to developing depression. And at least some of the 19 depression vulnerability loci appear to work in concert to affect a person’s risk of developing depression. According to Dr. Zubenko, "Greater scrutiny of the chromosome 2 locus has provided stronger evidence for the role of CREB1 as a risk gene for depressive disorders among women. In addition, five of the new genetic loci appear to interact with the CREB1 region to affect the risk of developing clinical depression in these families.

"Women are twice as likely as men to develop depression, and genetic differences appear to account for some of that disparity," said Dr. Zubenko. Sex-specific loci were common and preferentially affected the vulnerability of women to developing unipolar mood disorders. Evidence of at least one male-specific risk locus also was found. The sex-specific effects of particular risk genes for depression may result from the interactions of these genes and their products with sex hormones.

These findings suggest there are important differences in the molecular pathophysiology of mood disorders in men and women, or in the mechanisms that determine resistance to stressful stimuli. They may also help explain the vulnerability of women to depression during times of significant hormonal fluctuation including puberty, menstrual cycling, pregnancy and childbirth and menopause. Conversely, age-related reductions in hormone levels may contribute to a reduced proportion of familial cases of depression among depressions that arise later in life.

CREB1 is a gene that encodes a regulatory protein called CREB that orchestrates the expression of programs of other genes that play important roles in the brain and the rest of the body. The widespread importance of CREB as a genetic regulator may influence the development of additional psychiatric disorders related to depression, such as alcoholism and other addictions, as well as medical conditions outside of the nervous system that are associated with depression. For example, three of the new linkage regions affected the risk of developing a spectrum of depressive disorders including alcohol and other substance use disorders.

Remarkably, deceased members of the 81 families died at an age eight years younger than the general population and over 40 percent died before the age of 65. This difference in mortality was spread across the lifespan, including a five-fold increase in the proportion of children who died in the first year of life and several-fold increases in deaths by suicide, homicide and liver disease. However, most premature deaths occurred from "natural causes" including heart disease, cancer and stroke. "Tracking down the risk genes in these regions is an obvious priority, and we expect that the research will connect clinical depression and other medical disorders at their most fundamental levels," said Dr. Zubenko.

Information provided by the Human Genome Project is enabling the investigators to make important progress toward this goal. In 18 of the 19 newly identified genetic regions, the authors found candidate genes that participate in cell signaling pathways that converge on CREB. These observations provide an important new perspective on the biology of depression and its treatments that focuses on cell signaling pathways rather than particular neurotransmitters.

"The identification and characterization of susceptibility genes and their products will provide new opportunities for drug development and disease prevention, new information about the biology of mood and its regulation, and new insights into the interactions of mental illness and the human life span," said Dr. Zubenko. "Genotyping markers in chromosomal regions that harbor susceptibility genes may provide more immediate advances in the treatment of major depression. For example, individuals with particular genetic markers in these regions may respond better to particular current treatments than others. This strategy may enable clinicians to use genetic markers to better match individual patients to treatments to which they will optimally respond, while minimizing side effects."

Other researchers involved in this study include: Brion S. Maher, Ph.D.; Hugh B. Hughes III, M.S.; Wendy N. Zubenko, Ed.D., M.S.N..; J. Scott Stiffler, B.S.; Barry B. Kaplan, Ph.D.; and Mary L. Marazita, Ph.D.



The study received funding from the National Institute of Mental Health.
For more information on the Molecular Neurobiology and Genetics Lab at the University of Pittsburgh, please see http://www.zubenkolab.pitt.edu/.

CONTACT:
Craig Dunhoff
Jane Duffield
PHONE: 412-647-3555
FAX: 412-624-3184
E-MAIL: DunhoffCC@upmc.edu
DuffieldDJ@upmc.edu

Craig Dunhoff | EurekAlert!
Further information:
http://www.upmc.edu/

More articles from Life Sciences:

nachricht A Varied Menu
25.03.2019 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht Key evidence associating hydrophobicity with effective acid catalysis
25.03.2019 | Tokyo Metropolitan University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The taming of the light screw

DESY and MPSD scientists create high-order harmonics from solids with controlled polarization states, taking advantage of both crystal symmetry and attosecond electronic dynamics. The newly demonstrated technique might find intriguing applications in petahertz electronics and for spectroscopic studies of novel quantum materials.

The nonlinear process of high-order harmonic generation (HHG) in gases is one of the cornerstones of attosecond science (an attosecond is a billionth of a...

Im Focus: Magnetic micro-boats

Nano- and microtechnology are promising candidates not only for medical applications such as drug delivery but also for the creation of little robots or flexible integrated sensors. Scientists from the Max Planck Institute for Polymer Research (MPI-P) have created magnetic microparticles, with a newly developed method, that could pave the way for building micro-motors or guiding drugs in the human body to a target, like a tumor. The preparation of such structures as well as their remote-control can be regulated using magnetic fields and therefore can find application in an array of domains.

The magnetic properties of a material control how this material responds to the presence of a magnetic field. Iron oxide is the main component of rust but also...

Im Focus: Self-healing coating made of corn starch makes small scratches disappear through heat

Due to the special arrangement of its molecules, a new coating made of corn starch is able to repair small scratches by itself through heat: The cross-linking via ring-shaped molecules makes the material mobile, so that it compensates for the scratches and these disappear again.

Superficial micro-scratches on the car body or on other high-gloss surfaces are harmless, but annoying. Especially in the luxury segment such surfaces are...

Im Focus: Stellar cartography

The Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI) at the Large Binocular Telescope (LBT) in Arizona released its first image of the surface magnetic field of another star. In a paper in the European journal Astronomy & Astrophysics, the PEPSI team presents a Zeeman- Doppler-Image of the surface of the magnetically active star II Pegasi.

A special technique allows astronomers to resolve the surfaces of faraway stars. Those are otherwise only seen as point sources, even in the largest telescopes...

Im Focus: Heading towards a tsunami of light

Researchers at Chalmers University of Technology and the University of Gothenburg, Sweden, have proposed a way to create a completely new source of radiation. Ultra-intense light pulses consist of the motion of a single wave and can be described as a tsunami of light. The strong wave can be used to study interactions between matter and light in a unique way. Their research is now published in the scientific journal Physical Review Letters.

"This source of radiation lets us look at reality through a new angle - it is like twisting a mirror and discovering something completely different," says...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International Modelica Conference with 330 visitors from 21 countries at OTH Regensburg

11.03.2019 | Event News

Selection Completed: 580 Young Scientists from 88 Countries at the Lindau Nobel Laureate Meeting

01.03.2019 | Event News

LightMAT 2019 – 3rd International Conference on Light Materials – Science and Technology

28.02.2019 | Event News

 
Latest News

Laser processing is a matter for the head – LZH at the Hannover Messe 2019

25.03.2019 | Trade Fair News

A Varied Menu

25.03.2019 | Life Sciences

‘Time Machine’ heralds new era

25.03.2019 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>