Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers discover possible markers for mental illness

04.12.2007
Researchers have discovered natural genetic differences that might help predict the most effective antipsychotic drugs for particular patients with mental disorders such as schizophrenia, Parkinson’s and drug addiction.

They found the differences in the gene for a molecule called the dopamine D2 receptor (DRD2), a protein present on brain cells that are sensitive to the neurotransmitter dopamine.

The receptor is known to play a key role in memory and in a variety of mental illnesses. Most antipsychotic drugs work at least in part by blocking this protein, but scientists don’t yet understand how this helps patients. Nor can they explain why some people respond well to certain antipsychotic drugs and others respond poorly.

“Our study shows that these differences affect normal brain activity and memory processing, and therefore may also be important in mental illness,” says principal investigator Wolfgang Sadee, program director in pharmacogenomics at the Ohio State University Medical Center.

... more about:
»DRD2 »RNA »SNP »Sadee »activity »antipsychotic »differences »markers

The findings could lead to tests that will enable doctors to match patients with certain mental illnesses to the most effective therapy, something they cannot do now.

The study was done in collaboration with Professor Alessandro Bertolino, University of Bari, Italy, who performed the clinical research. It is published online in the Proceedings of the National Academy of Sciences.

“Identifying these predictive markers is important because antipsychotic drugs are effective in only a portion of patients upon first treatment, and it takes a month or more to establish their efficacy,” says Sadee, who is also a professor of psychiatry and chair of the department of pharmacology.

“During this time, irreparable damage can result if the wrong antipsychotic is given to a patient.”

Sadee notes that the D2 receptor gene has been implicated in mental illness for some time, but that a variety of clinical studies have failed to consistently link variations in the gene to disease.

These findings may change that.

For this study, Sadee and his colleagues analyzed 68 autopsy samples of normal human brain tissue. For each case, the researchers measured and compared the amount of messenger RNA made by each of the two copies of the DRD2 gene. Messenger RNA is a molecule made when a gene is involved in making its protein.

In 15 of the 68 cases, the relative amounts of messenger RNA made by one gene in the pair was strikingly different from the amount made by the other. The disparity was a clue that something was different between the genes.

Comparisons of these DRD2 genes to the rest revealed three small differences in the DNA called single-nucleotide polymorphisms, or SNPs (pronounced ‘snips’).

SNPs are tiny natural variations between individuals that occur at certain positions in genes, providing landmarks in the genome.

SNPs often have no effect on the function of the gene or its protein, but, in this case, laboratory experiments showed that particular changes in two of the SNPs alters how the messenger RNA for DRD2 is processed.

That, in turn, changed the relative amounts of two variants of the protein that are made by the gene.

“The two variants of DRD2 have distinct functions, facilitating or inhibiting dopaminergic transmission, so that a change in their ratios is potentially critical,” Sadee says. “We believed that this change would enhance dopamine activity in the brain.”

The researchers then tested this hypothesis in normal human volunteers who took simple memory performance tests. The participants’ brain activity was monitored during the testing by functional magnetic resonance imaging (fMRI).

The results showed that volunteers with the two variant SNPs had significantly more brain activity than the usual SNPs for the same memory task.

“Their brain needed to ‘work’ more to get the same result,” Sadee says. The two SNPs were also associated with reduced memory performance and attentional control.

Sadee and his colleagues are now testing the relevance of the SNP markers in patients with schizophrenia and in patients with cocaine addiction.

Darrell E. Ward | EurekAlert!
Further information:
http://www.osumc.edu

Further reports about: DRD2 RNA SNP Sadee activity antipsychotic differences markers

More articles from Life Sciences:

nachricht Rutgers scientists discover 'Legos of life'
23.01.2018 | Rutgers University

nachricht Researchers identify a protein that keeps metastatic breast cancer cells dormant
23.01.2018 | Institute for Research in Biomedicine (IRB Barcelona)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Optical Nanoscope Allows Imaging of Quantum Dots

Physicists have developed a technique based on optical microscopy that can be used to create images of atoms on the nanoscale. In particular, the new method allows the imaging of quantum dots in a semiconductor chip. Together with colleagues from the University of Bochum, scientists from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute reported the findings in the journal Nature Photonics.

Microscopes allow us to see structures that are otherwise invisible to the human eye. However, conventional optical microscopes cannot be used to image...

Im Focus: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Rutgers scientists discover 'Legos of life'

23.01.2018 | Life Sciences

Seabed mining could destroy ecosystems

23.01.2018 | Earth Sciences

Transportable laser

23.01.2018 | Physics and Astronomy

VideoLinks Science & Research
Overview of more VideoLinks >>>