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.
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!
Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München
Second research flight into zero gravity
21.10.2016 | Universität Zürich
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.
Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
21.10.2016 | Health and Medicine
21.10.2016 | Information Technology
21.10.2016 | Materials Sciences