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Dr. Paul Albert's group is investigating how a common genetic mutation could lead to depression



Major depression will affect about 16 percent of people at some point in life, but Dr. Paul Albert’s neuroscience group has shown that some are at greater risk than others. They found that people with a genetic mutation in a serotonin receptor gene were twice as likely to suffer from depression, four times as likely to commit suicide and less likely to respond to common anti-depressants. Their latest research, published in the Journal of Neuroscience in February, reveals why, and also says something about how the normal brain works.

“Depression is often associated with reduced levels of the neurotransmitter serotonin or decrease in receptors that mediate serotonin action,” said Dr. Albert. Normally, cells that send serotonin signals tend to have lower serotonin receptor gene activity than cells that receive the signals. But the mutation that Dr. Albert found reverses this relationship – resulting in higher serotonin receptor gene activity in the sending cells and lower activity in the receiving cells, and increasing the likelihood of depression.

“We found that a single factor called Deaf-1 controls this differential regulation of serotonin activity; but Deaf-1 can’t bind to the mutant gene, so serotonin gene activity gets reversed in the two cell types,” said Dr. Albert.

The work is a milestone in depression research and neuroscience in general, and may lead to new approaches to detect and treat depression.

Dr. Albert is a Senior Scientist in the Neuroscience program at the Ottawa Hospital Research Institute and a Professor in the Faculty of Medicine at the University of Ottawa. This research was supported by the Canadian Institutes of Health Research.