Brain Imaging Research Annual Report 2005

Jeff Meyer:

Brain imaging to help develop new antidepressant medications

To make progress in our understanding of depression and antidepressant treatment, we need to better understand the balance and functions of chemicals in the brain, such as serotonin, that play a role in mood disorders.

Dr. Jeff Meyer, Head of Neurochemical Imaging in Mood Disorders at the PET Centre, is working to understand depression using positron emission tomography (PET). PET is  a "brain scan" procedure that allows us to measure proteins and chemicals in the brain. Dr. Meyer is using a new PET technique developed in Toronto to measure serotonin transporters.

Serotonin transporters, located on the ends of nerves, are sites that remove serotonin from active areas to inactive areas. In short, they control serotonin levels in active areas of the brain. Key questions about these sites needed to be answered: Are there more or fewer  serotonin transporter sites during depression? How much do antidepressants affect these sites to change serotonin levels?

"In the past, most treatments for depression were found with a lot of luck," says Dr. Meyer. "To advance in the future, we need to better under-stand the details of the illness and treatments."

Two recent studies illustrate the way  Dr. Meyer's work will help generate future treatments and allow for more effective  prescribing today.

The first question Dr. Meyer asked was whether the amount of serotonin transporter is changed in the brain of people who are depressed.

In the December 2004 issue of the Archives of General Psychiatry, Dr. Meyer and colleagues reported on his study of serotonin transporters in the brain of people living with depression. In this study, they found that when serotonin transporters are elevated by about 25 per cent in people with depression, they develop symptoms of severe pessimism.

This project helps us better understand the complexity of how brain chemicals and the serotonin transporter are involved and altered in depression.

In the second study, Dr. Meyer used this PET approach to measure the percentage of brain serotonin transporter sites that are typically blocked by antidepressant medications. This measurement, it was hoped, would help us see how frequently prescribed medications affect the serotonin transporter.

In the May 2004 issue of the American Journal of Psychiatry, he reported that 80 per cent of serotonin transporter sites are blocked by the lowest therapeutic dose of the five most common antidepressants.

The long-term benefit will be to improve our understanding of how these antidepressants work. For example, one can see by these two studies that antidepressants that target the serotonin transporter do more than just balance serotonin-treatment lowers the measure by at least 80 per cent, and the measure is raised  in depression at most by 25 per cent.

The short-term benefit of this information is that clinicians can better tailor the dose of antidepressant drugs to meet individual needs. Choosing the right dose for some could mean lessened side effects; for others, it could mean getting a better response. Another short-term benefit is that Dr. Meyer's results are now the industry standard for developing new antidepressant treatments.

Eighty per cent of serotonin transporter sites are blocked by the lowest  therapeutic dose of the five most common antidepressants.

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