(Great Neck, N.Y. - May 14, 2009) — The long-held view that levels of the neurotransmitter serotonin are low in people with depression has now been challenged by NARSAD Distinguished Investigator Philip Cowen, M.D., professor of psychopharmacology at Oxford University.

Reporting at the British Neuroscience Association meeting in Liverpool on April 21, Dr. Cowan said: "We asked what evidence is there that the action is abnormal, and this stimulated new thinking about how antidepressants work."

Research in rats has shown that antidepressants, such as SSRIs (selective serotonin reuptake inhibitors) or SNRIs (selective norepinephrine reuptake inhibitors), elevate serotonin levels in the brain, leading to a series of brain changes. This cascade of biochemical events can be measured, but less well-documented are the psychological effects: how people handle their emotions and how this might translate into improved subjective mood.

"When people are depressed, they have a bias toward negative responses and feelings. They may feel, for example, that their work colleagues are hostile toward them, creating a downward spiral of misery and anxiety," Cowen said.

In a recent, randomized double-blind study, 42 healthy men and women who did not have depression were given antidepressants (SSRIs or SNRIs) or a placebo for seven days. After a few days of treatment with SSRIs, they became more positive in their emotional outlook based on performance on tasks of emotional processing. These positive biases in emotional processing were independent of their reported mood.

"The drugs work quickly to change how people experience the world emotionally. We believe this is due to the effect of the drugs on emotional processing, rather than directly altering mood. Remembering and experiencing events in a more positive light helps to lift a person out of their depression," Cowen said.

This mechanism of the action of antidepressants is compatible with cognitive behavioral therapy, suggesting that this dual approach will be helpful for people with depression.