KAROLINSKA INSTITUTE
Low levels of serotonin in the brain are considered a possible cause of depression, and many antidepressants work by blocking a protein that transports serotonin out of nerve cells. A brain imaging study at Karolinska Institutet now shows that the average level of the serotonin transporter increased in a group of 17 people who recovered from depression after cognitive behavioral therapy. The results are published in the journal Translational Psychiatry .
"Our results suggest that changes in the serotonin system are part of the biology of depression and that this change is related to the episode rather than a static characteristic, a state rather than a trait," says the last author of the study, Johan Lundberg, researcher at the Department of Clinical Neuroscience, Karolinska Institutet. "The finding raises many questions about the role of the serotonin system in depression and opens lines of research that could challenge the prevailing concept of serotonin and depression."
Serotonin is a neurotransmitter that affects, among other things, mood and emotions. Its transporter protein, 5-HTT, is considered to play a fundamental role in depression, as it pumps serotonin from the synapses of brain neurons, thus regulating the amount of active serotonin in the brain.
Many modern antidepressant drugs inhibit this transporter, increasing the concentration of serotonin at the synapses. However, the effect of these medications can be delayed by several weeks and, in certain cases, have no effect at all, making the need for new or improved drug therapies urgent. To achieve this, more knowledge is needed about the biological causes of the disease.
Previous studies have shown that depressed people have lower levels of 5-HTT in the brain than healthy people. This finding is somewhat surprising given the dominant theory of serotonin’s role in depression, "the serotonin hypothesis . " This theory dictates that low levels of synaptic serotonin cause depressive symptoms, and since the function of 5-HTT is to reduce serotonin concentration, high levels of the protein might be expected in depressed individuals. To better understand these findings, a post-treatment or longitudinal study design can be used to answer the question of whether 5-HTT is temporarily or chronically low in people with depression.
In this study, researchers sought to investigate how the serotonin transporter changes when a depressed person is successfully treated.
To do this, they measured 5-HTT levels in 17 people with depression before and after a course of Internet-based cognitive behavioral therapy . The measurements were achieved with positron emission tomography (PET), a brain imaging technique in which scientists can measure the levels of different substances in the brain using radioactive tracers.
The researchers found that 5-HTT levels were on average 10 percent higher after three months of treatment, when 13 of the 17 patients reported a significant improvement in their symptoms. Before treatment, individuals with depression had approximately the same average 5-HTT level as a control group of 17 healthy individuals.
"Instead of lower serotonin transporter levels when depression had been treated, we found the opposite: more transporter after symptom improvement," says Jonas Svensson, a postdoctoral researcher in Dr. Lundberg’s group. "One possible interpretation is that the serotonin system does not cause depression, but is part of the brain’s defense mechanism to protect against depression. One could assume, for example, that the level of 5-HTT drops when an individual is subjected to stress, such as during a depressive state, and that the level increases or normalizes when this stress disappears. However, it is important to note that even if these ideas are raised by our study, its design does not allow us to draw any conclusions about why 5-HTT levels change."
The study had some limitations, such as that it only included 17 people with depression, which is a heterogeneous condition, and that the control group was examined only once. Researchers are now designing new studies to test whether the dynamic function of the serotonin system may be part of a stress defense system.
