Low levels of serotonin in the brain are thought to be a possible cause of depression, and many antidepressants work by blocking a protein that carries serotonin away from 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 serotonergic system are part of the biology of depression and that this change is related to the episode rather than a static characteristic – a condition rather than a trait,” explains the latest author of Johan Lundberg study, researcher. at the Department of Clinical Neurosciences, Karolinska Institutet. “The discovery raises many questions about the function of the serotonin system in depression and opens up avenues of research that could challenge the dominant concept of serotonin and depression.”
Serotonin is a neurotransmitter that affects mood and emotions, among other things. Its transporter protein, 5-HTT, is believed to play a critical role in depression because it pumps serotonin away from brain neuron synapses, thereby regulating the amount of active serotonin in the brain.
Many modern antidepressants inhibit this transporter, which increases the concentration of serotonin in synapses. However, the effect of these drugs can be delayed for several weeks, and in some cases they have no effect at all, so there is an urgent need for new or improved drug therapies. 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 individuals. This finding is somewhat surprising given the dominant theory of the function of serotonin 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 the concentration of serotonin, high levels of the protein can be expected in depressed people. To better understand these results, a longitudinal or post-treatment 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, the researchers set out to investigate how the serotonin transporter changes when a depressed person is successfully treated. To do this, they measured the levels of 5-HTT in 17 people with depression before and after an internet cognitive behavioral therapy course. The measurements were performed 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% higher after three months of treatment, when 13 of 17 patients reported significant improvement in their symptoms. Before treatment, people with depression had roughly the same average level of 5-HTT as a control group of 17 healthy people.
“Instead of lower serotonin transporter levels when depression was treated, we found the opposite – more transporter after symptom improvement,” says Jonas Svensson, postdoctoral researcher in Dr. Lundberg’s group. “One possible interpretation is that the serotonergic system does not cause depression but is part of the brain’s defense mechanism to protect against depression. One could hypothesize, for example, that the level of 5-HTT decreases when an individual is under stress, such as during a depressive state, and that the level rises or normalizes when this stress disappears. It is important to point out, however, that although these ideas are raised by our study, its design does not allow us to conclude on why 5-HTT levels are changing. “
The study had some limitations, such as it only included 17 people with depression, which is a heterogeneous condition, and the control group was only examined once. Researchers are currently designing new studies to test whether the dynamic function of the serotonergic system can be part of a stress defense system.
Source of the story:
Material provided by Karolinska Institute. Note: Content can be changed for style and length.