People who suffer from depression may have far fewer of the receptors in the brain that regulate our happiness when compared to non-depressed people. The new study also suggests that the fewer receptors a person has, the more severe their depression.
Scans show untreated depressed people have fewer serotonin and opioid receptors, and that variation is linked to symptoms and treatment response. But the research also showed the numbers of these receptors can vary greatly from person to person.
The lead University of Michigan researcher, Jon-Kar Zubieta, M.D., Ph.D., says these new results bolster what other researchers have been finding in recent years.
“There’s a substantial amount of biological difference even among people who have major depression, which is just as important as the biological differences between people with depression and people without,” he says.
“The more we can understand about these differences, the better we can address treatment to the individual and have the greatest effect on symptoms.”
Zubieta presented data from positron emission tomography, or PET, scans of the brains of patients who met the criteria for major depression but had not yet received treatment for it.
Those scans were compared with scans of the brains of non-depressed comparison volunteers.
In one group of depressed and non-depressed volunteers, the scans were made using a tracer that can reveal the location and concentration of a particular type of receptor. Called the 5HT1a receptor, it allows brain cells to receive signals from serotonin, a chemical neurotransmitter produced by the brain.
Serotonin levels in the brain are linked to depression, but the importance of 5HT1a receptor concentrations in the brains of depressed people has been cloudy. That’s why Zubieta’s team chose to scan only people who had not yet received antidepressant medications, since some such medications may actually encourage the brain’s cells to make more serotonin receptors — and masking the actual level of receptors that the person has naturally.
In the study, 5HT1a receptor concentrations were markedly lower in depressed people compared with non-depressed people, in both the left and right hippocampus region of the brain.
But even among depressed people, the lower a person’s the 5HT1 receptor levels were, the worse he or she scored on assessments of their ability to function day-to-day. They were also less likely to get relief from symptoms when the researchers prescribed a common antidepressant.
This finding of individual variation may help explain why some patients find great relief from a medication that doesn’t help other equally depressed patients, says Zubieta.
The other group of depressed and non-depressed volunteers received PET scans with a tracer that allowed the researchers to see the mu-opioid receptors (which bind endorphins) in their brains. These receptors are the gateway for signals sent by chemicals which are involved in stress response including response to pain.
In this group of depressed and non-depressed volunteers, the researchers studied the distribution of the mu-opioid receptors and looked at how active the receptors were when the volunteers were asked to summon a sad memory or scenario to mind.
Depressed volunteers had lower concentrations of mu-opioid receptors to begin with. But when they underwent the “sadness challenge”, those receptors were much more active than the receptors in non-depressed people. And, just as with the serotonin 5HT1a receptors, the fewer mu-opioid receptors a person had, the less well they responded to an antidepressant medication.
Zubieta and his colleagues are now working to submit these new data for publication. At the same time, they are continuing to recruit depressed volunteers who are not taking medication for more brain imaging studies.
It is not clear whether the results of this small study are generalizeable to a broader population. Further research needs to be conducted to answer this question.
The preliminary findings were presented at the American Psychiatric Association’s annual meeting in Washington, D.C. in 2008.
Source: University of Michigan’s Depression Center