A recent study is providing some new information in the ongoing effort to unravel the mystery of depression treatment. Suggesting that antidepressants may be altering brain chemistry in ways other than merely improving mood. In patients with Major Depressive Disorder (MDD), researchers are now concentrating on a particular serotonin receptor called 5-HT4R, and the results are really startling.
It has long been known that untreated depression is associated with reduced levels of the 5-HT4 receptor in the brain. Which has been connected to cognitive problems, particularly verbal memory problems. However, after antidepressant treatment begins, what happens to these receptors? Could they be the key to more targeted treatments for the cognitive effects of depression, or do they just adjust to the medication?
Before beginning treatment with escitalopram, a kind of selective serotonin reuptake inhibitor (SSRI), 90 patients with moderate to severe major depressive disorder (MDD) had molecular brain imaging to measure their 5-HT4 receptor levels. By weeks eight or twelve, the researchers hoped to determine whether these initial receptor levels might predict who would react favorably to the drug.
Remarkably, the initial receptor levels did not accurately indicate who would do well. However, things became fascinating when 40 of the patients underwent rescans after eight weeks of treatment. According to the study, there was a 9% decrease in 5-HT4 receptor levels in the neostriatum, which is the area of the brain responsible for motor and cognitive processes. This is in line with the theory that SSRIs reduce depression symptoms by increasing extracellular serotonin levels in the brain. That isn’t the whole tale, though.
Interestingly, whereas verbal memory improvements were associated with this change in receptor activity, overall improvements in depressed symptoms as assessed by the Hamilton Depression Rating Scale (HAMD6) did not correspond with this change. In other words, even while people’s emotional states weren’t getting substantially better or at all, the SSRI medication appeared to improve their cognitive abilities.
Even more perplexing is the fact that verbal memory improved most in patients whose 5-HT4 receptors changed the least following treatment. This implies that the stronger the cognitive function, the more stable the receptor levels remained following treatment. It is somewhat paradoxical, but it may pave the way for novel therapeutic approaches that precisely target these receptors to improve cognitive function in all moods.
The researchers draw the conclusion that the 5-HT4 receptor may be a target for more specialized treatment approaches for Major Depressive Disorder, and that the results provide intriguing hints about how antidepressants function. However, additional research is required to fully understand these intricate relationships, as is the case with all brain research.
This study emphasizes how crucial it is to take cognitive symptoms, such as memory issues, into account when considering treatment, even though depression is typically thought of as a mood illness. Furthermore, since SSRIs are being used by an increasing number of individuals worldwide to treat depression, discoveries such as these may contribute to the development of more accurate, efficient, and possibly even faster treatments.
The 5-HT4 receptor may ultimately be the key to treating the cognitive problems associated with depression, even if it may not be able to anticipate who would experience a positive change in mood. This paves the way for more research and, perhaps, therapies that target particular receptors to enhance not only our emotions but also our cognitive abilities.
This research was published in Biological Psychiatry.
