Serotonin Receptors: The Key to Better Mood and Memory

Serotonin, also known as the "feel-good" hormone, plays an important role in improving our mood and easing depression. Researchers have discovered that SSRI (Selective Serotonin Reuptake Inhibitors) antidepressants, specifically escitalopram, may help boost certain cognitive abilities like verbal memory. The brain contains multiple serotonin receptors that help regulate mood by managing serotonin levels.

They studied brain activity in patients before and after taking the drug, finding that improvements in cognition were linked to a reduction in a specific serotonin receptor in the brain (1^✔ ✔Trusted Source
Effect of antidepressant treatment on 5-HT4 receptor binding and associations with clinical outcomes and verbal memory in major depressive disorder

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How SSRI Antidepressants Help Mood and Memory

The research focused on the receptor type, known as 5HT4. The study results were recently shared at the ECNP Conference in Milan and published in Biological Psychiatry. The researchers began by scanning the brains of 90 depressed patients, to measure the quantity of 5HT4 receptors to which serotonin binds. At the same time, patients were given a series of tests to measure mood and cognitive abilities.

Patients were given daily doses of escitalopram, and at the end of 8 weeks, 40 patients were rescanned to measure the quantity of 5HT4 receptors in the brain. The mood of the patients had improved, but the team also found that the levels of the 5HT4 receptor had dropped by around 9% possibly due to adaptations to increased levels of serotonin.

When they asked these patients to undertake more cognitive tests, they found that their performance had improved, so that the less the 5HT4 receptor had changed the better the cognitive outcome. This phenomenon was particularly prominent for the ability to recall words.

“This is potentially significant,” said researcher Vibeke Dam (Copenhagen University Hospital, Rigshospitalet, Denmark), “It seems that the SSRI medication contributes to an improvement in cognitive function, at the same time as helping improve mood.

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Our work ties the improvement in cognitive function to the specific 5HT4 receptor and suggests that direct serotonin 4 receptor stimulation may be an important pro-cognitive target to consider in optimizing outcomes of antidepressant treatment. It also reinforces the idea that serotonin is crucial to mood improvement.

Exploring 5HT4 Receptors for Better Thinking

Co-researcher Vibe Froekjaer (Copenhagen University Hospital, Rigshospitalet, Denmark), added, “This is a first result, so we need to do a lot more work to look at the implications. Poor cognitive function is very hard to treat efficiently and may require extra treatment. This work points to the possibility of stimulating this specific receptor so that we can treat cognitive problems, even aside from whether or not the patient has overcome the core symptoms of depression”.

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The researchers note that this was a real-world study, so there is no placebo control.

The team’s next step is to treat patients with drugs that specifically stimulate the 5HT4 receptor to see the effect on cognitive function; interestingly, serotonin is also found in the gut, and there are drugs available to treat irritable bowel syndrome that specifically bind to and stimulate 5HT4, which the team may repurpose in these trials.

Reference:

1. Effect of antidepressant treatment on 5-HT4 receptor binding and associations with clinical outcomes and verbal memory in major depressive disorder - (https:www.biologicalpsychiatryjournal.com/article/S0006-3223(24)01537-3/abstract)

Source-Eurekalert