The following is a summary of “Serotonin 4 Receptor Brain Binding in Major Depressive Disorder and Association With Memory Dysfunction,” published in the February 2023 issue of Psychiatry by Köhler-Forsberg, et al.

For a case-control study, researchers sought to investigate the neurobiological differences between antidepressant-free outpatients with moderate to severe major depressive disorder (MDD) and healthy controls. They examined the association between cerebral serotonin 4 (5-HT₄) receptor binding and cognitive functions in the depressed state. 

The study used baseline data from the NeuroPharm clinical depression trial in Denmark. All participants completed positron emission tomography (PET) scanning with [C]SB207145 to quantify brain 5-HT₄ receptor binding, but only the patients underwent cognitive testing. The study analyzed the group difference in cerebral 5-HT₄ receptor binding between patients with MDD and healthy controls and the association between 5-HT₄ receptor binding and verbal memory performance in the patient group, along with other cognitive domains (working memory, reaction time, emotion recognition bias, and negative social emotions) as secondary outcomes.

The study included 90 patients with untreated MDD (mean [SD] age, 27.1 [8.2] years; 64 women [71.1%]) and 91 healthy controls (mean [SD] age, 27.1 [8.0] years; 55 women [60.4%]). The study found that patients with current MDD had significantly lower cerebral 5-HT receptor binding than healthy controls (-7.0%; 95% CI, -11.2 to -2.7; P = .002). Additionally, in patients with MDD, there was a correlation between cerebral 5-HT₄ receptor binding and verbal memory (r = 0.29; P = .02). 

The study concluded that the lower cerebral 5-HT₄ receptor binding in patients with MDD was associated with memory dysfunction and that the cerebral 5-HT₄ receptor could be a promising treatment target for memory dysfunction in patients with MDD. The data analyses were performed from January 21, 2020, to April 22, 2022.

Source: jamanetwork.com/journals/jamapsychiatry/article-abstract/2801424