Brain serotonin 4 receptor binding is inversely associated with verbal memory recall

We have previously identified an inverse relationship between cerebral serotonin 4 receptor (5-HT ₄R) binding and nonaffective episodic memory in healthy individuals. Here, we investigate in a novel sample if the association is related to affective components of memory, by examining the association between cerebral 5-HT ₄R binding and affective verbal memory recall.

Twenty-four healthy volunteers were scanned with the 5-HT ₄R radioligand [¹¹C]SB207145 and positron emission tomography, and were tested with the Verbal Affective Memory Test-24. The association between 5-HT ₄R binding and affective verbal memory was evaluated using a linear latent variable structural equation model.

We observed a significant inverse association across all regions between 5-HT ₄R binding and affective verbal memory performances for positive (p = 5.5 × 10^-4) and neutral (p = .004) word recall, and an inverse but nonsignificant association for negative (p = .07) word recall. Differences in the associations with 5-HT ₄R binding between word categories (i.e., positive, negative, and neutral) did not reach statistical significance.

Our findings replicate our previous observation of a negative association between 5-HT ₄R binding and memory performance in an independent cohort and provide novel evidence linking 5-HT ₄R binding, as a biomarker for synaptic 5-HT levels, to the mnestic processing of positive and neutral word stimuli in healthy humans.