Brain serotonin transporter is associated with cognitive‐affective biases in healthy individuals

Abstract

Cognitive affective biases describe the tendency to process negative information or positive information over the other. These biases can be modulated by changing extracellular serotonin (5‐HT) levels in the brain, for example, by pharmacologically blocking and downregulating the 5‐HT transporter (5‐HTT), which remediates negative affective bias. This suggests that higher levels of 5‐HTT are linked to a priority of negative information over positive, but this link remains to be tested in vivo in healthy individuals. We, therefore, evaluated the association between 5‐HTT levels, as measured with [ 11 C]DASB positron emission tomography (PET), and affective biases, hypothesising that higher 5‐HTT levels are associated with a more negative bias. We included 98 healthy individuals with measures of [ 11 C]DASB binding potential (BP ND ) and affective biases using The Emotional Faces Identification Task by subtracting the per cent hit rate for happy from that of sad faces (EFIT AB ). We evaluated the association between [ 11 C]DASB BP ND and EFIT AB in a linear latent variable model, with the latent variable (5‐HTT LV ) modelled from [ 11 C]DASB BP ND in the fronto‐striatal and fronto‐limbic networks implicated in affective cognition. We observed an inverse association between 5‐HTT LV and EFIT AB ( β = −8% EFIT AB per unit 5‐HTT LV , CI = −14% to −3%, p = .002). These findings show that higher 5‐HTT levels are linked to a more negative bias in healthy individuals. High 5‐HTT supposedly leads to high clearance of 5‐HT, and thus, a negative bias could result from low extracellular 5‐HT. Future studies must reveal if a similar inverse association exists in individuals with affective disorders.

Genetic contributions to brain serotonin transporter levels in healthy adults

“…Data included in the current study has been utilized in previous studies 9 , 10 , 23 , 45 , 47 , some of which focused on the relation between 5-HTTLPR and/or BDNF rs6265 [ 11 C]DASB binding 23 , 45 .…”

“…Previous research has reported a link between 5-HTT levels and both healthy and pathological behavioral phenotypes. Increased 5-HTT availability (expressed in terms of binding potential, 5-HTT BP) has been linked to depressive symptoms severity in seasonal affective disorder 9 , greater negative affective bias 10 , 11 and reduced amygdala reactivity to threat in healthy individuals 12 , 13 , whereas low 5-HTT availability has been associated with childhood abuse in patients with depression vs patients who did not experience childhood abuse 14 . Notably, some studies have speculated that 5-HTT availability may be used as a marker of serotonin tone and a histochemical marker for serotonergic projections 15 , 16 .…”

Lasting increases in trait mindfulness after psilocybin correlate positively with the mystical-type experience in healthy individuals

“…Neocortical (a volume-weighted average of all cortical regions) [ 11 C]-Cimbi-36 BP ND was chosen as our primary outcome region based on findings from our previous study ( Madsen et al, 2020 ), the high expression of 5-HT 2A R within neocortex ( Beliveau et al, 2017 ) and the high degree of inter-regional correlation across neocortical subregions ( Erritzoe et al, 2010 ; Spies et al, 2020 ). As secondary outcomes for post-hoc analyses, [ 11 C]-Cimbi-36 BP ND in frontolimbic regions [frontal cortex, left and right amygdala and left and right anterior cingulate cortex (ACC)] were chosen based on a previous study ( Armand et al, 2022 ).…”