Serotonin 4 receptor brain binding and oxytocin-promoted affective and social cognition in healthy women – A randomized controlled trial

Background: Oxytocin is a neuropeptide known for its prosocial properties and role in social bonding, and intervention with intranasal oxytocin is posited to modulate affective and social cognition (i.e., hot cognition). Serotonin (5-HT) neurotransmission is also involved in emotional and social behaviors and appear to work in concert with oxytocin. However, this interaction so far remains elusive in humans. Therefore, we here investigate the relation between brain 5-HT 4 receptor (5-HT4R) levels and oxytocin-modulated hot cognition. Methods: Using a double blind, placebo-controlled, randomized crossover design, 35 healthy women received a dose of 24 IU intranasal oxytocin or placebo one month apart. The women were naturally cycling and to control for hormonal fluctuations across the menstrual cycle, intervention days were placed during the early follicular phase. Following intervention cognitive domains including affective memory, affective bias in emotion processing, moral emotions and social information preference were assessed. In a subgroup (n = 25), Positron Emission Tomography (PET) was used to image 5-HT4R brain binding at baseline with the [11C]SB207145 radiotracer. Results: No effect of oxytocin intervention relative to placebo was observed for any of the cognitive outcomes. Likewise, regional brain 5-HT4R binding at baseline was not associated with cognitive responses to oxytocin intervention. Conclusion: Our data suggest that intervention with intranasal oxytocin does not have an overall effect on hot cognition in healthy women and further that 5-HT4R brain architecture does not mediate cognitive effects of oxytocin in the healthy state

No evidence for a role of the serotonin 4 receptor in five-factor personality traits: A positron emission tomography brain study

<div><p>Serotonin (5-HT) brain architecture appears to be implicated in normal personality traits as supported by genetic associations and studies using molecular brain imaging. However, so far, no studies have addressed potential contributions to variation in normal personality traits from <i>in vivo</i> serotonin 4 receptor (5-HT₄R) brain availability, which has recently become possible to image with Positron Emission Tomography (PET). This is particularly relevant since availability of 5-HT₄R has been shown to adapt to synaptic levels of 5-HT and thus offers information about serotonergic tone in the healthy brain. In 69 healthy participants (18 females), the associations between personality traits assessed with the five-factor NEO Personality Inventory-Revised (NEO PI-R) and regional cerebral 5-HT₄R binding in neocortex, amygdala, hippocampus, and anterior cingulate cortex (ACC) were investigated using linear regression models. The associations between each of the five personality traits and a latent variable construct of global 5-HT₄R levels were also evaluated using latent variable structural equation models. We found no significant associations between the five NEO personality traits and regional 5-HT₄R binding (all <i>p</i>-values > .17) or the latent construct of global 5-HT₄R levels (all <i>p</i>-values > .37). Our findings indicate that NEO personality traits and 5-HT₄R are not related in healthy participants. Under the assumption that global 5-HT₄R levels index 5-HT tone, our data also suggest that 5-HT tone per se is not directly implicated in normal personality traits.</p></div

NEO personality and regional 5-HT₄R binding potential.

<p>NEO personality and regional 5-HT₄R binding potential.</p

Descriptive data.

<p>Descriptive data.</p

Schematic overview of the latent variable model for the association between cerebral serotonin 4 receptor (5-HT₄R) binding potential (BP_ND) and NEO personality traits.

<p>A separate model was determined for each of the five NEO personality traits: Neuroticism, Extroversion, Openness, Agreeableness and Conscientiousness. The circle represents the latent 5-HT₄R variable (LV_u). Light gray boxes indicate observed predictors and the dark gray boxes, predicted by the latent variable, represent observed log-transformed regional 5-HT₄R BP_ND and NEO personality trait. Age, gender, and BDNF val66met genotype all map directly onto the latent variable (LV_u). Age and sex also predict the personality trait and 5-HTTLPR genotype predicts neocortex regional BP_ND only. Not shown in the model are two observed predictors 1) scanner type (GE-Advance vs. HRRT PET scanner) and 2) weight adjusted injected mass, which map directly onto each regional BP_ND. The hatched line between amygdala and hippocampus reflects additional shared correlation. Circular hatched lines denote parameters estimated with error.</p

Latent variable model path analyses.

<p>Latent variable model path analyses.</p