Association between aromatase in human brains and personality traits

Abstract

Aromatase, an enzyme that converts androgens to estrogens, has been reported to be involved in several brain functions, including synaptic plasticity, neurogenesis, neuroprotection, and regulation of sexual and emotional behaviours in rodents, pathophysiology of Alzheimer’s disease and autism spectrum disorders in humans. Aromatase has been reported to be involved in aggressive behaviours in genetically modified mice and in personality traits by genotyping studies on humans. However, no study has investigated the relationship between aromatase in living brains and personality traits including aggression. We performed a positron emission tomography (PET) study in 21 healthy subjects using 11C-cetrozole, which has high selectivity and affinity for aromatase. Before performing PET scans, subjects answered the Buss-Perry Aggression Questionnaire and Temperament and Character Inventory to measure their aggression and personality traits, respectively. A strong accumulation of 11C-cetrozole was detected in the thalamus, hypothalamus, amygdala, and medulla. Females showed associations between aromatase levels in subcortical regions, such as the amygdala and supraoptic nucleus of the hypothalamus, and personality traits such as aggression, novelty seeking, and self-transcendence. In contrast, males exhibited associations between aromatase levels in the cortices and harm avoidance, persistence, and self-transcendence. The association of aromatase levels in the thalamus with cooperativeness was common to both sexes. The present study suggests that there might exist associations between aromatase in the brain and personality traits. Some of these associations may differ between sexes, while others are likely common to both.

Quantification of aromatase binding in the female human brain using [11C]cetrozole positron emission tomography

“…Fine mapping and quantification of regional brain expression of aromatase in vivo are important to better understand physiological and pathological conditions. To assess aromatase in vivo, positron emission tomography (PET) combined with carbon-11 labeled reversible aromatase inhibitors has been employed, using tracers like [ 11 C]vorozole (Biegon et al, 2010(Biegon et al, , 2015 and, more recently, [ 11 C]cetrozole (Takahashi et al, 2018). Further quantification of aromatase binding can be performed by applying suitable mathematical models on the data both on the regional level, in specific volumes of interests (VOIs), and on a voxel level, to produce parametric images.…”

“…Further quantification of aromatase binding can be performed by applying suitable mathematical models on the data both on the regional level, in specific volumes of interests (VOIs), and on a voxel level, to produce parametric images. In humans, the highest binding to aromatase has been found in the thalamus and hypothalamus, followed by the medulla, amygdala, nucleus accumbens, caudate nucleus, putamen, hippocampus, and cortex (Biegon, 2015;Biegon et al, 2010Biegon et al, , 2015Takahashi et al, 2018), thus in brain regions of relevance for reproductive as well as mental functions. On the other hand, the cerebellum has been selected as reference region because of low aromatase expression (Biegon, 2015;Biegon et al, 2010Biegon et al, , 2015Takahashi et al, 2018).…”

“…In humans, the highest binding to aromatase has been found in the thalamus and hypothalamus, followed by the medulla, amygdala, nucleus accumbens, caudate nucleus, putamen, hippocampus, and cortex (Biegon, 2015;Biegon et al, 2010Biegon et al, , 2015Takahashi et al, 2018), thus in brain regions of relevance for reproductive as well as mental functions. On the other hand, the cerebellum has been selected as reference region because of low aromatase expression (Biegon, 2015;Biegon et al, 2010Biegon et al, , 2015Takahashi et al, 2018). This is in line with postmortem analyses demonstrating mRNA levels being highest in the hypothalamus and thalamus, intermediate in the amygdala and hippocampus followed by the frontal cortex, and lowest in the cerebellum (Sasano, Takashashi, Satoh, Nagura, & Harada, 1998).…”

“…The novel aromatase radioligand [ 11 C]cetrozole has been shown to bind specifically to aromatase, with higher signal-to-noise ratio than [ 11 C]vorozole in nonhuman primates and without accumulation of radiolabeled metabolites in the brain of rats (Takahashi et al, 2014). In humans, [ 11 C]cetrozole binding in men was found to be higher in the left hypothalamus than in women (Takahashi et al, 2018); additionally, [ 11 C]cetrozole binding in the left amygdala correlated positively with aggressiveness in the women. In previous studies with [ 11 C]cetrozole, both in humans and nonhuman primates, aromatase was quantified using plasma-input function as well as reference region approaches (Takahashi et al, 2014(Takahashi et al, , 2018, but no extensive validation of tracer kinetic models or methods for generating parametric images has been performed for this tracer.…”

“…In humans, [ 11 C]cetrozole binding in men was found to be higher in the left hypothalamus than in women (Takahashi et al, 2018); additionally, [ 11 C]cetrozole binding in the left amygdala correlated positively with aggressiveness in the women. In previous studies with [ 11 C]cetrozole, both in humans and nonhuman primates, aromatase was quantified using plasma-input function as well as reference region approaches (Takahashi et al, 2014(Takahashi et al, , 2018, but no extensive validation of tracer kinetic models or methods for generating parametric images has been performed for this tracer. Thus, the aims of the present study were to (a) evaluate tracer kinetic models (Gunn, Gunn, & Cunningham, 2001) for quantitative analysis of [ 11 C] cetrozole in humans, based on plasma-and reference tissue input data, (b) to evaluate methods for producing parametric images of aromatase binding, and (c) to investigate the effect of scan duration on the above outcome parameters.…”