Aggression-related brain function assessed with the Point Subtraction Aggression Paradigm in fMRI.

The Point Subtraction Aggression Paradigm (PSAP) measures aggressive behavior in response to provocations. The aim of the study was to implement the PSAP in a functional neuroimaging environment (fMRI) and evaluate aggression-related brain reactivity including response to provocations and associations with aggression within the paradigm. Twenty healthy participants completed two 12-min PSAP sessions within the scanner. We evaluated brain responses to aggressive behavior (removing points from an opponent), provocations (point subtractions by the opponent), and winning points. Our results showed significant ventral and dorsal striatal reactivity when participants won a point and removed one from the opponent. Provocations significantly activated the amygdala, dorsal striatum, insula, and prefrontal areas. Task-related aggressive behavior was positively correlated with neural reactivity to provocations in the insula, the dorsal striatum, and prefrontal areas. Our findings suggest the PSAP within an fMRI environment may be a useful tool for probing aggression-related neural pathways. Activity in the amygdala, dorsal striatum, insula, and prefrontal areas during provocations is consistent with the involvement of these brain regions in emotional and impulsive behavior. Striatal reactivity may suggest an involvement of reward during winning and stealing points.

Testosterone levels in healthy men correlate negatively with serotonin 4 receptor binding.

The serotonergic system integrates sex steroid information and plays a central role in mood and stress regulation, cognition, appetite and sleep. This interplay may be critical for likelihood of developing depressive episodes, at least in a subgroup of sensitive individuals. The serotonin 4 receptor (5-HT4R) indexes central serotonergic tonus, which may be related to endogenous sex-steroid levels in the mentally healthy state even though this remains elusive. Here we evaluate if peripheral levels of estradiol and testosterone are associated with 5-HT4R binding as imaged by [11C]SB207145 positron emission tomography in a group of 41 healthy men. We estimated global 5-HT4R binding using a latent variable model framework, which models shared correlation between 5-HT4R across multiple brain regions (hippocampus, amygdala, posterior and anterior cingulate, thalamus, pallidostriatum and neocortex). We tested whether testosterone and estradiol predict global 5-HT4R, adjusting for age. We found that testosterone, but not estradiol, correlated negatively with global 5-HT4R levels (p=0.02) suggesting that men with high levels of testosterone have higher cerebral serotonergic tonus. Our findings corroborate the link between sex hormone levels and serotonin signalling. Future longitudinal studies in clinical relevant populations are needed to elucidate the potential importance of testosterone in the pathophysiology of e.g. major depression and its treatment.