Men with high serotonin 1B receptor binding respond to provocations with heightened amygdala reactivity

Serotonin signalling influences amygdala reactivity to threat-related emotional facial expressions in healthy adults, but in vivo serotonin signalling has never been investigated in the context of provocative stimuli in aggressive individuals. The aim of this study was to evaluate associations between serotonin 1B receptor (5-HT_1BR) levels and brain reactivity to provocations. We quantified regional 5-HT_1BR binding using [¹¹C]AZ10419369 positron emission tomography (PET) and measured brain activation following provocations with functional magnetic resonance imaging (fMRI) in eighteen violent offenders and 25 healthy control subjects. The point-subtraction aggression paradigm (PSAP) was used in fMRI to elicit provocations in terms of monetary subtractions from a fictive opponent. We estimated global 5-HT_1BR binding using a linear structural equation model, with a single latent response variable (LV_1B) modelling shared correlation between 5-HT_1BR binding across multiple brain regions (neocortex, anterior and posterior cingulate cortex, raphe, amygdala, hippocampus and striatum). We tested whether the LV_1B was associated with amygdala, striatal and prefrontal reactivity to provocations, adjusting for age, injected mass and group. Across participants, LV_1B was statistically significantly positively associated with amygdala (p = 0.01) but not with striatal (p = 0.2) or prefrontal reactivity to provocations (p = 0.3). These findings provide novel evidence that 5-HT_1BR levels are linked to amygdala reactivity to provocations in a cohort of men displaying a wide range of aggressive behavior. The data suggest that 5-HT_1BR represents an intriguing target for reducing excessive neural reactivity to provocations and thereby putatively violent behavior.