Exogenous testosterone enhances responsiveness to social threat in the neural circuitry of social aggression in humans

Background: In a range of species, the androgen steroid testosterone is known to potentiate neural circuits involved in intraspecific aggression. Disorders of impulsive aggression in humans have likewise been associated with high testosterone levels, but human evidence for the link between testosterone and aggression remains correlational and inconclusive. Methods: Twelve female participants underwent functional magnetic resonance imaging during three sessions while viewing stimuli differing in social threat value: angry and happy facial expressions. The first session served to establish associations between baseline hormone levels and neural activation. Participants were retested in a second and third session after placebo-controlled sublingual administration of.5 mg testosterone. Results: Findings demonstrate consistent activation to angry versus happy faces in areas known to be involved in vertebrate reactive aggression, such as the amygdala and hypothalamus. Suprathreshold clusters were also found in the orbitofrontal cortex (Brodmann area 47), a region implicated in impulse control in humans. Baseline endocrine profiles of high testosterone and low cortisol were associated with stronger activation in subcortical structures. Neural responses in most activated regions were more persistent after testosterone administration than after placebo. Conclusions: These data demonstrate that testosterone enhances responsiveness in neural circuits of social aggression. Based on animal literature, it is argued that actions of testosterone on subcortical reactive aggression circuits give rise to this effect. Implications for our understanding of the pathophysiology of disorders of impulsive aggression are discussed.