Testosterone administration in women increases amygdala responses to fearful and happy faces

Data from both rodents and humans show that testosterone reduces fear. This effect is hypothesized to result from testosterone's down regulating effects on the amygdala, a key region in the detection of threat and instigator of fight-or-flight behavior. However, neuroimaging studies employing testosterone administration in humans have consistently shown increased amygdala responsivity. Yet, no study to date has investigated specifically how testosterone affects the amygdala response to fearful emotional expressions. Such stimuli signal the presence of environmental threat and elicit robust amygdala responses that have consistently been associated with anxious traits. In the present study, we therefore used functional magnetic resonance imaging combined with a single administration of 0.5mg testosterone in 12 healthy women to assess testosterone's effects on amygdala responses to dynamic fearful (and happy control) faces. Our results show that both stimuli activate the amygdala. Notably, testosterone increased the amygdala response to both stimuli, and to an equal degree. Thus, testosterone appears not to reduce fear by attenuating the amygdala response toward signals of threat. Data further show that testosterone selectively increases activation of the superficial amygdala (SFA) and, to a lesser extent, the basolateral amygdala (BLA). No effect was found in the central nucleus, which is involved in the generation of autonomic fear responses. Both the SFA and BLA are considered input regions, and enhanced activation by testosterone might reflect the role of this hormone in adaptive responding to socially relevant stimuli. Furthermore, literature on the distinct roles of the SFA and BLA in fear processing show that increased activation of these subregions of the amygdala is consistent with a fear reducing effect of testosterone.