The influence of androstadienone during psychosocial stress is modulated by gender, trait anxiety and subjective stress: An fMRI study

Androstadienone (ANDR), a bodily secreted steroid compound, is a socially relevant chemosignal that modulates subjective and (neuro)physiological responses, predominantly in females. The impact of ANDR on stress responses in males and females has not been explored. Therefore, this fMRI study aimed to examine psychosocial stress reactions induced by mental arithmetic and social evaluation on behavioral and hormonal levels (46 participants: 15 naturally cycling females in their early follicular phase (EF), 15 females on hormonal contraceptives (HC) and 16 males); and on a neural level (40 participants: 13 EF-females, 13 HC-females and 14 males) in an ANDR and placebo treatment repeated-measures design. While no gender differences emerged in subjective ratings and performance during stress, neural activation patterns differed significantly. Besides, ANDR attenuated the post-stress increase of negative mood in all participants. Region of interest analyses showed that irrespective of treatment, males showed stronger activation of the dorsolateral prefrontal cortex (DLPFC) than females. At the whole brain level, gender differences emerged indicating stronger fronto-parietal activation in males compared to HC-females on both treatments. Males showed stronger visual and fusiform activation than EF-females under ANDR. Both female groups did not show stronger activation than males. Further, error ratio in the ANDR-stress condition was positively associated with their post-stress cortisol level and increase in subjective stress in males; and male DLPFC activity in the ANDR-stress condition was negatively associated with trait anxiety. Surprisingly, compared to HC-females, EF-female only showed stronger activation of arousal-related areas under placebo treatment. Taken together, these findings suggest that the male stress reaction under social evaluative threat was stronger than female stress reactions as a function of ANDR. More specifically, this effect on behavioral and neural stress reactions seems to depend on trait anxiety in males only. The study highlights the significance of a chemosignal in enhancing social threat that may facilitate adaptive stress responses