Association between neuroticism and amygdala responsivity emerges under stressful conditions

- We studied the effects of stress and neuroticism on amygdala responsivity.
- Fearful and happy facial stimuli were presented.
- We included a large cohort of young, healthy males (n = 120).
- Neuroticism only enhanced amygdala responses to fearful faces under stress.
- This constitutes a possible mechanism in the pathophysiology of affective disorders.

Increased amygdala reactivity in response to salient stimuli is seen in patients with affective disorders, in healthy subjects at risk for these disorders, and in stressed individuals, making it a prime target for mechanistic studies into the pathophysiology of affective disorders. However, whereas individual differences in neuroticism are thought to modulate the effect of stress on mental health, the mechanistic link between stress, neuroticism and amygdala responsivity is unknown.Thus, we studied the relationship between experimentally induced stress, individual differences in neuroticism, and amygdala responsivity. To this end, fearful and happy faces were presented to a large cohort of young, healthy males (n = 120) in two separate functional MRI sessions (stress versus control) in a randomized, controlled cross-over design.We revealed that amygdala reactivity was modulated by an interaction between the factors of stress, neuroticism, and the emotional valence of the facial stimuli. Follow-up analysis showed that neuroticism selectively enhanced amygdala responses to fearful faces in the stress condition.Thus, we show that stress unmasks an association between neuroticism and amygdala responsivity to potentially threatening stimuli. This effect constitutes a possible mechanistic link within the complex pathophysiology of affective disorders, and our novel approach appears suitable for further studies targeting the underlying mechanisms.