Background: Premenstrual dysphoric disorder (PMDD), characterized by luteal phase-induced negative affect and loss of impulse control, often results in compromised social interactions. Although amygdala activation is generally linked to negative affect, increased amygdala reactivity to aversive stimuli in the luteal phase has not been consistently reported in PMDD. We tested the hypothesis that amygdala hyper-reactivity in PMDD is symptom specific, rather than generalized, and linked to socially relevant stimuli. Blood oxygenation level dependent signal changes during exposure to negative images with social and non-social content were evaluated in the mid-follicular and late luteal phase of the menstrual cycle. Fourteen women with PMDD and 13 healthy controls participated.
Results: When compared with healthy controls, women with PMDD in the luteal phase had enhanced reactivity to social stimuli compared to non-social stimuli in the amygdala and insula, but attenuated reactivity in the anterior cingulate cortex. Functional couplings between emotion processing and controlling areas were significantly different, being positive in women with PMDD and negative in healthy controls. Changes in progesterone levels in women with PMDD correlated positively with altered amygdala reactivity.
Conclusions: Socially relevant aversive stimulation elicited enhanced activity in affective processing brain regions that were functionally coupled to compromised activity in cognitive control areas. Because increased reactivity correlated positively with alterations in ovarian steroid levels, data preliminary support the hypothesis that enhanced progesterone sensitivity in PMDD affects corticolimbic processing of social emotions.