Premenstrual dysphoric disorder and prefrontal reactivity during anticipation of emotional stimuli

Eur Neuropsychopharmacol. 2013 Nov;23(11):1474-83. doi: 10.1016/j.euroneuro.2013.08.002. Epub 2013 Aug 17.


Premenstrual disorder (PMDD) affects around 5% of women in childbearing ages. An increased sensitivity in emotion processing areas of the brain to variations in ovarian steroid levels has been suggested as part of the pathophysiology in PMDD, but prior neuroimaging studies of emotion processing are yet inconclusive. Previous behavioral studies of women with PMDD have, however, reported enhanced luteal phase startle responsivity during emotional anticipation. Here we used functional magnetic resonance imaging (fMRI) to investigate central neural circuitry activity during anticipation of, and exposure to, emotional stimuli across the menstrual cycle in women with and without PMDD. As compared to healthy controls, women with PMDD displayed significantly enhanced reactivity in the prefrontal cortex during anticipation of, but not exposure to, negative emotional stimuli during the luteal phase. In PMDD patients, BOLD reactivity during anticipation or viewing of negative emotional stimuli was not dependent on absolute levels of estradiol or progesterone. However, progesterone levels were positively correlated with emotion-induced reactivity in the dorsolateral prefrontal cortex to positive emotional stimuli. These findings suggest that cortical emotional circuitry reactivity during anticipation is altered in PMDD during the luteal phase, which might be part of the pathophysiology behind the emotional symptoms or lack of emotional control reported by women with PMDD.

Keywords: ACC; Anticipation; BA; BOLD; Brodmann area; CD-scale; DICOM; DSM; Emotion; Estrogen; HC; IAPS; IFG; M.I.N.I.; MNI; MR; NIfTI; OFC; PMDD; Premenstrual dysphoric disorder; Progesterone; ROI; SPM; T; TE; TR; anterior cingulate cortex; blood oxygenation level dependent; cluster size; cyclicty diagnoser scale; diagnostic and statistical module of mental disorders; digital imaging and communications in medicine; dlPFC; dorsolateral prefrontal cortex; echo time; fMRI; functional magnetic resonance imaging; healthy control; inferior frontal gyrus; international affective pictures system; k; magnetic resonance imaging; mini international neuropsychiatric interview; montreal neurological institute; neuroimaging informatics technology initiative; orbitofrontal cortex; premenstrual dysphoric disorder; regions of interest; statistical parametric mapping; tesla; time of repetition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anticipation, Psychological / physiology*
  • Case-Control Studies
  • Emotions / physiology*
  • Estradiol / blood
  • Female
  • Functional Neuroimaging
  • Humans
  • Menstrual Cycle / physiology
  • Photic Stimulation
  • Prefrontal Cortex / physiology*
  • Premenstrual Syndrome / blood
  • Premenstrual Syndrome / physiopathology*
  • Progesterone / blood


  • Progesterone
  • Estradiol