Brain activation during emotion regulation in women with premenstrual dysphoric disorder

Abstract

Background: Difficulties in regulating emotions are linked to the core symptoms of premenstrual dysphoric disorder (PMDD). We therefore investigated the neural substrates of emotion-regulation problems in women with PMDD.

Methods: On the basis of self-evaluations over 2 months on the Daily Record of Severity of Problems, eligible participants were assigned to two groups: PMDD and control (18 per group). Functional magnetic resonance imaging (fMRI) and a well-validated task were used to assess brain function during emotion regulation. Participants were tested twice, once during the follicular (asymptomatic) and once in the late luteal (symptomatic) phase of the menstrual cycle.

Results: Women with PMDD gave higher ratings of negative affect in the luteal phase than in the follicular phase, and compared with healthy control participants during the luteal phase. A region-of-interest fMRI analysis indicated that during the late luteal phase, women with PMDD had hypoactivation in right dorsolateral prefrontal cortex (dlPFC) during all conditions of the emotion-regulation task, not only in the contrast that isolated emotion regulation. An exploratory whole-brain, voxel-wise analysis showed that women with PMDD had less activation in the precentral gyrus during the luteal phase than the follicular phase, and less activation in the postcentral gyrus compared with control participants.

Conclusions: During the luteal phase of the menstrual cycle, women with PMDD experience difficulty regulating emotions. Hypoactivation in the right dlPFC may contribute to this problem, but may be related more generally to other affective symptoms of PMDD. Hypofunction in the right pre- and postcentral gyri warrants additional study.

Keywords: Premenstrual dysphoric disorder; PMDD; emotion regulation; fMRI; menstrual cycle; neuroendocrinology.

Fig. 1.

Schematic of event sequence during trials of the emotion regulation task. Participants viewed the instruction ‘close’ or ‘far’ (2 s), followed by a negative or neutral image (8 s), and then rated their degree of negative affect (⩽3 s). An inter-stimulus interval of ~3 s preceded the next trial (see Methods section).

Fig. 2.

Negative emotion after each trial condition during the emotion regulation task. Women with PMDD gave reports of stronger negative emotion in the luteal phase than in the follicular phase, and compared with healthy controls during the luteal phase. No group or phase differences were detected in the other task conditions, n = 18/group. *p <0.05. Error bars indicate ± 1 s.e.m.

Fig. 3.

Right dlPFC activation for each group and each task condition during the emotion regulation task. Parameter estimates of right dlPFC activation during each task condition were not significantly different between groups or phases. N = 18/group. Error bars indicate ± 1 s.e.m.

Fig. 4.

Women with PMDD had significantly less activation in the right dlPFC while performing the emotion regulation task during the late luteal phase, when they are symptomatic. Statistical parameter estimates of right dlPFC activity during all trials of the emotion regulation task combined (compared with the intertrial-baseline condition) were significantly lower for women with PMDD during the luteal phase than during the follicular phase, and compared with healthy women during the luteal phase. N = 18/group. *p <0.05. Error bars indicate ± 1 s.e.m.

Fig. 5.

Whole-brain voxel-wise analysis results. Top: Group comparison of regulation-related activity (far, negative greater than close, negative) in the luteal phase v. the follicular phase, showing significantly greater activation in the right precentral gyrus during the follicular phase in PMDD women, N = 18/group, FWE cluster corrected, Z > 2.3, p < 0.05, centered on peak voxel at 58, −4, 34. Bottom: A similar analysis showed significantly greater regulation-related activity in the right postcentral gyrus of healthy controls compared with women with PMDD, both tested in the luteal phase, FWE cluster-corrected, Z > 2.3, p < 0.05, centered on peak voxel at 42, −28, 58.