Menstrual cycle-related changes in amygdala morphology are associated with changes in stress sensitivity

Abstract

Premenstrual increases in negative mood are thought to arise from changes in gonadal hormone levels, presumably by influencing mood regulation and stress sensitivity. The amygdala plays a major role in this context, and animal studies suggest that gonadal hormones influence its morphology. Here, we investigated whether amygdala morphology changes over the menstrual cycle and whether this change explains differences in stress sensitivity. Twenty-eight young healthy women were investigated once during the premenstrual phase and once during the late follicular phase. T1-weighted anatomical images of the brain were acquired using magnetic resonance imaging and analyzed with optimized voxel-based morphometry. To measure mood regulation and stress sensitivity, negative affect was assessed after viewing strongly aversive as well as neutral movie clips. Our results show increased gray matter volume in the dorsal part of the left amygdala during the premenstrual phase when compared with the late follicular phase. This volume increase was positively correlated with the premenstrual increase in stress-induced negative affect. This is the first study showing structural plasticity of the amygdala in humans at the macroscopic level that is associated with both endogenous gonadal hormone fluctuations and stress sensitivity. These results correspond with animal findings of gonadal hormone-mediated neural plasticity in the amygdala and have implications for understanding the pathogenesis of specific mood disorders associated with hormonal fluctuations.

Copyright © 2011 Wiley Periodicals, Inc.

Figures

Figure 1

Coronal view showing the significant increase in dorsal amygdala gray matter volume in the premenstrual versus late follicular phase (P < 0.001 uncorrected for visualization purposes; MNI‐coordinates: −15, −3, −9; R = right). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

Figure 2

Rank correlation between gray matter increase in the amygdala across the menstrual cycle and stress‐induced negative affect scores. X‐axis: Δ amygdala gray matter increase extracted from the peak voxel at −15, −3, −9 (premenstrual > late follicular). Y‐axis: Δ stress‐induced increase in negative affect across the menstrual cycle (premenstrual [stress − neutral] > late follicular [stress – neutral]).