Lindsey Ossewaarde

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. Hum Brain Mapp, 2013.

The premenstrual phase of the menstrual cycle is associated with marked changes in normal and abnormal motivated behaviors. Animal studies suggest that such effects may result from actions of gonadal hormones on the mesolimbic dopamine (DA) system. We therefore investigated premenstrual changes in reward-related neural activity in terminal regions of the DA system in humans. Twenty-eight healthy young women underwent functional magnetic resonance imaging on 2 days during the menstrual cycle, once during the late follicular phase and once during the premenstrual phase, in counterbalanced order. Using a modified version of the monetary incentive delay task, we assessed responsiveness of the ventral striatum to reward anticipation. Our results show enhanced ventral striatal responses during the premenstrual as compared to the follicular phase. Moreover, this effect was most pronounced in women reporting more premenstrual symptoms. These findings provide support for the notion that changes in functioning of mesolimbic incentive processing circuits may underlie premenstrual changes in motivated behaviors. Notably, increases in reward-cue responsiveness have previously been associated with DA withdrawal states. Our findings therefore suggest that the sharp decline of gonadal hormone levels in the premenstrual phase may trigger a similar withdrawal-like state.