The impact of motherhood on anxiety symptoms over the menstrual cycle: A translational approach in female rats and women

Fluctuating sex hormones across the estrous/menstrual cycle in female rats and women are associated with changes in anxiety, which could contribute to the maintenance of anxiety disorders. Pregnancy causes long-term changes in sex hormonal fluctuations, yet extant research has focused on reproductively inexperienced females. This study employed a cross-species approach to assess whether the impact of estrous/menstrual cycle on anxiety differs pre- versus post-motherhood. Naturally cycling virgin rats (n=14) and mother rats (n=18) were tested twice on the open field maze, light-dark box, and elevated plus maze to measure anxiety-like behaviour; during metestrus (low sex hormones) and proestrus (high sex hormones). In addition, a human community sample of naturally cycling non-mothers (n=35) and mothers (n=28) completed the Patient Health Questionnaire-4 at three timepoints; during the early-follicular phase (low sex hormones), ovulation (high sex hormones), and mid-luteal phase (high sex hormones). Replicating past research, virgin rats showed higher anxiety-like behaviour during metestrus versus proestrus. In contrast, mother rats showed similar anxiety-like behaviour irrespective of estrous phase. Replicating past research in humans, non-mothers reported higher anxiety and depression during the early-follicular phase compared to other menstrual phases. In contrast, mothers reported similar anxiety and depression irrespective of menstrual phase. Changes in anxiety coincident with cycling hormones is an evolutionary conserved feature of the estrous/menstrual cycle in rats and women, which may be mitigated post-motherhood in both species. These findings highlight the importance of considering reproductive status in studies on anxiety in females.