Menstrual cycle effects on rule-plus-exception category learning vary by BDNF genotype

Poster Session C - Sunday, March 30, 2025, 5:00 – 7:00 pm EDT, Back Bay Ballroom/Republic Ballroom

Mateja Perovic¹ (m.perovic@mail.utoronto.ca), Janice Hou¹, Shreeansha Bhattarai¹, Cathlin Han¹, Michael Mack¹; ¹University of Toronto

Both brain-derived neurotrophic factor (BDNF) and ovarian hormones have established effects on neuroplasticity, learning and memory. Critically, ovarian hormones modulate BDNF expression across the menstrual cycle and its animal analogues. In order to examine the effects of this complex interaction on cognition, we use BDNF genetic polymorphism as an estimate of participants’ baseline BDNF availability and study their performance on a rule-plus-exception category learning task at two points in the menstrual cycle. We find that, while Met homozygotes show advantages during the early follicular phase (typically characterized by low levels of ovarian hormones), Val homozygotes outperform them in the late follicular phase (typically characterized by high estradiol), indicating nuanced, genotype- and menstrual cycle-specific effects on category learning ability. Follow-up analyses suggest that the effect may be driven by Met carriers’ increased sensitivity to estradiol: both overall levels of estradiol and rate of change in estradiol between menstrual cycle phases are negatively associated with performance in Met carriers but not Val homozygotes. These results provide the first evidence of BDNF genotype interacting with the menstrual cycle to predict cognitive performance in women and deepen our understanding of menstrual cycle-dependent changes in memory and learning. Notably, both BDNF and ovarian hormones have major effects on the hippocampus, and the category learning task we use, which necessitates memory integration and differentiation, is significantly associated with hippocampal processes. As such our findings are of interest to neuroscientists broadly interested in hippocampus and its role in learning.

Topic Area: LONG-TERM MEMORY: Episodic