1 - (SYM 53) Hormone-mood Synchrony: A Novel Methodology to Examine the Link Between Ovarian Steroid Changes and Mood Symptoms in Female Adolescents

Background. Starting at puberty, females face increased risk of developing mood disorders compared to males. Evidence supports differential mood sensitivity to ovarian steroid changes (i.e., estradiol (E2) and progesterone(P4)) as an etiological pathway explaining this divergence between sex. However, the field has yet to identify methodology to quantify individual differences in ovarian hormone sensitivity with respect to mood changes. The current study highlights the application of a novel method that calculates the synchrony (or coupling) between daily changes in ovarian steroids and mood symptoms.

Methods. 79 female adolescents aged 11-14 provided daily urine samples and mood ratings (11 selected mood symptoms) for one menstrual cycle (average gynecological age = 12.42). We applied a time-lagged cross correlation analysis to quantify the within-person degree of synchrony between person-standardized urinary metabolites of E2 and P4 and mood ratings. The mood time series was held steady; lags and leads of hormone levels across the collection period were created.

Results. 52% of participants had mood sensitivity to E2 (predominately sensitive to E2 decreases with a 3-day lag). 51% were mood-sensitive to P4 (sensitive to P4 change regardless of direction with a 2.5-day lag). 5 participants did not exhibit mood sensitivity to E2 or P4 for any symptom tested. Anger and irritability, depressed mood, and mood swings showed the strongest synchrony with both E2 and P4. For participants mood-sensitive to E2, the lag between hormone-change and mood change was greater for anger symptoms (4 days) compared to mood swings (2.6 days) (p=0.01). Anovulatory participants (n=21) had greater synchrony between P4 changes and anger (p=0.02) and mood swings (p=0.01). Further, 58% who were mood-sensitive to ovarian steroids had a biological parent with self-reported reproductive-related mood disturbances (e.g., postpartum depression).

Conclusion. Compared to extant methods, the present technique provides a more comprehensive examination of how ovarian steroid and mood symptom timeseries move together over time to determine hormone-lead mood-symptom-lag relationships. This allows researchers to better understand predictive validity of individual E2 and/or P4 sensitivity with respect to depression onset. Clinical applications will be discussed including early screening tool development, precise timing of interventions aligned with mood flux across the menstrual cycle, and personalized treatment based on individual hormone sensitivities.