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Perimenstrual Hormone Withdrawal, Executive Functioning, and Proximal Suicide Risk: An Experimental Approach

Subject Area Personality Psychology, Clinical and Medical Psychology, Methodology
Biological Psychology and Cognitive Neuroscience
Term from 2021 to 2024
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 470147139
 
Final Report Year 2024

Final Report Abstract

Throughout the reproductive lifespan of individuals with menstrual cycles, suicide is one of the leading causes of death worldwide. However, despite decades of research, suicide prevention has not significantly improved. There is an urgent need to understand factors that increase the short-term risk of suicidality. This project is part of the first experimental studies to investigate whether the menstrual cycle might be such a factor. In a first step, we found that transdiagnostic outpatients with suicidal ideation (SI) exhibit significant worsening of their SI/affective symptoms during the perimenstrual phase when estrogen (E2) and progesterone (P4) are falling. Our two randomized controlled trials (RCTs) show that administering exogenous E2 and P4 or E2 alone can prevent this worsening. That is, by buffering the perimenstrual E2 and P4 withdrawal, perimenstrual worsening of SI and affective symptoms can be prevented. This provides the first evidence of a causal link between the cycle and suicidality. We conclude that outpatients with SI are at high risk for affective sensitivity to cycle-related hormone changes (i.e., affective hormone sensitivity). In the next step, I studied whether patients with SI additionally suffer from cognitive hormone sensitivity and found that their executive functions (essential for problem-solving and future-oriented behavior) decline perimenstrually. However, administering E2 prevents this decline. This is the first experimental evidence of menstrual cycle effects on cognition in patients with SI, revealing a high risk for cognitive hormone sensitivity in this population. Next to showing high hormone sensitivity in patients with SI, the third part of this project investigated a potential biomarker of this sensitivity, vagally-mediated heart rate variability (HRV). We were the first to investigate the link between HRV cyclicity and affect cyclicity. In a non-clinical sample, I found that only individuals with atypical HRV changes experience increased negative affect perimenstrually. I collected nightly HRV data during one of our RCTs, and I am currently analyzing this data to examine HRV cyclicity in patients with SI. In sum, this project has significantly contributed to our understanding of menstrual cycle effects on suicidality: Patients with SI are at high risk for perimenstrual worsening of SI, affective symptoms, and cognitive functioning caused by the perimenstrual withdrawal of ovarian hormones (particularly E2). In addition, the project has identified atypical HRV cyclicity as a potential biomarker of this hormone sensitivity. Future studies will delve deeper into these mechanisms using the data collected during the project to improve our understanding of how and for whom the menstrual cycle may heighten the risk of imminent suicidality.

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