Women and men are known to have different vulnerabilities to psychiatric and other illnesses. There are a variety of reasons, including biological differences between the sexes and a vast number of socio-demographic and cultural factors.

Thanks in significant part to research by BBRF Scientific Council member, three-time BBRF Distinguished Investigator and Selo Prize winner Myrna M. Weissman, Ph.D., it has been known for several decades that women have a much greater lifetime risk than men of developing depression—as much as a 70 percent greater risk.

One remarkable and related fact that is rarely discussed is that women are three times more likely than men to report suicidal ideation, suicidal planning, or a suicide attempt over the lifespan.

Both of these disparities in risk have some relation to cyclical ovarian hormone fluctuations; the details in each case have been the subject of intense research over many years. Recently, a team of investigators led by 2018 BBRF Young Investigator Tory Anne Eisenlohr-Moul, Ph.D., of the University of Illinois Chicago, published findings of what may be the most detailed study to date seeking to understand how daily changes in a range of psychiatric symptoms influence acute changes in suicidal ideation and planning, and how brain-based sensitivities to normal cycling hormones can shape these changes. Dr. Jacyln Ross and Jordan Barone were co-first authors of the team’s paper, which appeared in the American Journal of Psychiatry.

Given the greater female vulnerability to suicidal behavior, the team notes, “understanding suicide risk factors that are unique to females is critical to addressing the public health crisis” that suicide represents. There were nearly 50,000 deaths by suicide reported in the U.S. in the most recent year for which statistics are available.

A litany of psychiatric symptoms, noted at single time points, have been strongly correlated with suicide risk. These symptoms include depression, hopelessness, and anhedonia (the inability to experience pleasure), as well as the perception of being a burden to others, heightened sensitivity to rejection, agitation, anxiety, and anger. Although research identifying these correlates has begun to clarify who is most vulnerable to suicidal ideation and suicide attempts across the lifespan, “questions of when and how suicide risk increases remain largely unanswered,” the team notes in its paper. A knowledge gap of particular importance concerns short-term risk factors that can help clinicians predict when their patients may transition from thinking about suicide to making an actual plan for suicide, the team stresses. This helped to guide the design of their study.

Risk factors that vary over time, “beyond the usual suspects of psychopathology and sociodemographic variables,” were their focus, and specifically, the monthly menstrual cycle. “Accumulating evidence shows that ovarian hormone fluctuations modulate imminent suicide risk for many females, resulting in increased likelihood of suicide attempts and deaths during the premenstrual and menstrual weeks.” But studies to date have tended to involve small numbers of patients, have not distinguished chronic suicidal ideation from acute suicidal planning, and haven’t taken into account that people differ widely in their response to the monthly cycle. Patients with the cycle-linked mood disorder premenstrual dysphoric disorder (PMDD), who often report symptoms such as irritability and rage, have been found to have very high rates of suicidal behavior: according to another paper published by the team, about 72% of women with PMDD report suicidal thinking and about one-third report a history of suicide attempt.

The team recruited 119 psychiatric outpatients who experienced regular periods and reported past-month suicidal ideation. These participants provided a series of daily ratings of psychiatric symptoms across at least one menstrual cycle.

Nearly all of the psychiatric symptoms varied in correspondence with fluctuations (up or down) in daily suicidal ideation. A limited set of symptoms—depression, hopelessness, rejection sensitivity, and the perception of being a burden—were found to specifically predict an individual’s increases in suicidal planning. Of note, individuals also differed from one another with respect to which psychiatric symptoms were the best predictors of daily suicide risk, indicating a need for personalized approaches in the future, the team said.

It was observed that many patients demonstrated worsening of psychiatric symptoms, suicidal ideation, and suicidal planning over the “perimenstrual” period, i.e., around the time leading up to and during menstruation. Depressive symptoms (depression, hopelessness, perception of being a burden, and anhedonia) “were the most robust statistical factors predicting perimenstrual exacerbation of suicidality,” the team reported.

“While most past suicide research has highlighted broad psychopathological and sociodemographic factors as predictors of suicide risk, our study reveals an acute perimenstrual risk period for suicidal ideation and planning,” the team wrote. This, they said, “presents an opportunity for biological and psychosocial intervention” among those particularly at risk. By measuring fluctuations in suicidality over time, the research may help caregivers formulate predictions about when specific individuals are most at risk.

“We urge researchers to model individual symptom trajectories,” the team wrote, to better identify subtypes of neurobehavioral hormone sensitivity. The study’s finding that depressive symptoms are robust predictors of perimenstrual worsening of suicidal ideation and planning suggests to the team that “intervention efforts may benefit from strategies that specifically target depressive symptoms as they fluctuate across the cycle, given their powerful role in the cycle-suicidality relationship.”