Adolescent Girls’ Risk for Suicide Across the Menstrual Cycle: Examining Stress and Negative Valence Systems Longitudinally

Project Summary/Abstract
Suicide is the second leading cause of death (behind accidents) among those ages 10-34 years in the US and
is the cause of mortality most strongly linked to mental illness. Starting at approximately age 12 years, the rate
of suicidal thoughts and behaviors (STBs) increases dramatically, especially among girls, who experience STBs
at twice the rate for boys. These pronounced increases for adolescents and for girls have been well-documented
for decades and are seen in virtually every country/culture around the world, yet, there is no firm understanding
of why they exist. Moreover, very little is known about when risk is highest. The proposed research extends our
team’s prior work, funded by two prior R01 awards, examining adolescent girls’ stress responses as prospective
predictors of STB trajectories, and a K99/R00 award revealing that changes in reproductive hormones across
the menstrual cycle produce specific periods of high STB risk (particularly during the peri-menstrual phase)
among adult women. Specifically, we hypothesize that girls will report higher occurrence and severity of STBs
on days in the peri-menstrual phase than on days in other cycle phases (mid-follicular, ovulatory, mid-luteal),
that these increases will be mediated by daily changes in negative affect and stress-reactivity during the peri-
menstrual phase, and that girls with greater cyclical hormone sensitivity are at greater long-term risk of STBs,
particularly during times when interpersonal stress is elevated. We propose to test these hypotheses in a sample
of 200 clinically-referred girls ages 12-17 years who are at least one year post-menarche. The design begins
with 70 days (two cycles) of daily surveys to assess negative affect and STBs. In addition, girls will complete two
counterbalanced laboratory visits (at high risk peri-menstrual and low risk mid-follicular phases) during which we
will evaluate their affective and physiological (autonomic, cortisol, genomic) responses to a standardized
laboratory stressor. Next, girls will complete weekly surveys measuring cycle phase, interpersonal stress,
negative affect, and STBs through one year of follow up. The intensive two-month baseline phase allows us to
examine how the menstrual cycle shapes daily affective and physiological risk for STBs and lets us diagnose
each girl’s degree of hormone sensitivity. These baseline individual differences in hormone sensitivity then can
be examined as a predictor of STBs across the follow-up year of assessments, particularly during periods of
elevated social stress. This powerful design will clarify whether cyclical changes in daily STBs (Aim 1) are
mediated by affective and physiological STB risk factors, such as negative affect (Aim 2a; measured via daily
surveys) and social stress reactivity (Aim 2b; measured via lab-based behavioral, physiological, and molecular
biomarker assays), while also acknowledging critical moderation by both individual differences in hormone
sensitivity (i.e., not all girls will have severe cyclical mood changes) and time-varying interpersonal stress (Aim
3). This innovative study will address several long-standing questions in the literature, including why girls are at
increased risk, when girls may be most at risk, and which girls are at highest risk for future STBs.

Grant Number: 5R01MH122446-05
NIH Institute/Center: NIH
Principal Investigator: Elizabeth Andersen