Recent calls from the President, Surgeon General, and the NIMH-sponsored Suicide Research Prioritization Agenda emphasize a dire need for the identification of biological predictors of acute suicide risk that are amenable to intervention. In response, the proposed experimental work investigates a causal role of perimenstrual (around menses) withdrawal from the hormones estradiol (E2) and progesterone (P4) in previously-documented acute perimenstrual increases in suicidality. The proposed project also fully prepares the candidate for a uniquely impactful research career in the pathophysiology of suicide.
The aim of the proposed K99 research is to test the hypothesis that natural perimenstrual E2/P4 withdrawal acutely increases suicidality. Using a placebo-controlled, within-person design in a sample of 30 women with current suicidal ideation but minimal risk for suicide attempt, the experiment will test the hypothesis that suicidality will be heightened during natural perimenstrual E2/P4 withdrawal (under placebo), but that experimental prevention of this perimenstrual E2/P4 withdrawal will prevent these perimenstrual increases in suicidality.
The aim of the R00 research will be to disentangle the roles of E2 and P4 withdrawal in perimenstrual worsening of suicidality using an expanded three-arm within-person experiment (perimenstrual E2/P4 withdrawal under placebo, E2 stabilization [with perimenstrual P4 withdrawal], and P4 stabilization [with perimenstrual E2 withdrawal]), also in 30 women with current suicidal ideation but minimal suicide attempt risk. It is predicted that only natural P4 withdrawal conditions will be associated with worsened suicidality, mediated by withdrawal from P4-derived neurosteroids. Both projects will utilize multi-modal measurement (tasks, interviews, phone assessments, and ecological momentary assessment [EMA]). Mentorship: Experts from UNC Chapel Hill and neighboring Duke University will mentor the candidate: Susan Girdler, Ph.D. (mentor) will provide mentorship in hormone manipulation. Mitch Prinstein, Ph.D. (co-mentor) will provide mentorship in suicide and risk management. David Rubinow, M.D. contributes expertise in the neurobiological effects of ovarian hormones. Steven Young, M.D., Ph.D. contributes expertise in manipulation of the menstrual cycle. Daniel Bauer, Ph.D. provides expertise in advanced statistics. M. Zachary Rosenthal, Ph.D. contributes expertise in suicidality and EMA. Career Goal: The candidate is committed to a research career focused on the role of hormone changes in impulsivity and suicidality. Her goal is to contribute knowledge through R01-funded projects while also translating findings into treatments. Career Development: Her previous work has established prospective associations between acute hormone changes and impulsivity (aggression, alcohol abuse); this award will allow her to develop skills to conduct safe experiments that will determine the causal role of hormone change in suicidality. Training Outcomes include skills in hormonal experiments, research-based suicide risk management, ecological momentary assessment, and multimodal measurement of suicide-related constructs.

Public Health Relevance

Menstrual cycle-linked hormone withdrawal is correlated with suicide attempts; the proposed line of research will provide the first experimental evidence regarding the effects of menstrual cycle-linked ovarian hormone withdrawal on perimenstrual (around menses) increases in suicidality. By providing an additional period of mentored research training in the experimental manipulation of ovarian hormones and other key methods, the present proposal builds on the candidate?s previous longitudinal research on the role of ovarian steroid changes in emotional and behavioral symptoms of psychopathology. The methodological skills training and pilot data acquired during the proposed project will leave the candidate poised to compete for larger scale research focused on the combined use of biological and behavioral interventions for chronically suicidal women.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Career Transition Award (K99)
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Special Emphasis Panel (ZMH1-ERB-M (05))
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Mclinden, Kristina
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University of North Carolina Chapel Hill
Schools of Medicine
Chapel Hill
United States
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Eisenlohr-Moul, Tory A; Miller, Adam B; Giletta, Matteo et al. (2018) HPA axis response and psychosocial stress as interactive predictors of suicidal ideation and behavior in adolescent females: a multilevel diathesis-stress framework. Neuropsychopharmacology 43:2564-2571
Dawson, Danyelle N; Eisenlohr-Moul, Tory A; Paulson, Julia L et al. (2018) Emotion-related impulsivity and rumination predict the perimenstrual severity and trajectory of symptoms in women with a menstrually related mood disorder. J Clin Psychol 74:579-593
Walsh, Erin C; Eisenlohr-Moul, Tory A; Pedersen, Cort A et al. (2018) Early Life Abuse Moderates the Effects of Intranasal Oxytocin on Symptoms of Premenstrual Dysphoric Disorder: Preliminary Evidence From a Placebo-Controlled Trial. Front Psychiatry 9:547
Roberts, Bethan; Eisenlohr-Moul, Tory; Martel, Michelle M (2018) Reproductive steroids and ADHD symptoms across the menstrual cycle. Psychoneuroendocrinology 88:105-114
Peters, Jessica R; Eisenlohr-Moul, Tory A; Walsh, Erin C et al. (2018) Exploring the pathophysiology of emotion-based impulsivity: The roles of the sympathetic nervous system and hostile reactivity. Psychiatry Res 267:368-375
Miller, Adam Bryant; Eisenlohr-Moul, Tory; Giletta, Matteo et al. (2017) A within-person approach to risk for suicidal ideation and suicidal behavior: Examining the roles of depression, stress, and abuse exposure. J Consult Clin Psychol 85:712-722
Schmalenberger, K M; Eisenlohr-Moul, T A; Surana, P et al. (2017) Predictors of premenstrual impairment among women undergoing prospective assessment for premenstrual dysphoric disorder: a cycle-level analysis. Psychol Med 47:1585-1596
Walsh, Erin; Carl, Hannah; Eisenlohr-Moul, Tory et al. (2017) Attenuation of Frontostriatal Connectivity During Reward Processing Predicts Response to Psychotherapy in Major Depressive Disorder. Neuropsychopharmacology 42:831-843
Flynn, Sarah McQueary; Eisenlohr-Moul, Tory A; Segerstrom, Suzanne C et al. (2017) High trait shame undermines the protective effects of prevalence knowledge on state shame following HPV/CIN diagnosis in women. J Behav Med 40:814-820
Martel, Michelle M; Eisenlohr-Moul, Tory; Roberts, Bethan (2017) Interactive effects of ovarian steroid hormones on alcohol use and binge drinking across the menstrual cycle. J Abnorm Psychol 126:1104-1113

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