The CLEAR Lab, led by Tory Eisenlohr-Moul, Ph.D., seeks to CLarify the Endocrinology of Acute Risk for emotional distress, interpersonal problems, substance abuse, and suicide attempts across the menstrual cycle in at-risk females. We seek to clarify the underlying pathophysiology of DSM-5 premenstrual dysphoric disorder, cyclical worsening of other psychiatric disorders, and perimenopausal mood symptoms. We use both mechanistic experimental trials and intensive observational studies in clinical samples, with the ultimate goal of predicting and preventing severe psychiatric outcomes.
Currently, there are two questions that drive the majority of work in the CLEAR Lab:
QUESTION 1 – WHAT IS THE ROLE OF OVARIAN STEROID CHANGES IN ACUTE SUICIDALITY?:
The first focus of the lab is the use of experimental clinical trial methods to examine the effects of perimenstrual changes in estradiol, progesterone, and their neurosteroid metabolites (e.g., allopregnanolone) on acute suicide risk. Experimental data from Dr. Eisenlohr-Moul’s recently-completed K99 award indicates that perimenstrual hormone stabilization with transdermal estradiol and oral progesterone (vs. withdrawal under placebo) prevents the perimenstrual increases in suicidality observed in natural cycles under placebo (see Figure at right). Upcoming work will compare the effects of estradiol and progesterone stabilization, and will probe various potential mediators of these experimental effects, including neurosteroid metabolites of progesterone and immune signaling. This program of research may help to clarify the basic neurobiological mechanisms of acute changes in suicide risk for both females and males, and may eventually lead to the development of treatments that anticipate and prevent suicide attempts among at-risk individuals.
QUESTION 2 – WHAT ARE THE FUNDAMENTAL SUBTYPES OF CYCLICAL SYMPTOM CHANGE, AND HOW CAN WE BEST DIAGNOSE THEM?:
Different patterns of symptom change across the menstrual cycle may benefit from unique, targeted treatments. Therefore, the second focus of the laboratory is the identification, characterization, and reliable diagnosis of subtypes of psychiatric symptom change across the menstrual cycle. In the diagnostic arena, this includes the development of reliable methods for differential diagnosis of various cyclical disorders, including (1) the new DSM-5 diagnosis of premenstrual dysphoric disorder (PMDD), (2) perimenstrual exacerbation of underlying psychiatric disorder (e.g., borderline personality, ADHD, or substance abuse), and (3) PMDD with comorbid psychiatric diagnoses. During her fellowship in reproductive mood disorders, Dr. Eisenlohr-Moul developed and published the Carolina Premenstrual Assessment Scoring System (or C-PASS), the first fully standardized, computerized method for making the DSM-5 diagnosis of Premenstrual Dysphoric Disorder using two months of daily symptom ratings. Dr. Eisenlohr-Moul also works with large observational datasets of daily symptom and steroid/neurosteroid data to identify fundamental symptom timing dimensions (e.g., early luteal vs. late luteal symptom onset; see Figure above) and their unique pathophysiologic underpinnings. This work may inform the development of more targeted, timely treatments based on the reliable assessment of individual differences in cyclical symptom patterns.