PROJECT SUMMARY/ABSTRACT
Approximately 1 in 3 reproductive aged women and girls suffer from migraine, the most disabling disease of
this demographic worldwide. Affective disorders are 2-3 times more common among migraineurs, and
migraineurs with psychiatric comorbidity report more functional impairment and worse quality of life than
migraineurs without psychiatric conditions. Despite the high prevalence of this comorbidity and evidence of
shared pathophysiology, the association between migraine and affective disorders remains largely unexplored.
Fluctuations in female sex hormone levels play a significant role in migraine and affective disorder
presentations and are particularly volatile across the menstrual cycle and during reproductive life transitions
(puberty, postpartum, menopause); however, the longitudinal relationship between migraines and affective
disorders across the life course has not been studied. Up to two-thirds of female migraineurs experience
menstrual migraine and half of women with affective disorders report premenstrual exacerbation of anxiety and
depression. However, migraine has not been studied as a risk factor for premenstrual syndrome/premenstrual
dysphoric disorder or as a marker of increased hormonal sensitivity among women with anxiety or depression.
The objective of this research is to collect and analyze detailed longitudinal data on migraine and mental
health symptoms to establish migraineurs as a unique phenotype of individuals with affective disorders due to
their vulnerability to hormonal fluctuations. In Aim 1, Dr. Crowe will determine the longitudinal association
between migraine and affective disorders across the lifespan with an emphasis on hormonal transitions using
data from the Nurses’ Health Study cohorts. In Aims 2 and 3, she will focus her work on hormonal fluctuations
across the menstrual cycle. She will design and implement a sub-study in the Nurses’ Health Study 3 and
Growing Up Today Study cohorts using smartphone data and ecological momentary analysis to estimate the
relationship between migraine (menstrual and overall) and premenstrual syndrome/premenstrual dysphoric
disorders (Aim 2). Dr. Crowe will also collect data on affective disorder symptom variability across the
menstrual cycle among migraineurs, compared to non-migraineurs (Aim 3). To carry out this research, Dr.
Crowe will receive training and mentorship from a team with expertise in epidemiological measurement of
affective disorders, smartphone digital phenotyping, and modeling of high-dimensional longitudinal data. She
will also draw on the myriad professional resources available at Brigham and Women’s Hospital, Harvard
Medical School, and Harvard T.H. Chan School of Public Health. Altogether, the proposed research and
training will improve affective disorder risk assessment and screening, inform treatment for those with
comorbid affective disorders and migraine and prepare Dr. Crowe with the skills and preliminary data to
become an independent researcher at the intersection of mental health and reproductive epidemiology.