Depression in the pubertal transition: Circadian rhythms and sleep impairment as mechanisms of risk

2020 Award: $37,920

Puberty is characterized by dramatic reproductive hormone instability, sleep and circadian rhythm disturbances, and an increased risk for depression, especially for girls. This study will examine the role of estrogen fluctuation in regulating sleep and circadian rhythms to understand risk for female-dominated adolescent depression. The pubertal transition is a critical developmental window offering a unique opportunity for identifying novel treatment targets and intervention efforts to diverge mental illness trajectories.

Need/Problem: Adolescent girls have a three-fold greater risk for depression and a two-fold greater risk for sleep disorders compared with boys. The pubertal transition marks an abrupt divergence between the sexes in risk for depression and sleep disorders, implicating ovarian hormones (e.g., estrogen) as a common pathway of risk. With the prevalence of female adolescent depression rising, and earlier onset of depression predicting a more debilitating course of illness, identifying the causes of mood impairment in the pubertal transition will have a major public health impact.

Grant Summary: With the Foundation of Hope’s support, this research will use a novel multimodal approach to characterize the biobehavioral model by which estrogen impacts circadian rhythm dysregulation (melatonin and cortisol) and sleep pattern irregularity in the pubertal transition. This is a critical first step in identifying mechanisms of risk for female adolescent depression.

Goals and Projected Outcomes: Investigating the role of estrogen on circadian rhythms and sleep during the pubertal transition, and the moderating role of interpersonal stress, will provide mechanistic insight into the neurobiological basis of depression at a critical developmental window for intervention and prevention efforts. The primary goal of this research is to identify novel treatment targets and intervention approaches for the early detection and prediction of adolescent mood disorders.

Elizabeth Andersen, PhD

Grant Details: The pubertal transition is characterized by dramatic physical and psychological changes, including a developmental shift in the sleep-wake cycle, which is amplified in girls with depression. Sleep is critical for the refinement and maturation of brain networks and disruptions in sleep make the immature circuitry more vulnerable to stress. This is the first study to examine the role of estrogen in regulating circadian rhythms and sleep, and how these contribute to risk for depression in the pubertal transition. 56 mid-pubertal girls (within one-year post-menses onset) will be enrolled in the study. Following daily measurement of hormones and mood for one menstrual cycle, girls will complete a 1-week sleep and circadian rhythm assessment involving self-reported sleep and 24-hour objective sleep monitoring using wrist actigraphy, and serial cortisol and melatonin collections for 4 days to capture circadian rhythms. Greater estrogen variability is expected to predict dysregulated sleep and circadian rhythms and, in turn, elevated symptoms of depression, especially in girls with high interpersonal stress.