Mechanisms of Depression and Anhedonia in Adolescents: Linking Sleep Duration and Timing to Reward- and Stress-Related Brain Function

7. PROJECT SUMMARY/ABSTRACT
The long-term objectives of this proposal are: 1) to evaluate a biobehavioral model of depressive symptoms
and anhedonia in adolescents, and 2) to leverage sleep and circadian function to promote mental health.
These objectives are consistent with two key priorities of the National Institute of Mental Health (NIMH): 1)
identify mechanisms of psychopathology, and 2) improve prevention and treatment for psychopathology. The
proposed model of depression posits that sleep duration and/or timing moderate the effects of stressful events
on depressive symptoms and anhedonia by disrupting reward- and stress-related brain function. The research
approach uses two complementary study designs to evaluate the proposed model: 1) an observational study
(n=150) that assesses the degree to which short and late sleep predict reward- and stress-related brain
function and depressive symptoms and anhedonia, and 2) an experimental study (n=100) that assesses the
extent to which sleep duration and timing impact reward- and stress-related brain function and depressive
symptoms and anhedonia. The sample includes high-school adolescents (14-19 years of age) with enhanced
risk for depressive symptoms based on exposure to lifetime stressful events and current depressive symptoms.
Recruitment will be stratified to include adolescents with short and late sleep (weekday sleep duration ≤ 6 h &
midpoint ≥ 4 am; n=100) versus long and early sleep (weekday sleep duration ≥ 8 h & midpoint ≤ 2:30 am;
n=50). Both studies include measurement of daily sleep and stressful events for 2 weeks; laboratory measures
of reward- and stress-related brain function and sleep and circadian characteristics; self-report measures of
lifetime stressful events; and self-report measures of depressive symptoms and anhedonia during daily and
weekly monitoring. The experimental study includes random assignment of adolescents with short and late
sleep from the observational study to 2 weeks of either: 1) 90 min extension and advance of sleep opportunity
and timing (n=50); or 2) typical sleep opportunity and timing (n=50). This research approach is designed to
accomplish three specific aims: 1) Evaluate the extent to which sleep duration and/or timing predict reward-
and stress-related brain function, and moderate the effects of stressful life events; 2) Establish the extent to
which sleep duration and/or timing impact reward- and stress-related brain function, and moderate the effects
of stressful life events; and 3) Determine the extent to which changes in reward- or stress-related brain function
mediate the associations between sleep duration and/or timing and later depressive symptoms and anhedonia.
The investigative team has expertise in the etiology and prevention of depression in adolescents, including
specific expertise in the impact of sleep and stressful life events on the stress and reward systems that
contribute to depression and anhedonia. All four investigators are also licensed clinical psychologists who are
committed to translating research on the mechanisms of psychopathology to preventative interventions.

Grant Number: 5R01MH126109-04
NIH Institute/Center: NIH
Principal Investigator: Melynda Casement