Tracking the dynamic trajectory of behavioral, physiological, and neurobiological stress responses in female adolescents at high and low familial risk for depression. - Project Summary/Abstract. Stress and a parental history of Major Depressive Disorder (MDD) are among the most potent risk factors for future MDD development. Evidence suggests that the offspring of parents with MDD are especially vulnerable to the development of maladaptive responses to stress. Early adolescence is a critical window for studying MDD risk, as this developmental stage is just prior to the peak period of initial MDD onsets and a time of enhanced stress sensitivity, especially among females. Despite the importance of stress in MDD onset, the neural mechanisms underlying stress responses in female adolescents at high familial risk for MDD remain unclear. Furthermore, little is known about how stress-induced brain network changes may be linked to physiological and behavioral responses to stress and be predictive of future MDD onset. In this R01 resubmission, we aim to test a model in which having a parental history of MDD increases the risk for dysfunctional dynamic default mode network (DMN) – Central Executive Network (CEN) stress responses, two networks consistently linked to MDD pathophysiology and stress responsivity, prior to the onset of depression. Specifically, we expect that adolescents with versus without a parental MDD history will spend more time and persist longer in a DMN-CEN co-activated pattern in response to stress. We further hypothesize that this maladaptive DMN-CEN pattern will predict maladaptive psychophysiological and behavioral responses seen in the adolescents’ natural environment. Together, we expect that this stress sensitive profile of dysfunctional dynamic DMN-CEN, psychophysiological, and behavioral responses will predict future depression onset. We focus on DMN-CEN dynamics given accumulating evidence showing that, relative to static network properties, brain network dynamic properties may be more robustly associated with MDD pathophysiology as well as the behavioral and psychophysiological processes impacted by stress and MDD. In the PI’s own published work, adults with MDD as well as healthy adolescents with a maternal history of MDD spent more time and persisted longer in a DMN-CEN co-activated pattern relative to healthy controls and adolescents without a parental MDD history, respectively. Moreover, longer DMN-CEN persistence prospectively predicted greater perceived stress among the high-risk adolescents. This suggests that dynamic DMN-CEN properties may be a critical premorbid MDD vulnerability marker that could aid in the identification of adolescents vulnerable to future MDD onset. Building on an extensive set of preliminary data, we will investigate changes in DMN-CEN dynamic properties from before and after an acute psychosocial stressor, along with changes in heart rate (HR), heart rate variability (HRV), skin conductance (SC), and cortisol output in a sample of 148 13–15-year-old unaffected females with (n = 74) and without (n = 74) a parental history of MDD. Wearable and smartphone technology will be used to track daily stress vulnerability markers (HR, HRV, SC, sleep disturbances, perceived stress, stress-reactive rumination) every 6 months during an 18-month follow-up.
