Psychobiological Mechanisms Underlying the Association Between Early Life Stress and Depression Across Adolescence

Abstract More than 50% of youth will experience at least one form of significant adversity in early life. Such adversities pose significant risk not only for the development of psychopathology over the life course, but also for attempted suicide, a leading cause of death in people ages 10-24 years. We have recruited and assessed 220 9- to 13-year-old boys and girls across four timepoints, each two years apart, to examine the effects of exposure to ELS on trajectories of stress reactivity and reward sensitivity, and, in turn, their impact on the onset of psychopathology and suicidal behaviors across adolescence. In this cohort we have conducted repeated measurements of symptoms and diagnoses of psychopathology, neural, endocrine, cognitive, immunological, and behavioral assessments of stress reactivity and reward sensitivity, and early exposure to adversity, including the type, severity, and timing of stressful events. We have published a series of papers from this project elucidating the effects of ELS on psychobiological functioning, trajectories of brain development, and biological aging, and the consequences of these alterations for clinical functioning. In this MERIT renewal application, we propose to build on and extend our work in three important ways. First, we will conduct an additional assessment of our participants at age 20 in order to examine the effects of ELS on trajectories of neurodevelopment and clinical outcomes from childhood to young adulthood, as well as the persistence of COVID-19 pandemic-related difficulties in mental health, stress, and brain metrics. We will also extend our examination of how environmental pollutants and conditions affect relations among these variables. Second, we will extend and replicate our findings in a younger, non-Western sample by analyzing data from the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) project, an ongoing prospective study in which many of the same, or comparable, measures that we administered in our project have also been collected regularly from approximately 1,500 parents and children since the prenatal period. Extending and replicating our findings with the GUSTO dataset, which includes younger, non-Western children from Southeast Asian families in Singapore, will complement findings from other large cohorts, like ABCD and NCANDA, that have assessed only Western participants. Finally, will leverage our own and GUSTO data to examine the effects of the COVID-19 pandemic shutdown on children's and adolescents' psychobiological functioning. In both datasets we have a unique opportunity to compare comprehensive psychobiological data collected from the same youth before and after the pandemic shutdowns in order not only to examine how the pandemic has altered young people's psychobiological functioning and development, but importantly, to also identify risk and resilience factors across cultural contexts. Further, the new proposed adult assessment in our ELS project will allow us to examine the persistence of COVID-related difficulties by re-assessing participants whom we studied soon after pandemic quarantine restrictions ended.