Project Summary COVID-19 is an unprecedented global pandemic. Research from previous large-scale, community traumas (e.g, natural disasters) and epidemics have documented a rise in mental health concerns during such crises, and for some, persisting effects. For families having children with Down syndrome (DS), the effects of COVID- 19 may be especially salient due to underlying medical conditions associated with poorer course, fears of medical rationing, loss of routines, structure, loss of developmental services, and social isolation. Together these factors create a “perfect storm” of risk for depression, anxiety, and behavioral conditions in people with DS that may have long-term consequences for mental and physical health of people with DS. Experts have called for surveillance studies to monitor the impact of COVID-19 to inform stepped care so that those at highest risk for psychological sequalae receive needed resources. The original scope of the parent award (K08HD092610) was focused on the assessment and evaluation of the associations between exposure to stressful life events, depression, and other markers of mental health in people with DS aged 12-45, along with the identification of biomarkers of depression in this population. This supplemental project will provide the opportunity to examine the impact of COVID-19-related stressors (e.g., job loss, social isolation, infection) on the health and wellbeing of caregivers and people with DS, including measures of depression, anxiety, adaptive behavior, and cognitive decline. The specific aims of the project are to: 1) conduct a mental health surveillance study (n = 900) to identify acute COVID-19 pandemic impacts on caregiver stress and mental health outcomes of people with DS, and to assess their trajectory over time (i.e., 2, 4, and 6 month follow up); 2) conduct deep psychiatric phenotyping (e.g., depression, anxiety, cognitive decline, adaptive functioning) and buccal cell sampling of the people with DS from the surveillance study reporting the highest (n = 25) and lowest (n = 25) COVID-related stress; and 3) examine acquired genetic/chromosomal instability, as measured by DNA methylation, telomere length, and micronuclei frequency, as a mediator between COVID-19 related stress and mental health outcomes. The original scope of the training plan of this career development award was designed to support the candidate's long-term goal of conducting genomically-informed traumatic stress research in people with DS and other forms of intellectual disability with training in DS-related developmental and psychiatric phenotypes, statistics, and epigenetic biomarkers. An additional mentor, Nicole Baumer, MD, Director of Boston Children's Hospital Down Syndrome Program, has been added to the mentorship team. Dr. Baumer is a leader in the international response to COVID-19 in people with Down syndrome (e.g., T21 Research Society COVID-19 Survey, Q&A on COVID and Down Syndrome) will bring valuable i...