Project Summary Background. Latino adolescents have higher prevalence of alcohol consumption and binge drinking, start using drugs and alcohol earlier, and are at greater risk of developing addiction due to early use. It has been well documented that adverse childhood experiences (ACEs), such as abuse and neglect, significantly increase the risk for alcohol misuse. ACEs also affect HPA axis functioning and alter cortisol levels that can lead to mental health problems and alcohol use. More recently, epigenetic studies have uncovered that methylation of HPA axis genes affect cortisol levels and increase the risk for alcohol use disorder. More integrative research is needed to understand how biological and environmental factors interact to increase the vulnerability for alcohol misuse. Research Strategy. To obtain a more nuanced understanding of mechanisms leading to alcohol misuse, we hypothesize influences at the psychological (traumatic stressors), biological (genetics, endocrine), interpersonal (family cohesion), and cultural (values) level and identify paths of risk and resilience. The current project will assess the impact of ACEs on alcohol abuse and identify relevant protective factors (aim 1), evaluate the role of HPA axis functioning (hair cortisol) in the ACEs-alcohol misuse link and identify relevant protective factors (aim 2), and explore epigenetic mechanisms (saliva DNA methylation) linking ACEs and HPA axis functioning (hair cortisol; aim 3). The proposed study will leverage the structure and resources of the candidate primary mentor’s parent R01 and select a subsample of Latino adolescents (N= 150), for stress biomarkers collection (i.e., hair cortisol, saliva DNA methylation). Data yielded from the proposed study will lead to a future R01 examining the contribution of childhood adversities on biological vulnerabilities for alcohol use disorders longitudinally. Training Plan. In coordination with the research plan, the candidate will pursue training in the following three areas: (1) obtain training on alcohol epidemiology and etiology as a foundation to developing addiction prevention research with racial/ethnic minorities, (2) gain knowledge of epigenetics via DNA methylation, particularly in HPA axis and alcoholism-related genes, and (3) train in statistical genetics. Mentorship. Dr. Alegría is an expert in health and substance use disparities with extensive experience in mentoring early career investigators. Co-mentor Dr. Shields provides expertise on adversity-related epigenetics among minorities, co-mentor Dr. Zhang provides expertise in epigenetic influences in alcohol use disorders, and co-mentor Dr. Becker provides expertise in alcohol addiction among adolescents. A team of advisors provides additional expertise in biostatistics modeling of longitudinal data (Dr. Spiegelman) and in the impact of adversity on child endocrinology (Dr. Valentino). Candidate. The candidate is an early career scientist and clinical psychologist w...