The Biological Salience of Dimensions of Early Life Stress in Predicting Psychopathology

About This Grant

PROJECT SUMMARY/ABSTRACT Early life stress (ELS)—defined as experiences that threaten the fulfillment of an individual's basic needs leading to prolonged stress—is a well-established risk factor for the development of internalizing and externalizing psychopathology symptoms. Yet, the mechanisms through which ELS contributes to later mental health outcomes remain unclear. Guided by a biopsychosocial framework and informed by developmental psychopathology and behavioral genetics, the proposed project aims to clarify how ELS becomes biologically embedded to influence adolescent psychopathology. Research suggests that stress-responsive biological systems—such as the hypothalamic-pituitary-adrenal (HPA) axis, immune system, and epigenetic regulation— may serve as mechanistic pathways linking ELS to mental health outcomes, but these systems are rarely studied together, and genetic confounding is often unaddressed. This study leverages the Arizona Twin Project, an ongoing, longitudinal twin study representative of the southwestern United States, to address these gaps. The specific aims are to: (1) identify distinct dimensions of ELS and test whether they differentially predict internalizing and externalizing symptoms; (2) examine whether biological mechanisms—specifically hair cortisol concentration, inflammatory markers, and DNA methylation— mediate associations between ELS dimensions and adolescent psychopathology; and (3) use biometric twin modeling to estimate genetic and environmental contributions to these biological mechanisms and their associations with psychopathology. By modeling multiple forms of ELS and multiple biological systems in a genetically informed design, this project will enhance specificity in identifying modifiable mechanistic targets for prevention. The proposed training plan will support the applicant's development into an independent clinical scientist with expertise in developmental psychopathology, behavioral genetics, and biobehavioral mechanisms of stress. Under the guidance of an expert, interdisciplinary mentoring team, training goals include: (1) formal instruction and experiential training in biological data analysis (e.g., HPA axis, inflammation, epigenetics); (2) advanced training in quantitative methods, including longitudinal modeling and twin methods; (3) ongoing professional development in research ethics, dissemination and translation of findings, and career advancement. The fellowship will take place within the collaborative and interdisciplinary training environment at Arizona State University, under the mentorship of experts in developmental psychology, health psychology, neuroscience, and behavioral genetics. This NRSA fellowship will prepare the applicant for a research career focused on identifying modifiable biological mechanisms to inform personalized prevention and improve public health outcomes for youth exposed to ELS.