Oxidative stress as Mediator between Adverse Childhood Experiences and Mental Health Problems in the JAEL high risk cohort of young care leavers

• Applicant: Professorin Dr. Vera Clemens
• Subject Area: Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry ; Developmental Neurobiology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 469190220

Adverse childhood experiences (ACEs) are well-known risk factors for mental disorders. There is growing evidence supporting that dysregulation of hypothalamic-pituitary-adrenal (HPA) stress axis and inflammatory processes mediate the pathway between ACEs and health problems. However, little is known about underlying mechanisms and how interactions between HPA stress axis and inflammation culminate in such dire consequences. One missing key may be oxidative stress (OS), which has been shown to closely interact with both HPA and inflammation in mental disorders. The brain is very sensitive to OS, particularly during development. This project aims to evaluate the role of OS in the development of mental disorders following ACEs in a well-characterized study cohort of young adults, who have been living in institutional care during their adolescence (JAEL study). Children and adolescents in residential care institutions are at high risk for both – ACEs and mental disorders. The Child and Adolescent Psychiatric Hospitals of the Universities of Basel and Ulm examined a sample of 592 youths (t0, mean age 16.1) from Swiss residential care institutions. At t2, 132 representative care leavers (mean age= 26.1 years) were followed up and biosamples were taken. Recruitment at t2 has finished in July 2020. Using the unique advantages of this high-risk, extensively assessed cohort, objectives of this project are 1) to test whether OS status alterations mediate the effects of ACEs on mental health, and 2) to analyze the interplay between OS and other neurobiological parameters including inflammation, telomeres and HPA axis activation. This project will benefit from the joint expertise of our 3 centers: Ulm (trauma), Basel (JAEL cohort) and Lausanne (OS status alterations). This 3-year research project will provide more insights into biological mechanisms involved in mental disorders following ACEs, paving the way to mechanism-based biomarkers, which is a crucial step to improve early detection as well as the development of specific interventions for the prevention of mental health disorders in youth.

• DFG Programme: Research Grants
• International Connection: Switzerland
• Partner Organisation: Schweizerischer Nationalfonds (SNF)
• Cooperation Partners: Dr. Paul Klauser; Dr. Marc Schmid