Abstract / Summary
Abstract Background Mental illnesses are on the rise, highlighting the urgent need for preventive measures. However, preventive programmes show slow to moderate effects that diminish over time, potentially due to limited knowledge of mechanisms underlying resilience. Despite growing evidence on risk and resilience factors for the development of mental illness, their relative importance and dynamic interplay under real-time conditions, such as acute stress, remain unclear. Method This study investigates biological and psychological risk and resilience factors for the development of mental illness, focusing on individuals’ capacity to cope with stress, using an innovative mixed-methods twin-family design. Analyses will integrate the mixed-methods and twin-family structure and will primarily be exploratory and hypothesis-generating, given the expected sample size. The study will include N = 50 monozygotic and dizygotic twin pairs and, where available, their non-twin siblings aged 16 years and older. It comprises two complementary parts: (1) a laboratory assessment including self-report questionnaires, an experimental stress task, physiological monitoring, and biological sampling; and (2) a one-week intensive longitudinal ambulatory assessment including repeated measures of emotional states and perceived stress, audio diaries, nocturnal ECG recordings, and saliva samples. Biological factors (epigenetic markers, stress reactivity), psychological factors (childhood experiences, emotion regulation, perceived stress), social factors (social networks, family support), and background factors (parental health, socioeconomic status) will be assessed across both parts. Laboratory and ambulatory data will be integrated to examine trait-level risk and resilience factors and state-level dynamic processes. Comparisons between monozygotic and dizygotic twins and non-twin siblings will allow estimation of genetic and environmental contributions to stress coping and mental health outcomes. Discussion The study will provide novel insights into interactions between biological, psychological, and social risk and resilience factors in shaping mental health. By combining laboratory-based stress assessment, real-time ambulatory data, and a twin-family design, it aims to advance understanding of stress-related and transgenerational mechanisms. Trial registration The study was approved by the ethics committee of the University and University Hospital of Tübingen (No. 737/2023BO1) and was conducted in accordance with the ICH-GCP guidelines, the Declaration of Helsinki, and applicable legal requirements. The study was retrospectively registered in the German Clinical Trials Register (DRKS; DRKS00033660) on July 14, 2026 (https://www.drks.de/DRKS00033660).