Adverse childhood experiences (ACEs, e.g. family violence, parental mental health problems, bullying) carry a higher risk of anxiety-related disorders, yet the underlying mechanisms remain unclear. We will use cohort studies in the UK and Brazil to assess the mechanisms linking ACEs to anxiety-related disorders.

The depth and breadth of measurements in the cohorts enables us to examine: 1) multiple levels of explanation: social, cognitive, psychological, biological, plus within- and between-level interactions, 2) the developmental trajectory of onset and persistence of anxiety, and how this can be prevented or interrupted, 3) the role of commonly co-occurring conditions (e.g. depression, neurodivergence), and 4) consistency/specificity of mechanisms across ACEs and anxiety-related disorders.

Comparisons across generations and the UK and Brazil, where social contexts and levels of ACEs vary, will enable assessment of the degree to which interventions need to be culturally/generationally specific.

Multiple analysis approaches will support causal inference: difference-in-difference, sensitivity analyses to assess environmental and genetic confounding, and causal mediation analysis. Where possible, we will triangulate cohort analyses with Mendelian randomization studies using large biobanks.

The research has been co-designed, and will be co-produced by, UK-based people with lived experience of anxiety. We will develop and evaluate lived experience involvement in Brazil.