Traces of trauma: The lasting imprint of childhood trauma on affective and cardiometabolic health

Childhood trauma is a well-known risk factor for poor health later in life. It is often defined as the experience of physical, emotional, or sexual abuse, or neglect during childhood. Beyond its direct link to individual diseases, childhood trauma may contribute to the development of multiple, co-occurring diseases, a phenomenon known as comorbidity. Specifically, depression and cardiometabolic diseases often appear to be comorbid: people with depression are more likely to develop cardiometabolic diseases, and vice versa. Because this combination greatly increases the burden on individuals and society, understanding how comorbid depression and cardiometabolic disease is crucial. This PhD dissertation investigates the connection between childhood trauma, depression, cardiometabolic disease, and their comorbidity. It explores factors heightening disease risk and uncovers potential biological mechanisms linking childhood trauma to diseases. Using an epidemiological approach, the research presented in this dissertation analyzes large-scale observational data from multiple cohorts and biobanks. A key part of the research was conducted within the EarlyCause consortium, a collaborative effort of 13 European research institutions focused on understanding how early-life stress leads to comorbid depression and cardiometabolic disease. By pooling data from several studies and applying advanced meta-analytic techniques, this partnership enabled analyses involving hundreds of thousands of participants, increasing the reliability and generalizability of the findings across different European populations, including both general and clinical groups. All chapters also include data from the Netherlands Study of Depression and Anxiety, a richly detailed dataset with repeated measures of childhood trauma, depressive symptoms, somatic diseases, body measurements, and blood-based metabolite profiles over time. The findings reveal that childhood trauma is strongly associated not only with depression and cardiometabolic disease individually but even more so with their comorbidity in adulthood. Those who experienced severe trauma in childhood face especially high risks. Childhood trauma also correlates with persistently elevated cardiometabolic risk throughout adulthood, particularly when depression is present. Moreover, trauma is linked to distinct metabolomic patterns, suggesting biological pathways involving disruptions in amino acid and fatty acid metabolism, as well as an altered stress response, which may explain the increased disease risk. In sum, childhood trauma is a consistent predictor of poor mental and cardiometabolic health later in life, with especially high odds of having both diseases together likely driven by interrelated mechanisms. These insights highlight the urgent need for preventive measures against childhood trauma. Social policies and clinical interventions aimed at reducing childhood trauma could lower the future burden of associated diseases. When prevention is not possible, early monitoring and timely intervention for those with trauma histories may help mitigate the development of depression, cardiometabolic disease, and their comorbidity.