A brief historic review of research on early life stress and inflammation across the lifespan.

Background: Substantial evidence from epidemiological and clinical studies suggests that exposure to stress during sensitive developmental periods strongly and robustly increases the risk for psychiatric and physical disorders, resulting in reduced longevity. Chronic immune activation has been proposed as one mechanism through which early adverse experiences may become biologically embedded. This paper highlights selected key findings and questions that first emerged in the literature and founded the field and then examines how research methods and questions have evolved over time.

Summary: During the past decades, evidence from preclinical, clinical, and epidemiological studies has accumulated suggesting consequences of early life stress (ELS) exposure for immune function, particularly increased chronic inflammation or inflammatory responses. Scientific approaches to study the effects of ELS on the immune system have changed since the first studies on this topic were published.

Key messages: Across different study designs, species and methods, a consistent association between childhood adversity and a proinflammatory phenotype has been reported. We critically discuss which topics warrant further consideration and how current findings could be used to develop targeted interventions to prevent or reverse the biological embedding of ELS and resultant disease manifestations.