Associations between brain function during fear learning and inflammatory levels: The moderating roles of early and late maltreatment

Fear learning is a core adaptive process. Although growing evidence indicates that associations between inflammation and both brain structure and reward-related function can be moderated by early risk factors, it remains unclear whether childhood maltreatment moderates links between inflammation and brain function during fear learning. We tested this question in young adults (n = 128; 72 female, 56 male; mean age = 21.31 years, SD = 2.52; range = 17–28). Childhood maltreatment was assessed retrospectively as abuse and neglect during early childhood (ages 0–11) and late childhood (ages 12–18). Inflammation was indexed by interleukin-8 (IL-8) and interleukin-17 (IL-17), log-transformed and standardized. Functional MRI measured brain activation and connectivity during fear learning. Early abuse moderated the association between amygdala activation and IL-8 levels, and late neglect moderated the association between ventromedial prefrontal cortex (vmPFC) activation and IL-8 levels. Early neglect also significantly moderated the association between amygdala–vmPFC connectivity and IL-17 levels. To our knowledge, this is the first evidence that the type and timing of childhood maltreatment jointly shape brain–immune relationships during fear learning. These findings advance understanding of how early adversity may confer risk for physical and mental health problems by altering interactions between neural circuits and inflammatory processes.