Resting-State Functional Connectivity of the Central Executive Network Moderates the Relationship Between Neighborhood Violence and Proinflammatory Phenotype in Children.

Abstract Background Neighborhood violence increases children’s risk for a variety of health problems. Yet, little is known about biological pathways involved or neural mechanisms that might render children more or less vulnerable. Here, we address these questions by considering whether neighborhood violence is associated with the expression of a proinflammatory phenotype and whether this relationship is moderated by resting-state functional connectivity (rsFC) of the central executive network (CEN). Methods The study involved 217 children (13.9 years old; 66.4% female; 36.9% Black; 30.9% Latinx), enrolled in eighth grade and reassessed 2 years later. At time 1, geocoding was used to estimate murder frequency in children’s neighborhoods, and functional magnetic resonance imaging was used to characterize CEN rsFC. At both visits, children gave antecubital blood for ex vivo studies, where leukocytes were incubated with stimulators and inhibitors of inflammation, and cytokine production was measured. Results Consistent with our hypotheses, the relationship between neighborhood murder and inflammatory activity was moderated by CEN rsFC. Among children with lower rsFC, neighborhood violence covaried with a proinflammatory phenotype, reflected in larger cytokine responses to triggering stimuli and lower sensitivity to inhibitory agents. These associations were generally not apparent for children with higher rsFC, although occasionally they ran in the opposite direction. The same patterns were apparent 2 years later. Conclusions These results advance the understanding of neighborhood violence and its relationship with processes involved in the initiation and resolution of inflammation. They also deepen understanding of variability in children’s immunologic responses to stress and suggest that the CEN may be a neurobiological contributor to resilience.