Annual Research Review: Social relationships and the immune system during development.

A child's social relationships serve critical functions during development. The interface between a child's social world and their immune system, particularly innate immunity, which helped children survive in the face of infections, nutritional scarcity, and violence throughout human history, is the focus of this Annual Research Review. This article reviews the state of research on social relationships and innate immune inflammation during childhood. Warmth and rejection in childhood social relationships, as well as physical trauma and unpredictable social environments, were not consistently related to circulating inflammatory markers such as interleukin-6 and C-reactive protein during childhood. Instead, links between social environments and inflammation were observed in studies that focus on children with greater background risk factors, such as low family socioeconomic status, family history of mood disorders, or presence of chronic interpersonal stressors combined with acute episodic stressors. In addition, studies on worse childhood social environments and greater inflammation in adulthood were more consistent. Warmth and rejection in the social environment may be related to sensitivity of immune cells to the anti-inflammatory actions of glucocorticoids, though this is primarily observed in adolescent women at risk for depression. Additional mechanistic evidence suggests that greater warmth and less rejection are related to processes that regulate inflammation, including greater expression of the glucocorticoid receptor gene and lower expression of genes that are responsive to the pro-inflammatory transcription factor NF-kappa B. The article concludes by discussing implications of the interface between a child's social relationships and inflammation for mental health and other recent (on evolutionary timescales) health threats, as well as recommendations for future research, and recommendations for researchers interested in integrating inflammatory measures in developmental research.