Residence in High-Crime Neighborhoods Moderates the Association Between Interleukin 6 and Social and Nonsocial Reward Brain Responses

BACKGROUND: Residence in high-crime neighborhoods, especially in childhood, is linked to mental health issues later. Detecting distinct neurobiological processes underlying the effects of this environmental stressor may be critical to identifying prevention and intervention targets. This study examined the relationships of levels of a circulating inflammatory protein with social and monetary reward–related brain function among adolescents who lived in high- versus low-crime neighborhoods during childhood. METHODS: A total of 70 participants (mean age = 16.3 years; 57% female) completed measures of inflammatory markers, depression history, and health and 2 functional magnetic resonance imaging tasks assessing responsivity to monetary and social rewards. Multivariate linear regression tested whether individuals with higher interleukin 6, an inflammatory cytokine, who also lived in neighborhoods with higher crime had distinct orbitofrontal cortex and nucleus accumbens activation to monetary reward and social acceptance. RESULTS: For adolescents who lived in neighborhoods with more crime, higher interleukin 6 was associated with higher nucleus accumbens responses to social acceptance. We did not detect significant moderating effects of neighborhood crime rates on the associations of interleukin 6 with orbitofrontal cortex responses to social acceptance or orbitofrontal cortex/nucleus accumbens activation during monetary reward anticipation or outcome. These results were obtained before and after adjusting for neighborhood income and other covariates. We did not detect significant moderating effects of neighborhood income. CONCLUSIONS: High-threat residence environment and specific demands of the social context in childhood may have shaped the effect of peripheral immune activation on reward-related neural function in adolescence. The prevailing view that inflammation-associated behaviors are characterized by blunted responsiveness to reward may be oversimplistic.