Early life stress, systemic inflammation, and neural correlates of implicit emotion regulation in adolescents

Exposure to early life stress (ELS) increases the risk for developing psychopathology; however, the mechanisms underlying this association are not clear. In this study we examined systemic inflammation as a pathway that may link exposure to stress to altered neural correlates of implicit emotion regulation in adolescents with varying levels of exposure to ELS (n = 83; 52 females, 31 males; 15.63 +/- 1.10 years). We measured ventrolateral prefrontal cortex (vlPFC) activation and functional connectivity (FC) between the bilateral amygdala and the vlPFC as adolescents completed an affect labeling task in the scanner and assessed concentrations of C-reactive protein (CRP) using a dried blood spot protocol. We found that CRP levels were negatively associated with vlPFC activation during implicit regulation of negatively-valenced stimuli, and that cumulative severity of ELS exposure moderated this neuroimmune association. Severity of ELS also significantly moderated the association between CRP levels and FC between the bilateral amygdala and L-vlPFC during implicit emotion regulation: in adolescents who had been exposed to more severe ELS, higher CRP was associated with more negative frontoamygdala FC during implicit regulation of negatively-valenced stimuli. Thus, ELS may disrupt the normative association between the immune system and the neural processes that underlie socioemotional functioning potentially increasing adolescents' risk for maladaptive outcomes.