Sleep duration moderates the associations between immune markers and corticolimbic function during stress in adolescents

Adolescence is characterized by biological changes in hormonal and circadian systems that, with concurrent psychosocial changes, result in increased sleep disturbances and stress sensitivity. Sleep disturbance has been associated with heightened stress sensitivity and elevated levels of inflammation in adults and adolescents, yet the neural correlates are unknown in adolescents. The current study investigated whether and how individual differences in peripheral immune markers (IL-6, TNF-alpha) related to neural response to stress in adolescents and whether these immune-brain associations were moderated by adolescents' sleep duration. Thirty-seven adoles-cents (14-15 years) who met quality control criteria for fMRI reported daily sleep duration for 7 days and performed a fMRI stressor task. A subsample of 23 adolescents additionally provided blood samples that were assayed for inflammatory markers using a multiplex assay. Results revealed that average sleep duration moderated associations between TNF-alpha and medial frontolimbic circuitry (amygdala, medial prefrontal cortex) during the stressor task such that, among adolescents who reported shorter sleep duration, higher levels of TNF-alpha were associated with greater deactivation in those regions during stress, which was associated with greater self -reported anxiety. These findings suggest that insufficient sleep duration coupled with greater levels of peripheral inflammation may promote a neural profile characterized by alterations in frontolimbic circuitry during stress, which can exacerbate sleep disturbances and/or peripheral inflammation.