Inflammation, fronto-amygdala connectivity, and negative affective reactivity to daily stress in adolescents

Maladaptive affective responses to daily stress in adolescence are a robust risk factor for the development of psychopathology. Importantly, however, adolescents vary widely in the magnitude of their affective reactivity to stress. Although peripheral inflammation and fronto-amygdala circuitry during emotion regulation are both plausible biological contributors to this variability, no study has yet integrated inflammatory markers, neural metrics of emotion regulation, and real-world assessments of stress and affect to examine how these systems interact to shape affective reactivity to stress in adolescents' daily life.

Adolescents (N = 124; 60% female) aged 13.07-20.10 years (M = 16.20) completed a 14-day ecological momentary assessment (EMA) protocol assessing stressor occurrence, stress severity, and momentary affect. A subset of participants provided peripheral blood samples assayed for C-reactive protein (CRP) to index systemic inflammation (N = 85), and a further subset completed an fMRI affect-labeling task to quantify task-related functional connectivity between the amygdala and lateral prefrontal cortex (LPFC; N = 68). Multilevel models tested whether higher CRP predicted stronger within-person coupling of stress and negative affect (NA), and whether LPFC-amygdala connectivity moderated this association.

Higher stress severity predicted higher NA, and greater inflammation potentiated these stress-related increases in NA. A three-way interaction with DLPFC-amygdala connectivity may further moderate this association, but the effect did not survive correction for multiple comparisons, and the sample was underpowered to test it reliably.

Inflammation was linked to stronger coupling of daily stress and negative affect in adolescents. Whether fronto-amygdala connectivity adds to this remains untested at adequate power.