Value-based cognitive control moderates the relation of inflammation with depression in adolescents

Depression has been linked to both elevated systemic inflammation and altered brain function related to reward processing and cognitive control. We know little, however, about how these factors jointly confer risk for this disorder, especially during adolescence, when depressive symptoms typically emerge. In this study, we examined brain function during an incentivized go/no-go task in a community sample of 100 adolescents (mean [SD] = 15.8 [1.1] years). We assessed neural activation and task-dependent functional connectivity using a psychophysiological interaction analysis during the contrast of High Value > Low Value targets in two regions: the ventral striatum (VS) and ventrolateral prefrontal cortex (vlPFC). We hypothesized that activation and functional connectivity in these regions would moderate the association between C-reactive protein (CRP) and depressive symptoms. Regression analyses yielded a significant interaction (β = -0.29; P = .009): in youth with attenuated VS activation, increased CRP was associated with higher symptoms; this pattern was reversed in adolescents with even modest VS activation. No similar effects were obtained with the vlPFC or functional connectivity. Thus, striatal activation during value-based cognitive control may shape how inflammation relates to depressive symptoms in adolescents, underscoring the importance of elucidating the functioning of reward circuitry during this sensitive developmental period.