Alterations in reward responsiveness represent a key mechanism implicated in youth depression risk. However, not all youth with these alterations develop depression, suggesting the presence of factors that may moderate risk patterns. As socioeconomic disadvantage is also related to youth depression risk, particularly for youth exhibiting altered reward function, this study examined whether indices of family- and neighborhood-level disadvantage interacted with electrocortical reward responsivity to predict depression symptom trajectories across childhood and adolescence.

Participants included 76 youth (ages 9–16 years) at low and high risk for depression based on maternal history of depression. At baseline, youth completed a monetary reward-guessing task while electroencephalography was recorded to measure the reward positivity (RewP), an event-related potential indexing reward responsiveness. Family and neighborhood disadvantage were assessed using the income-to-needs (ITN) ratio and Area Deprivation Index (ADI), respectively. Self-reported and clinician-rated depression symptoms were assessed across a multiwave, 18-month follow-up.

RewP interacted with family- and neighborhood-level disadvantage to predict self-reported depression symptom trajectories. Specifically, blunted RewP predicted self-reported depression symptom increases for youth with a lower ITN ratio and higher ADI score. A blunted RewP also predicted clinician-rated depression symptom increases for youth living in neighborhoods with higher ADI scores.

Findings suggest that reduced reward responsiveness is a mechanism implicated in future depression risk among youth, specifically in the context of family- and neighborhood-level socioeconomic disadvantage. Interventions that enhance reward response among youth exposed to higher levels of socioeconomic disadvantage may be particularly effective in preventing depression emergence.

Depression is characterized by divergent changes in positive and negative affect. Emerging roles of inflammation in depression portend avenues for novel immunomodulator-based monotherapy, targeting mechanistically distinct symptoms such as anhedonia and pessimism.

To investigate links between these divergent affective components and inflammation, we used a probabilistic reinforcement-learning fMRI paradigm, testing for evidence of hyposensitivity to reward, and hypersensitivity to punishment in low-inflammation depression cases (loCRP depression; CRP ≤ 3 mg/L; N = 48), high-inflammation depression cases (hiCRP depression; CRP > 3 mg/L; N = 31), and healthy controls (HC; CRP ≤ 3 mg/L; N = 45). We aimed to (i) determine whether depression cases with high and low inflammation showed aberrant neural activation to monetary gains and losses compared to controls, and (ii) examine if these alterations correlated with a continuous measure of C-reactive protein (CRP) in depression, as well as indices of anhedonia and pessimism derived from behavioral instruments in depression.

Voxel-wise activation was observed in key brain regions sensitive to monetary reward (ventromedial prefrontal cortex, vmPFC; nucleus accumbens, NAc) and punishment (insula) outcomes across all three groups. However, there was no significant difference in activation between groups. Within depression cases, increasing CRP scaled negatively with activation in the right vmPFC and left NAc but not insula cortex. However, there was no significant association between regional activation and severity of anhedonia or pessimism.

Our results support the previously reported association between CRP and striatal reward reactivity in depression but do not extend this to processing of negatively valenced information.