Higher inflammatory proteins predict future depressive symptom severity among adolescents with lower emotional clarity.

BACKGROUND: A growing body of work has implicated inflammation in the pathogenesis of depression. As not all individuals with heightened levels of peripheral inflammation develop symptoms of depression, additional work is needed to identify other factors that catalyze the relationship between inflammation and depressive symptoms. Given that elevated levels of inflammatory activity can induce a variety of emotional changes, the present study examined whether emotional clarity, the trait-like ability to identify, discern, and express one's emotions, influences the strength of the association between inflammatory signaling and concurrent and prospective symptoms of depression. METHODS: Community adolescents (N = 225, Mage = 16.63 years), drawn from a larger longitudinal project investigating sex and racial differences in depression onset, provided blood samples to determine peripheral levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP) at a baseline visit, along with self-report measures of emotional clarity and depressive symptom severity. Depressive symptom severity was assessed again at a follow-up visit approximately 5-months after baseline. RESULTS: Hierarchical multiple regressions detected a significant interaction between inflammatory markers and emotional clarity on future depression severity, controlling for baseline depressive symptoms. Specifically, among adolescents with low levels of emotional clarity, higher levels of IL-6, CRP, and inflammatory composite scores were significantly associated with greater future depression severity. CONCLUSIONS: These results indicate that low emotional clarity and high inflammatory signaling may jointly confer risk for prospective depressive symptom severity among adolescents. Therapeutic interventions that improve emotional clarity may reduce risk of depressive symptoms among adolescents with low-grade peripheral inflammation.

Major stress in early childhood strengthens the association between peripheral inflammatory activity and corticostriatal responsivity to reward.

BACKGROUND: Severe, chronic stress during childhood accentuates vulnerability to mental and physical health problems across the lifespan. To explain this phenomenon, the neuroimmune network hypothesis proposes that childhood stressors amplify signaling between peripheral inflammatory cells and developing brain circuits that support processing of rewards and threats. Here, we conducted a preliminary test of the basic premises of this hypothesis. METHODS: 180 adolescents (mean age = 19.1 years; 68.9 % female) with diverse racial and ethnic identities (56.1 % White; 28.3 % Hispanic; 26.1 % Asian) participated. The Childhood Trauma Interview was administered to quantify early adversity. Five inflammatory biomarkers were assayed in antecubital blood - C-reactive protein, tumor necrosis factor-a, and interleukins-6, -8, and -10 - and were averaged to form a composite score. Participants also completed a functional MRI task to measure corticostriatal responsivity to the anticipation and acquisition of monetary rewards. RESULTS: Stress exposure and corticostriatal responsivity interacted statistically to predict the inflammation composite. Among participants who experienced major stressors in the first decade of life, higher inflammatory activity covaried with lower corticostriatal responsivity during acquisition of monetary rewards. This relationship was specific to participants who experienced major stress in early childhood, implying a sensitive period for exposure, and were evident in both the orbitofrontal cortex and the ventral striatum, suggesting the broad involvement of corticostriatal regions. The findings were independent of participants' age, sex, racial and ethnic identity, family income, and depressive symptoms. CONCLUSIONS: Collectively, the results are consistent with hypotheses suggesting that major stress in childhood alters brain-immune signaling.

Association between reward-related functional connectivity and tri-level mood and anxiety symptoms.

Depression and anxiety are associated with abnormalities in brain regions that process rewards including the medial orbitofrontal cortex (mOFC), the ventral striatum (VS), and the amygdala. However, there are inconsistencies in these findings. This may be due to past reliance on categorical diagnoses that, while valuable, provide less precision than may be required to understand subtle neural changes associated with symptoms of depression and anxiety. In contrast, the tri-level model defines symptom dimensions that are common (General Distress) or relatively specific (Anhedonia-Apprehension, Fears) to depression and anxiety related disorders, which provide increased precision. In the current study, eligibility was assessed by quasi-orthogonal screening questionnaires measuring reward and threat sensitivity (Behavioral Activation Scale; Eysenck Personality Questionnaire-Neuroticism). These participants were assessed on tri-level symptom severity and completed the Monetary Incentive Delay task during fMRI scanning. VS-mOFC and VS-amygdala connectivity were estimated during reward anticipation and reward outcome. Heightened General Distress was associated with lower VS-mOFC connectivity during reward anticipation (b = -0.064, p = 0.021) and reward outcome (b = -0.102, p = 0.014). Heightened Anhedonia-Apprehension was associated with greater VS-amygdala connectivity during reward anticipation (b = 0.065, p = 0.004). The present work has important implications for understanding the coupling between the mOFC and vS and the amygdala and the vS during reward processing in the pathophysiology of mood and anxiety symptoms and for developing targeted behavioral, pharmacological, and neuromodulatory interventions to help manage these symptoms.