Interpersonal life stress, inflammation, and depression in adolescence: Testing Social Signal Transduction Theory of Depression

Abstract

Background: Depression rates increase markedly for girls across the adolescent transition, but the social-environmental and biological processes underlying this phenomenon remain unclear. To address this issue, we tested a key hypothesis from Social Signal Transduction Theory of Depression, which posits that individuals who mount stronger inflammatory responses to social stress should exhibit greater increases in depressive symptoms following interpersonal life stress exposure than those who mount weaker inflammatory responses to such stress.

Method: Participants were 116 adolescent girls (M_age = 14.71) at risk for psychopathology, defined as having a history of mental health concerns (e.g., psychiatric treatment, significant symptoms) over the past 2 years. At baseline, we characterized their inflammatory reactivity to social stress by quantifying their salivary proinflammatory cytokine responses to a laboratory-based social stressor. Then, 9 months later, we assessed the interpersonal and noninterpersonal stressful life events that they experienced over the prior 9 months using an interview-based measure of life stress.

Results: As hypothesized, greater interpersonal life stress exposure was associated with significant increases in depression over time, but only for girls exhibiting stronger salivary tumor necrosis factor-α and interleukin-1β reactivity to social stress. In contrast, noninterpersonal stress exposure was unrelated to changes in depression longitudinally, both alone and when combined with youths' cytokine reactivity scores.

Discussion: These results are consistent with Social Signal Transduction Theory of Depression and suggest that heightened inflammatory reactivity to social stress may increase adolescents' risk for depression. Consequently, it may be possible to reduce depression risk by modifying inflammatory responses to social stress.

Keywords: cytokines; development; disease; inflammation; major depressive disorder; risk; social stress; vulnerability.

Figure 1.. Interpersonal life stress exposure, inflammation, and depressive symptoms.

Hierarchical linear regression models revealed that recent interpersonal life stress exposure interacted with youths’ social-stress induced salivary cytokine reactivity to predict significant increases in depressive symptoms over nine months, while controlling for age, ethnicity, and pubertal status. Results for TNF-α are shown in panel (A), where greater interpersonal life stress exposure predicted significant increases in depressive symptoms over time for girls exhibiting high TNF-α reactivity to social stress (simple slopes [SE], 0.019 [0.003], p < .001) but not for girls exhibiting low TNF-α reactivity to social stress (simple slopes [SE], 0.01 [0.003], p = 0.08). As shown in panel (B), similar effects were found for IL-1β, where greater interpersonal life stress exposure predicted significant increases in depressive symptoms over time for girls exhibiting high IL-1β reactivity to social stress (simple slopes [SE], 0.017 [0.003], p < .001) but not for girls exhibiting low IL-1β reactivity to social stress (simple slopes [SE], 0.01 [0.002], p = 0.101). In contrast to these results, non-interpersonal stress exposure was not related to changes in depressive symptoms longitudinally, either alone or in combination with participants’ salivary cytokine reactivity scores. Dot sizes represent the magnitude of participants’ cytokine reactivity to the social stress task, with larger dots indicating greater reactivity.