Proinflammatory Cytokine Reactivity to Social Stress: A Prospective Risk Factor for Adolescent Suicide

• In Event: Stress and Stress Responses: Social, Cultural, and Biological Links to Adolescent Suicidality

Abstract

Current psychological theories (Miller, Chen, & Parker, 2011; Slavich & Cole, 2013) implicate the role of biological stress responses in the development of chronic disease and psychopathology across the lifespan. Remarkably, associations between these biological responses and suicidal thoughts and behaviors (STB) rarely have been examined. Acute inflammatory responses to stress may be especially relevant as they are part of an innate immune response to adversity, which if engaged chronically, may confer increased risk for deleterious physical and psychological outcomes (Dowlati et al., 2010; Munkholm et al., 2013; MacDowell et al., 2013), including suicide (Gabbay et al., 2009; Mina et al., 2014). To examine this possibility, we investigated how social stress-induced changes in pro-inflammatory cytokines, signaling proteins that mediate key stages of the aforementioned immune response cascade (Dantzer et al., 2008), are associated with the development of suicidal behavior in adolescence. Notably, as compared to prior research (REF), this study is unique insofar as it examined cytokine responses to in vivo stress (i.e., cytokine reactivity) – rather than basal cytokine levels – to better understand biological stress processes that may be relevant for STB. Specifically, we hypothesized that reactive proinflammatory cytokine dysregulation (i.e., post vs pre social stress) would predict suicidal behavior across a 9-month follow-up period, after controlling for baseline suicidal behaviors.

This study longitudinally assessed these associations in a sample of adolescent females (N = 157; aged 12 to 16 years old) at elevated risk for psychopathology given clinically elevated psychological symptoms over the prior two years. We used the Trier Social Stress Test (TSST) to experientially induce a brief experience of acute social stress and assessed participants’ proinflammatory cytokine levels before and after this stressor, enabling us to quantify participants’ inflammatory reactivity to acute social stress. Prior history of suicidal behavior was assessed at baseline and 9-month follow-up using a structured clinical interview. Preliminary findings revealed that blunted reactivity of pro-inflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) individually and collectively (as represented by a latent factor) predicted subsequent suicidal behavior over the follow-up period. Findings remain consistent even after controlling for prior suicidal thoughts and behaviors, respectively. This study thus highlights the potential role of social stress-induced cytokine reactivity in predicting which adolescents are at higher risk for engaging in suicidal behaviors over time. The study benefited from a number of strengths: the measurement of proinflammatory cytokines in the context of a socially themed stressor, the availability of longitudinal data over a 9-month period, and the use of an adolescent sample at risk for suicidal behaviors. Implications for further research and related developmental outcomes will be discussed.

Authors

• Matthew Graham Clayton, University of North Carolina at Chapel Hill
  Presenting Author

• Matteo Giletta, Ghent University
  Non-Presenting Author

• Paul David Hastings, University of California - Davis
  Non-Presenting Author

• Matthew K. Nock, Harvard University
  Non-Presenting Author

• Karen Rudolph, University of Illinois at Urbana-Champaign
  Non-Presenting Author

• George M Slavich, University of California, Los Angeles
  Non-Presenting Author

• Mitchell J Prinstein, University of North Carolina at Chapel Hill
  Non-Presenting Author