From Stress to Inflammation and Major Depressive Disorder: A Social Signal Transduction Theory of Depression

Psychological Bulletin (Impact Factor: 14.76). 01/2014; 140(3). DOI: 10.1037/a0035302
Source: PubMed


Major life stressors, especially those involving interpersonal stress and social rejection, are among the strongest proximal risk factors for depression. In this review, we propose a biologically plausible, multilevel theory that describes neural, physiologic, molecular, and genomic mechanisms that link experiences of social-environmental stress with internal biological processes that drive depression pathogenesis. Central to this social signal transduction theory of depression is the hypothesis that experiences of social threat and adversity up-regulate components of the immune system involved in inflammation. The key mediators of this response, called proinflammatory cytokines, can in turn elicit profound changes in behavior, which include the initiation of depressive symptoms such as sad mood, anhedonia, fatigue, psychomotor retardation, and social-behavioral withdrawal. This highly conserved biological response to adversity is critical for survival during times of actual physical threat or injury. However, this response can also be activated by modern-day social, symbolic, or imagined threats, leading to an increasingly proinflammatory phenotype that may be a key phenomenon driving depression pathogenesis and recurrence, as well as the overlap of depression with several somatic conditions including asthma, rheumatoid arthritis, chronic pain, metabolic syndrome, cardiovascular disease, obesity, and neurodegeneration. Insights from this theory may thus shed light on several important questions including how depression develops, why it frequently recurs, why it is strongly predicted by early life stress, and why it often co-occurs with symptoms of anxiety and with certain physical disease conditions. This work may also suggest new opportunities for preventing and treating depression by targeting inflammation. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

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    • "Recovery (i.e., a process of psychophysiological unwinding through which the activation associated with the experience of stressor at work is restored to its baseline level) may play a central role in the transition from acute, short-lived physiological reactions associated with the exposure to job stressors to chronic physiological activation (Geurts & Sonnentag, 2006). According to some authors, the association between stressors and biomarkers of stress related to inflammation seems to be stronger for stressors which involve social conflict, rejection, or exclusion, such as interpersonal conflict at work (Slavich & Irwin, 2014). ICW is a form of social stressor that refers to negative interactions with others in the workplace. "
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    ABSTRACT: This study examined the association between interpersonal conflict at work (ICW) and serum levels of three possible biomarkers of stress, namely the pro-inflammatory cytokines Interleukin 1 beta (IL-1β), Interleukin 12 (IL-12), and Interleukin 17 (IL-17). Additionally, this study investigated the role of negative affectivity (NA) in the relationship between ICW and the pro-inflammatory cytokines. Data from 121 employees in an Italian healthcare organization were analyzed using structural equation modeling. Results showed that ICW was positively associated with IL-1β, IL-12, and IL-17, after controlling for the effect of gender. Moreover, ICW completely mediated the relationship between NA and the pro-inflammatory cytokines IL-1β, IL-12, and IL-17. This mediating effect was significant after controlling for the effect of gender. Overall, this study suggests that work-related stress may be associated with biomarkers of inflammation, and that negative affectivity may influence the stress process affecting the exposure to psychosocial stressors.
    Journal of Behavioral Medicine 07/2015; DOI:10.1007/s10865-015-9658-x · 3.10 Impact Factor
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    • "To the extent that frequent activation of the immune system contributes to physiological dysregulation (Brydon & Steptoe, 2005; Steptoe et al., 2007), repeated episodes of emotion-induced inflammatory activity may be predictive of future health outcomes. Indeed, over time, physiological dysregulation driven by inflammatory activity leads to or is associated with the onset or worsening of many mental disorders, such as schizophrenia (Müller & Schwarz, 2005), depression (Slavich & Irwin, 2014), and bipolar disorder (Goldstein, Kemp, Soczynska, McIntyre, 2009), and of many physical illnesses, such as autoimmune disorders (Stojanovich & Marisavljevich, 2008), cancer (Reuter, Gupta, Chaturvedi, & Aggarwal, 2010), and Alzheimer's disease (Rubio-Perez & Morillas-Ruiz, 2012). Importantly, because many of these health outcomes may be brought about or exacerbated by a tendency to experience avoidance-oriented emotions and motivational states (O'Donovan, Slavich, Epel, & Neylan, 2013), psychological assessments of how people regularly respond to stressors may be predictive of health outcomes. "
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    ABSTRACT: Psychological stressors reliably trigger systemic inflammatory activity as indexed by levels of proinflammatory cytokines. This experiment demonstrates that one's specific emotional reaction to a stressor may be a significant determinant of whether an inflammatory reaction occurs in response to that stressor. Based on extant correlational evidence and theory, a causal approach was used to determine whether an avoidant emotion (anxiety) triggers more inflammatory activity than an approach emotion (anger). In an experimental design (N = 40), a 3-way Emotion Condition × Time × Analyte interaction revealed that a writing-based anxiety induction, but not a writing-based anger induction, increased mean levels of interferon-γ (IFN- γ) and interleukin-1β (IL-1β), but not interleukin-6 (IL-6) in oral mucous, F(2, 54) = 4.64, p = .01, ηp2 = .15. Further, self-reported state anxiety predicted elevated levels of proinflammatory cytokines, all ΔR2 >.06, ps <.04, but self-reported state anger did not. These results constitute the first evidence to our knowledge that specific negative emotions can differentially cause inflammatory activity and support a theoretical model explaining these effects based on the avoidance or approach motivations associated with emotions. (PsycINFO Database Record (c) 2015 APA, all rights reserved).
    Emotion 06/2015; 15(4). DOI:10.1037/emo0000055 · 3.88 Impact Factor
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    • "First, we calculated effect sizes for each inflammatory marker in suicidal patients compared to non-suicidal patients on the one hand and compared to healthy subjects on the other hand. Then, in view of the clinical perspective, we made a distinction (Slavich and Irwin, 2014) between the levels of pro-inflammatory cytokines (IL1, IL2, IL6, IL8, TNFalpha, IFNgamma) and anti-inflammatory cytokines (IL4, IL10, TGFbeta1). "
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    ABSTRACT: We conducted the first meta-analysis of studies comparing the plasma and CSF concentrations of cytokines in suicidal patients vs. non-suicidal patients or healthy controls. We searched Medline, Web of Science, and PsycINFO from 1965 to November 2014 for relevant studies. Manual searches of references and unpublished data were also included. Suicidal patients included severe suicide ideators and suicide attempters. Eleven articles were available for the meta-analysis, for a total sample size of 494 suicidal patients, 497 non-suicidal patients and 398 healthy controls. Levels of 6 independent plasma cytokines (IL2, IL6, TNFalpha, IFNgamma, IL4, TGFbeta) were meta-analyzed for plasma studies comparing suicidal vs. both controls. IL8 level was meta-analyzed for cerebrospinal fluid studies comparing suicidal patients with healthy controls. We reported with medium effect size, that suicidal patients had: 1) lower IL2 plasma levels than both non-suicidal patients and healthy controls (medium effect size); 2) lower IL4 and higher TGFbeta plasma levels than healthy controls. Our results promote the hypothesis of altered inflammatory markers in suicidal patients, for both pro-inflammatory (IL2) and anti-inflammatory (IL4 and TGFbeta) cytokines. Copyright © 2015. Published by Elsevier Inc.
    Brain Behavior and Immunity 02/2015; 46. DOI:10.1016/j.bbi.2015.02.004 · 5.89 Impact Factor
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