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

By George M. Slavich, Michael R. Irwin. Psychological bulletin, 2014

1,994 citations recorded by the source corpus.

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.

Subfields: Behavioral Neuroscience, Biological Psychiatry, Social Psychology

View Paper: https://www.semanticscholar.org/paper/5082f6dd27c1d0dc876ce36a16b575a8efc30b58

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Citations in the corpus

Inflammation: depression fans the flames and feasts on the heat. (2015, background): “, nuclear factor-kB, NF-kB) disrupt glucocorticoid receptor function and expression, leading to unrestrained inflammatory responses that could further fuel depressive symptoms (2, 26, 28).”
Why Sleep Is Important for Health: A Psychoneuroimmunology Perspective (2014, background): “Such a conserved transcriptional response to adversity, of which sleep disturbance is one type, has been extensively discussed in prior reviews (Irwin & Cole 2011, Slavich & Irwin 2014).”
The psychology of the COVID-19 pandemic: A group-level perspective. (2020, background): “During stress, the sympathetic nervous system suppresses antiviral processes and up-regulates proinflammatory processes via the neurotransmitter norepinephrine (Slavich & Irwin, 2014).”
A Unified Model of Depression (2016, positive): “Finally, in line with other evidence for a parallel between physical and emotional pain (e.g., Eisenberger & Lieberman, 2004), genes that regulate endogenous opioid production have been found to moderate depressive reactions to targeted rejection (Slavich & Irwin, 2014).”
Why Social Relationships Are Important for Physical Health: A Systems Approach to Understanding and Modifying Risk and Protection (2018, background): “Social conditions such as rejection and interpersonal stress can also increase the risk of depression, suggesting that the associations between social conditions and health are complex and may share common mechanisms (Slavich & Irwin 2014).”
Belonging: a review of conceptual issues, an integrative framework, and directions for future research (2021, background): “…the biological processes that are affected by experiences of disconnection versus belonging, which can help researchers elucidate the regulatory logic of these systems to understand better what aspects of belonging are most critical or essential for health (Slavich, 2020; Slavich & Irwin, 2014).”
Sleep Disturbance, Sleep Duration, and Inflammation: A Systematic Review and Meta-Analysis of Cohort Studies and Experimental Sleep Deprivation (2015, background): “Sleep influences two primary effector systems, the hypothalamus-pituitary-adrenal axis and the sympathetic nervous system, which together shift the basal gene expression profile toward increased proinflammatory skewing (14,123).”
Stress and depression: old questions, new approaches (2015, background): “Recent research also increasingly links HPA stress responses to immunological processes that may promote depression [14,42].”
Early-Life Adversity and Physical and Emotional Health across the Lifespan: A Neuro-Immune Network Hypothesis (2015, background): “However, growing evidence suggests both are components of an integrated, bidirectional, network that detects threats to wellbeing and mobilizes behavioral, physiologic, and inflammatory resources for coping (11,59,60).”
The Lancet Commission on global mental health and sustainable development. (2018, background): “120 The immune system is a biological area of emerging interest in mental health, and several studies have reported that a subgroup of people with mental disorders (eg, depression and psychosis) have altered inflammatory biomarkers.”