Black sheep get the blues: a psychobiological model of social rejection and depression
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Major life events involving social rejection are strongly associated with onset of depression. To account for this relation, we propose a psychobiological model in which rejection-related stressors elicit a distinct and integrated set of cognitive, emotional, and biological changes that may evoke depression. In this model, social rejection events activate brain regions involved in processing negative affect and rejection-related distress (e.g., anterior insula, dorsal anterior cingulate cortex). They also elicit negative self-referential cognitions (e.g., "I'm undesirable," "Other people don't like me") and related self-conscious emotions (e.g., shame, humiliation). Downstream biological consequences include upregulation of the hypothalamic-pituitary-adrenal axis, sympathetic-adrenal-medullary axis, and inflammatory response. Pro-inflammatory cytokines play an important role in this process because they induce a constellation of depressotypic behaviors called sickness behaviors. Although these changes can be short-lived, sustained inflammation may occur via glucocorticoid resistance, catecholamines, sympathetic innervation of immune organs, and immune cell aging. This response also may be moderated by several factors, including prior life stress, prior depression, and genes implicated in stress reactivity.
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Adverse social experiences characterized by loss or threat activate proinflammatory cytokine activity and trigger alterations in genes regulating proinflammatory cytokine production.
“adverse social experiences characterized by loss or threat activate proinflammatory cytokine activity (Giletta et al. 2018, Slavich & Cole 2013) and trigger alterations in the genes regulating proinflammatory cytokine production (Slavich et al. 2010)”
From Adolescent Suicide as a Failure of Acute Stress-Response Systems. (2019) · cites this paper as Slavich et al. 2010
A primacy for interpersonal loss and social rejection life events in predicting depression emerges even when interpersonal loss events are compared to other stressors of the same severity level.
“a primacy for interpersonal loss and social rejection life events in predicting depression emerges even when interpersonal loss events are compared to other stressors of the same severity level”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Slavich, O'Donovan, et al., 2010
Major life events involving interpersonal loss or social rejection are particularly strongly related to MDD.
“a substantial body of evidence now exists showing that major life events involving interpersonal loss or social rejection are particularly strongly related to MDD”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Slavich, O'Donovan, et al., 2010
Social stress-related reductions in glucocorticoid sensitivity may be one mechanism linking social threat and rejection with elevated inflammation and risk for depression.
“social stress-related reductions in glucocorticoid sensitivity may be one mechanism linking social threat and rejection with elevated inflammation and risk for depression”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Slavich, O'Donovan, et al., 2010
The social signal transduction theory specifies that situations involving social threat are represented neurally by brain regions such as the anterior insula and dACC, which process experiences of negative affect and rejection-related distress.
“this theory specifies that situations involving social threat are represented neurally by brain regions such as the anterior insula and dACC, which process experiences of negative affect and rejection-related distress”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Slavich, O'Donovan, et al., 2010
Stress triggers the release of pro-inflammatory cytokines, which access the central nervous system, eliciting neurobehavioral adjustments that manifest as depressive symptoms.
“Most center around the notion that stress triggers the release of pro-inflammatory cytokines, which access the central nervous system, eliciting neurobehavioral adjustments that manifest as depressive symptoms (3–5).”
From Clustering of depression and inflammation in adolescents previously exposed to childhood adversity (2012) · cites this paper as [5]
Social rejection is one of the strongest proximal risk factors for depression.
“Social rejection is one of the strongest proximal risk factors for depression (Slavich et al., 2010)”
From Social functioning in major depressive disorder (2016) · cites this paper as Slavich et al., 2010
A polymorphism in the MOR gene influences neural and psychological responses to rejection, likely by affecting opioid receptor expression and signalling efficiency.
“Recently, a polymorphism in the MOR gene has been found to influence neural and psychological responses to rejection, likely by affecting opioid receptor expression and signalling efficiency (Slavich et al., 2010).”
From Social functioning in major depressive disorder (2016) · cites this paper as Slavich et al., 2010
Insufficient validation may trigger negative affect and negative self-relevant cognitions, which are known risk factors for depression.
“Insufficient validation may then trigger consequences of this need threat, such as negative affect (e.g., feeling distressed, sad, anxious, or embarrassed), and negative self-relevant cognitions (viewing oneself as less worthy, or less likable), which are known risk factors for depression (Hankin & Abramson, 2001; Masten et al., 2011; Slavich, O’Donovan, Epel, & Kemeny, 2010).”
From Getting Fewer “Likes” Than Others on Social Media Elicits Emotional Distress Among Victimized Adolescents (2020) · cites this paper as Slavich, O’Donovan, Epel, & Kemeny, 2010
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Slavich, G. M., & Cole, S. W. (2013) · Clinical Psychological Science · doi:10.1177/2167702613478594 · Cited by 523 · see citing works
Self-citationThe neurobiology of depression and antidepressant action
Willner, P., Scheel-Krüger, J., & Belzung, C. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2012.12.007 · Cited by 519 · see citing works
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“…impact on stress research, as most articles published over the past century subsequently conceptualized life stress as a single, unitary construct, with little attention paid to how different stressors might have varying consequences for health (Hammen 2005, Monroe 2008, Slavich et al. 2010a).”
BackgroundInfluentialSelf-citationRisk factors for depression: an autobiographical review
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Neural sensitivity to social rejection is associated with inflammatory responses to social stress
Slavich, G. M., Way, B. M., Eisenberger, N. I., & Taylor, S. E. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1009164107 · Cited by 418 · see citing works
Self-citationDiamond, L. M., & Alley, J. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104720 · Cited by 412 · see citing works
Slavich, G. M., & Sacher, J. (2019) · Psychopharmacology · doi:10.1007/s00213-019-05326-9 · Cited by 383 · see citing works
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Navigating the Social Environment in Adolescence: The Role of Social Brain Development
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Clustering of depression and inflammation in adolescents previously exposed to childhood adversity
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Life Stress and Health: A Review of Conceptual Issues and Recent Findings
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Self-citationStress and Type 2 Diabetes: A Review of How Stress Contributes to the Development of Type 2 Diabetes
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Self-citationAssociation of Higher Cortical Amyloid Burden With Loneliness in Cognitively Normal Older Adults
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Self-citationRaphe GABAergic Neurons Mediate the Acquisition of Avoidance after Social Defeat
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Self-citationTargeted Rejection Predicts Hastened Onset of Major Depression
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Self-citationPeer Relations and Developmental Psychopathology
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“First, research is necessary to understand which specific types of life stress most strongly trigger inflammation and lead to the development of a proinflammatory phenotype (Epel et al., 2018; Irwin and Slavich, 2017; Slavich et al., 2010).”
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Inflammation, Self-Regulation, and Health: An Immunologic Model of Self-Regulatory Failure
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The Research on Risk Factors for Adolescents’ Mental Health
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Self-citationCross-sectional study of depression and help-seeking in Uttarakhand, North India
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Self-citationA social neuroscience perspective on stress and health.
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Self-citationEmbodiment of cognition and emotion.
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- Authors
- Slavich, G. M., O’Donovan, A., Epel, E. S., & Kemeny, M. E.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Slavich, George M.
- Venue
- Neuroscience & Biobehavioral Reviews
- Publisher
- Elsevier BV
- Published
- 2010-09
- Volume
- 35
- Issue
- 1
- Pages
- 39-45
- ISSN
- 0149-7634 (ISSN-L)
- PMC
- PMC2926175
- OpenAlex
- W2089060681
- Cited by
- 362
- References
- 89
- Citations by year
- 2026: 15 · 2025: 16 · 2024: 37 · 2023: 30 · 2022: 35 · 2021: 28 · 2020: 34 · 2019: 18 · 2018: 20 · 2017: 22 · 2016: 27 · 2015: 18 · 2014: 13 · 2013: 16 · 2012: 20
- FWCI
- 1.35
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuroscience & Biobehavioral Reviews (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Mental Health (T32MH019391)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Social Sciences › Psychology › Social Psychology › Death Anxiety and Social Exclusion
- Keywords
- social rejection, depression, psychobiological model, self-conscious emotions, shame, anterior insula, dorsal anterior cingulate cortex, hypothalamic-pituitary-adrenal axis, sympathoadrenal system, inflammatory cytokines, sickness behavior, glucocorticoid resistance, immunosenescence
- MeSH terms
- Animals, Depression, Humans, Rejection, Psychology, Stress, Psychological
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