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Black sheep get the blues: A psychobiological model of social rejection and depression
Open accessAbstract
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 (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
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“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
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“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
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“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
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“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
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“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]
In the citing paper
“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
In the citing paper
“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
In the citing paper
“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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Citations
Cites
The need to belong: Desire for interpersonal attachments as a fundamental human motivation.
Baumeister, R. F., & Leary, M. R. (1995) · Psychological Bulletin · doi:10.1037//0033-2909.117.3.497 · Cited by 23,245
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Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene
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Sapolsky, R. M. (2000) · Endocrine Reviews · doi:10.1210/er.21.1.55 · Cited by 7,533
From inflammation to sickness and depression: when the immune system subjugates the brain
Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2297 · Cited by 7,395
Effects of stress throughout the lifespan on the brain, behaviour and cognition
Lupien, S. J., McEwen, B. S., Gunnar, M. R., & Heim, C. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2639 · Cited by 6,256
Dickerson, S. S., & Kemeny, M. E. (2004) · Psychological Bulletin · doi:10.1037/0033-2909.130.3.355 · Cited by 5,881
Self-citationFreud, S. (1922) · The Journal of Nervous and Mental Disease · doi:10.1097/00005053-192211000-00066 · Cited by 5,444
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Sorted by citations
Slavich, G. M., & Irwin, M. R. (2014) · Psychological Bulletin · doi:10.1037/a0035302 · Cited by 2,206
Self-citationMarital quality and health: A meta-analytic review.
Robles, T. F., Slatcher, R. B., Trombello, J. M., & McGinn, M. M. (2013) · Psychological Bulletin · doi:10.1037/a0031859 · Cited by 1,764
So depression is an inflammatory disease, but where does the inflammation come from?
Berk, M., Williams, L. J., Jacka, F. N., O’Neil, A., Pasco, J. A., Moylan, S., Allen, N. B., Stuart, A. L., Hayley, A. C., Byrne, M. L., et al. (2013) · BMC Medicine · doi:10.1186/1741-7015-11-200 · Cited by 1,423
More than a feeling: A unified view of stress measurement for population science
Epel, E. S., Crosswell, A. D., Mayer, S. E., Prather, A. A., Slavich, G. M., Puterman, E., & Mendes, W. B. (2018) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2018.03.001 · Cited by 1,077
Self-citationEisenberger, N. I. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3231 · Cited by 1,016
Metadata
- 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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