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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]
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“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
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“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
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“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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Robles, T. F., & Kane, H. S. (2012) · Oxford University Press eBooks · doi:10.1093/oxfordhb/9780195394399.013.0011 · Cited by 1
Martínez, R. F., Fernández-Pereira, C., Pérez-Rodríguez, D., Salgado‐Barreira, Á., Veiga, C., Teso-Cuesta, S., Prieto-González, J. M., Diez, J. M., & Agís‐Balboa, R. C. (2022) · International Journal of Translational Medicine · doi:10.3390/ijtm3010002 · Cited by 4
Belief Systems and Ideologies as Psychological Need Reconciliation
Müller, V., & Gries, T. (2024) · Oxford University Press eBooks · doi:10.1093/oso/9780197670187.003.0006 · Cited by 1
Brietzke, S. C., Barbarossa, K., & Meyer, M. L. (2024) · Cerebral Cortex · doi:10.1093/cercor/bhae280 · Cited by 1
Strickland, M. G., Myszkowski, N., Hooker, E. D., Zoccola, P. M., & Dickerson, S. S. (2024) · Psychosomatic Medicine · doi:10.1097/psy.0000000000001336 · Cited by 2
Knauft, K. M., Davis, K. M., Jiang, Y., Shields, G. S., Joseph, N. T., Slavich, G. M., & Zilioli, S. (2025) · Developmental Psychobiology · doi:10.1002/dev.70034 · Cited by 1
Self-citationRider, M. (2017) · EXPLORE · doi:10.1016/j.explore.2017.04.020 · Cited by 1
Influence of Negative Life Events on Depression Among In-School Adolescents In Southwest Nigeria
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Who cares?:negative peer experiences and empathy for rejected others
Gibson, C. J. (2018) · Cited by 1
Zhang, J., Hu, Z., Zheng, S., & Liu, Y. (2023) · Research Square · doi:10.21203/rs.3.rs-2632789/v1 · Cited by 1
von Guttenberg, M., Gassen, J., & Slavich, G. M. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.06.18.660364 · Cited by 2
Self-citation
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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