Social neuroscience and health: neurophysiological mechanisms linking social ties with physical health


Although considerable research has shown the importance of social connection for physical health, little is known about the higher-level neurocognitive processes that link experiences of social connection or disconnection with health-relevant physiological responses. Here we review the key physiological systems implicated in the link between social ties and health and the neural mechanisms that may translate social experiences into downstream health-relevant physiological responses. Specifically, we suggest that threats to social connection may tap into the same neural and physiological 'alarm system' that responds to other critical survival threats, such as the threat or experience of physical harm. Similarly, experiences of social connection may tap into basic reward-related mechanisms that have inhibitory relationships with threat-related responding. Indeed, the neurocognitive correlates of social disconnection and connection may be important mediators for understanding the relationships between social ties and health.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Neural correlates of social disconnection and connection.
Figure 2: CNS regulation of inflammatory gene expression in immune cells.


  1. 1

    Holt-Lunstad, J., Smith, T.B. & Layton, J.B. Social relationships and mortality risk: a meta-analytic review. PLoS Med. 7, e1000316 (2010).

    Article  Google Scholar 

  2. 2

    Miller, G., Chen, E. & Cole, S.W. Health psychology: developing biologically plausible models linking the social world and physical health. Annu. Rev. Psychol. 60, 501–524 (2009).

    Article  Google Scholar 

  3. 3

    Irwin, M.R. & Cole, S.W. Reciprocal regulation of the neural and innate immune systems. Nat. Rev. Immunol. 11, 625–632 (2011).

    CAS  Article  Google Scholar 

  4. 4

    Finch, C.E. The Biology of Human Longevity: Inflammation, Nutrition and Aging in the Evolution of Life Spans (Academic Press, Boston, 2007).

  5. 5

    Meyer-Lindenberg, A. & Tost, H. Neural mechanisms of social risk for psychiatric disorders. (this volume)

  6. 6

    Cacioppo, J.T. & Hawkley, L.C. Perceived social isolation and cognition. Trends Cogn. Sci. 13, 447–454 (2009).

    Article  Google Scholar 

  7. 7

    Eisenberger, N.I., Lieberman, M.D. & Williams, K.D. Does rejection hurt: an fMRI study of social exclusion. Science 302, 290–292 (2003).

    CAS  Article  Google Scholar 

  8. 8

    Eisenberger, N.I. The pain of social disconnection: examining the shared neural underpinnings of physical and social pain. Nat. Rev. Neurosci. (in the press).

  9. 9

    Inagaki, T.K. & Eisenberger, N.I. Neural correlates of giving support to a loved one. Psychosom. Med. 74, 3–7 (2012).

    Article  Google Scholar 

  10. 10

    Delgado, M.R., Olsson, A. & Phelps, E.A. Extending animal models of fear conditioning to humans. Biol. Psychol. 73, 39–48 (2006).

    CAS  Article  Google Scholar 

  11. 11

    Bosch, J.A. et al. A general enhancement of autonomic and cortisol responses during social evaluative threat. Psychosom. Med. 71, 877–885 (2009).

    CAS  Article  Google Scholar 

  12. 12

    Dickerson, S.S. & Kemeny, M.E. Acute stressors and cortisol responses: a theoretical integration and synthesis of laboratory research. Psychol. Bull. 130, 355–391 (2004).

    Article  Google Scholar 

  13. 13

    Lundberg, U. & Frankenhaeuser, M. Pituitary-adrenal and sympathetic-adrenal correlates of distress and effort. J. Psychosom. Res. 24, 125–130 (1980).

    CAS  Article  Google Scholar 

  14. 14

    Cole, S.W. et al. Social regulation of gene expression in human leukocytes. Genome Biol. 8, R189 (2007).

    Article  Google Scholar 

  15. 15

    Miller, G.E. et al. A genomic fingerprint of chronic stress in humans: blunted glucocorticoid and increased NF-kappaB signaling. Biol. Psychiatry 64, 266–272 (2008).

    CAS  Article  Google Scholar 

  16. 16

    Sloan, E.K. et al. Social stress enhances sympathetic innervation of primate lymph nodes: mechanisms and implications for viral pathogenesis. J. Neurosci. 27, 8857–8865 (2007).

    CAS  Article  Google Scholar 

  17. 17

    Mobbs, D. et al. From threat to fear: the neural organization of defensive fear systems in humans. J. Neurosci. 29, 12236–12243 (2009).

    CAS  Article  Google Scholar 

  18. 18

    Mobbs, D. et al. Neural activity associated with monitoring the oscillating threat value of a tarantula. Proc. Natl. Acad. Sci. USA 107, 20582–20586 (2010).

    CAS  Article  Google Scholar 

  19. 19

    Phelps, E.A., Delgado, M.R., Nearing, K.I. & LeDoux, J.E. Extinction learning in humans: role of the amygdala and vmPFC. Neuron 43, 897–905 (2004).

    CAS  Article  Google Scholar 

  20. 20

    Milad, M.R. et al. A role for the human dorsal anterior cingulate cortex in fear expression. Biol. Psychiatry 62, 1191–1194 (2007).

    Article  Google Scholar 

  21. 21

    Burgos-Robles, A., Vidal-Gonzalez, I. & Quirk, G.J. Sustained conditioned responses in prelimbic prefrontal neurons are correlated with fear expression and extinction failure. J. Neurosci. 29, 8474–8482 (2009).

    CAS  Article  Google Scholar 

  22. 22

    Critchley, H.D. et al. Human cingulate cortex and autonomic control: converging neuroimaging and clinical evidence. Brain 126, 2139–2152 (2003).

    Article  Google Scholar 

  23. 23

    Bandler, R., Keay, K.A., Floyd, N. & Price, J. Central circuits patterned autonomic activity during active versus passive emotional coping. Brain Res. Bull. 53, 95–104 (2000).

    CAS  Article  Google Scholar 

  24. 24

    Critchley, H.D. Neural mechanisms of autonomic, affective and cognitive integration. J. Comp. Neurol. 493, 154–166 (2005).

    Article  Google Scholar 

  25. 25

    Kross, E., Berman, M.G., Mischel, W., Smith, E.E. & Wager, T.D. Social rejection shares somatosensory representations with physical pain. Proc. Natl. Acad. Sci. USA 108, 6270–6275 (2011).

    CAS  Article  Google Scholar 

  26. 26

    Eisenberger, N.I., Inagaki, T.K., Muscatell, K.A., Haltom, K.E.B. & Leary, M.R. The neural sociometer: brain mechanisms underlying state self-esteem. J. Cogn. Neurosci. 23, 3448–3455 (2011).

    Article  Google Scholar 

  27. 27

    O'Connor, M.F. et al. Craving love? Enduing grief activates brain's reward center. Neuroimage 42, 969–972 (2008).

    Article  Google Scholar 

  28. 28

    Panksepp, J. Affective Neuroscience: The Foundations of Human and Animal Emotions (Oxford Univ. Press, New York, 1998).

  29. 29

    Critchley, H.D., Corfield, D.R., Chandler, M.P., Mathias, C.J. & Dolan, R.J. Cerebral correlates of autonomic cardiovascular arousal: a functional neuroimaging investigation in humans. J. Physiol. (Lond.) 523, 259–270 (2000).

    CAS  Article  Google Scholar 

  30. 30

    Gianaros, P.J., van der Veen, F.M. & Jennings, J.R. Regional cerebral blood flow correlates with heart period and high-frequency heart period variability during working-memory tasks: implications for the cortical and subcortical regulation of cardiac autonomic activity. Psychophysiology 41, 521–530 (2004).

    Article  Google Scholar 

  31. 31

    Wager, T.D. et al. Brain mediators of cardiovascular responses to social threat. Part II. Prefrontal-subcortical pathways and relationship with anxiety. Neuroimage 47, 836–851 (2009).

    Article  Google Scholar 

  32. 32

    Wang, J. et al. Perfusion functional MRI reveals cerebral blood flow pattern under psychological stress. Proc. Natl. Acad. Sci. USA 102, 17804–17809 (2005).

    CAS  Article  Google Scholar 

  33. 33

    Eisenberger, N.I., Taylor, S.E., Gable, S.L., Hilmert, C.J. & Lieberman, M.D. Neural pathways link social support to attenuated neuroendocrine stress responses. Neuroimage 35, 1601–1612 (2007).

    Article  Google Scholar 

  34. 34

    Slavich, G.M., Way, B.M., Eisenberger, N.I. & Taylor, S.E. Neural sensitivity to social rejection is associated with inflammatory responses to social stress. Proc. Natl. Acad. Sci. USA 107, 14817–14822 (2010).

    CAS  Article  Google Scholar 

  35. 35

    Henke, P.G. The telencephalic limbic system and experimental gastric pathology: a review. Neurosci. Biobehav. Rev. 6, 381–390 (1982).

    CAS  Article  Google Scholar 

  36. 36

    Milad, M.R. & Quirk, G.J. Neurons in medial prefrontal cortex signal memory for fear extinction. Nature 420, 70–74 (2002).

    CAS  Article  Google Scholar 

  37. 37

    Atlas, L.Y., Bolger, N., Linquist, M.A. & Wager, T.D. Brain mediators of predictive cue effects on perceived pain. J. Neurosci. 30, 12964–12977 (2010).

    CAS  Article  Google Scholar 

  38. 38

    Pruessner, J.C. et al. Deactivation of the limbic system during acute psychosocial stress: evidence from positron emission tomography and functional magnetic resonance imaging. Biol. Psychiatry 63, 234–240 (2008).

    Article  Google Scholar 

  39. 39

    Thayer, J.F., Ahs, F., Fredrikson, M., Sollers, J.J. III & Wager, T.D. A meta-analysis of heart rate variability and neuroimaging studies: implications for heart rate variability as a marker of stress and health. Neurosci. Biobehav. Rev. 36, 747–756 (2012).

    Article  Google Scholar 

  40. 40

    Buchanan, T.W. et al. Medial prefrontal cortex damage affects physiological and psychological stress responses differently in men and women. Psychoneuroendocrinology 35, 56–66 (2010).

    Article  Google Scholar 

  41. 41

    Eisenberger, N.I. et al. Attachment figures activate a safety signal-related neural region and reduce pain experience. Proc. Natl. Acad. Sci. USA 108, 11721–11726 (2011).

    CAS  Article  Google Scholar 

  42. 42

    Onoda, K. et al. Decreased ventral anterior cingulate cortex activity is associated with reduced social pain during emotional support. Soc. Neurosci. 4, 443–454 (2009).

    Article  Google Scholar 

  43. 43

    Piferi, R.L. & Lawler, K.A. Social support and ambulatory blood pressure: an examination of both receiving and giving. Int. J. Psychophysiol. 62, 328–336 (2006).

    Article  Google Scholar 

  44. 44

    Brown, S.L., Nesse, R.M., Vinokur, A.D. & Smith, D.M. Providing social support may be more beneficial than receiving it: results from a prospective study of mortality. Psychol. Sci. 14, 320–327 (2003).

    Article  Google Scholar 

  45. 45

    Thomas, E. Forebrain mechanisms in the relief of fear: the role of the lateral septum. Psychobiol. 16, 36–44 (1991).

    Google Scholar 

  46. 46

    Uvnäs-Moberg, K. Oxytocin may mediate the benefits of positive social interaction and emotions. Psychoneuroendocrinology 23, 819–835 (1998).

    Article  Google Scholar 

  47. 47

    Zubieta, J.K. et al. Regional mu opioid receptor regulation of sensory and affective dimensions of pain. Science 293, 311–315 (2001).

    CAS  Article  Google Scholar 

  48. 48

    Insel, T.R. & Shapiro, L.E. Oxytocin receptor distribution reflects social organization in monogamous and polygamous voles. Proc. Natl. Acad. Sci. USA 89, 5981–5985 (1992).

    CAS  Article  Google Scholar 

  49. 49

    Drolet, G. et al. Role of endogenous opioid system in the regulation of the stress response. Prog. Neuropsychopharmacol. Biol. Psychiatry 25, 729–741 (2001).

    CAS  Article  Google Scholar 

  50. 50

    Bonnet, M.-P., Beloeil, H., Benhamou, D., Mazoit, J.-X. & Asehnoune, K. The mu-opioid receptor mediates morphine-induced tumor necrosis factor and interleukin-6 inhibition in toll-like receptor 2–stimulated monocytes. Anesth. Analg. 106, 1142–1149 (2008).

    CAS  Article  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Naomi I Eisenberger.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Eisenberger, N., Cole, S. Social neuroscience and health: neurophysiological mechanisms linking social ties with physical health. Nat Neurosci 15, 669–674 (2012).

Download citation

Further reading


Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing