César Venero
Angela J. Grippo
Julian C. L. Lai- 1Department of Psychobiology, Universidad Nacional de Educación a Distancia (UNED), Madrid, Spain
- 2Department of Psychology, Northern Illinois University, DeKalb, IL, United States
- 3Psychophysiology Laboratory, Department of Social and Behavioural Sciences, City University of Hong Kong, Kowloon, Hong Kong SAR, China
Editorial on the Research Topic
Endocrinology of loneliness and social isolation
Recent research has identified loneliness or perceived social isolation (PSI) as one of the most crucial factors contributing to ill health and mortality (Rico-Uribe et al., 2018; Wang et al., 2018). Loneliness is conceptually different from social isolation, which is an objective measure of the lack of social relationships and interactions (Cacioppo et al., 2014). Loneliness relates to the quality rather than the quantity of social relationships, and thus individuals can be socially content when alone or be lonely in a crowd. Due to the rising prevalence of loneliness, researchers have called for immediate public health attention to address this “behavioral epidemic” (Jeste et al., 2020). The urgency of this issue has triggered a proliferation of studies aimed at addressing the physiological mechanisms translating loneliness into ill health or increased mortality in the last decades (reviewed by Cacioppo et al., 2015; Brown et al., 2018; Campagne, 2019; Smith et al., 2020). It has been suggested that dysregulation in the functioning of the neuroendocrine-immune axis is a central feature of the pathophysiology of loneliness (e.g., Hawkley and Cacioppo, 2003), despite ambiguous findings concerning the effect of social isolation on HPA and immune functioning (Hawkley et al., 2012). According to Lai et al. (2019), glucocorticoid resistance and excessive systemic inflammation associated with this pathophysiological condition may manifest in the form of enhanced non-specific immunity and suppressed humoral immunity, which explains the increased susceptibility to inflammation-driven and infectious diseases in lonely individuals. The influence between loneliness and excessive inflammation seems to be bidirectional as experimental administration of an inflammatory challenge using endotoxin has been shown to induce a feeling of social disconnection in humans (Eisenberger et al., 2010).
This collection consists of seven papers with five empirical or preclinical and clinical studies, one review focusing on the behavioral and neurophysiological consequences of social isolation and loss (Vitale and Smith), and one perspective paper on the role of arginine vasopressin in human behaviors (Crespi et al.). In addition to reiterating findings on the association of social isolation and loneliness with altered endocrine-immune functioning or ill health, this collection may further our understanding of the complexity of this association by illuminating the effects of specific modulating factors on the health consequences of loneliness and social isolation in humans and animals. In a cross-sectional study with a mixed-sex sample of 79 seniors (mean age = 64.48 yrs., 40 women), Crespo-Sanmiguel et al. reported that loneliness was significantly associated with psychological and physical health in males, but not in females. Interestingly, these two variables had no relationship with cortisol indices including the cortisol awakening response (CAR), diurnal cortisol slope (DCS), and bedtime cortisol levels. As a result, cortisol indices did not mediate the connection between loneliness and poor health. In a separate study of 222 older adults from racially and socioeconomically diverse backgrounds (mean age = 76.82 yrs., 38% Black, 13% Hispanic), Van Bogart et al. examined the associations of loneliness—measured as a trait using a three-item loneliness scale and as an aggregated momentary feeling using an ecological momentary assessment (EMA) protocol—with basal plasmatic levels of inflammatory markers including C-reactive protein (CRP) and several cytokines, as well as LPS-stimulated levels of cytokines. A significant association was observed between trait and aggregated momentary loneliness and basal levels of CRP, a marker of systemic inflammation. This finding is consistent with the results reported in a recent meta-analytic review (e.g., Smith et al., 2020). The excessive inflammation associated with the lonely phenotype has also been verified by Nersesian et al. (2018) in a large prospective study.
Two papers in this collection focused on the behavioral and endocrine-immune effects of early-life social isolation in rodents (prairie voles) with (Sailer et al.) or without (Donovan et al.) concomitant exposure to a chronic stressor. The latter study demonstrated that social isolation had no effect on anxiety- and depression-like behaviors, but decreased the peripheral level of the pro-inflammatory cytokine IL-1β in isolated males compared to cohoused females. Social isolation also altered the density of microglia in specific regions of the brain, demonstrating that social isolation affected both peripheral and central markers of immunity. Although a main effect of social isolation on levels of IL-1β was not observed, the finding of a significant sex by treatment effect warrants further studies to get a better understanding of the impact of developmental social isolation on immune function. On the other hand, when a chronic stressor such as social defeat was combined with social isolation, animals exhibited social avoidance when tested on post-natal day 41. However, such behavior was not observed in some of the non-isolated (group-housed) animals exposed to chronic social defeat, thus supporting the idea that social support is a resilience factor. The effectiveness of a pharmacological intervention (intranasal oxytocin) has also been examined in adult Titi monkeys exposed to temporary separation from pair mates (Arias del Razo et al.). The protective effect of chronic treatment of oxytocin (daily intranasal oxytocin dose from 12 to 18 months of age) was clearly demonstrated in that treated animals exhibited a lower level of distress when exposed to separation compared to control animals chronically treated with saline. However, although cortisol levels increased in response to separation, these hormone levels did not differ between the chronically treated and control animals.
In conclusion, despite the limitations associated with each of the studies and the diversity of findings, taken together, the findings point to the complexity of the relationship of loneliness and social isolation with neuroendocrine and immune function. This calls for further research with increased attention to potential moderators such as sex and age because males have been found to be more susceptible to the negative mental health consequences of loneliness [e.g., depressive symptoms (Liu et al., 2020); low satisfaction with life and low resilience (Zebhauser et al., 2014); risk for developing dementia (Zhou et al., 2018)] and the negative health effects of loneliness seem to increase with age (e.g., Hawkley and Cacioppo, 2007). In addition, factors blunting the negative effects of isolation or separation such as social support (Sailer et al.) and oxytocin (Arias del Razo et al.) should also be given due attention. Further studies focused on the complexity of neural, physiological, and behavioral interactions, and interdisciplinary research with human samples and animal models (Crespi et al.; Vitale and Smith) will advance our understanding of social isolation and loneliness. Hopefully, this knowledge will promote more sensitive public health policies fostering early intervention approaches to tackle the negative health consequences associated with loneliness and social isolation.
Author contributions
JL contributed singly to summarizing the papers in this collection and writing of this editorial. All authors contributed to the article and approved the submitted version.
Funding
CV was the principal investigator of a project funded by Spanish Ministry of Science, Innovation and University (RTI2018-094627-B-I00). AG was supported in part by the National Institutes of Health (HL147179). The research input from JL was supported by General Research Fund of the University Grants Committee of Hong Kong (number 9042922).
Acknowledgments
We are grateful to the inputs from reviewers. This collection would not be realized without their dedication.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
References
Brown, E. G., Gallagher, S., and Creaven, A. (2018). Loneliness and acute stress reactivity: a systematic review of psychophysiological studies. Psychophysiology 55:e13031. doi: 10.1111/psyp.13031
Cacioppo, J. T., Cacioppo, S., Capitanio, J. P., and Cole, S. W. (2015), The neuroendocrinology of social isolation. Annu. Rev. Psychol. 66, 733–767. doi: 10.1146/annurev-psych-010814-015240
Cacioppo, S., Capitanio, J. P., and Cacioppo, J. T. (2014). Toward a neurology of loneliness. Psychol. Bull. 140, 1464–1504. doi: 10.1037/a0037618
Campagne, D. M. (2019). Stress and perceived social isolation (loneliness). Arch. Gerontol. Geriatr. 82, 192–199. doi: 10.1016/j.archger.2019.02.007
Eisenberger, N. I., Inagaki, T. K., Mashal, N. M., and Irwin, M. R. (2010). Inflammation and social experience: an inflammatory challenge induces feelings of social disconnection in addition to depressed mood. Brain Behav. Immun. 24, 558–563. doi: 10.1016/j.bbi.2009.12.009
Hawkley, L. C., and Cacioppo, J. T. (2003). Loneliness and pathways to disease. Brain Behav. Immun. 17, S98–S105. doi: 10.1016/s0889-1591(02)00073-9
Hawkley, L. C., and Cacioppo, J. T. (2007). Aging and loneliness. Downhill quickly? Psychol. Sci. 16, 187–191. doi: 10.1111/j.1467-8721.2007.00501.x
Hawkley, L. C., Cole, S. W., Capitanio, J. P., Norman, G. J., and Cacioppo, J. T. (2012). Effects of social isolation on glucocorticoid regulation in social mammals. Hormones Behav. 62, 314–323. doi: 10.1016/j.yhbeh.2012.05.011
Jeste, D. V., Lee, E. E., and Cacioppo, S. (2020). Battling the modern behavioral epidemic of loneliness: suggestions for research and interventions. JAMA Psychiatry 77, 553–554. doi: 10.1001/jamapsychiatry.2020.002
Lai, J. C. L., Lee, D. Y. H., Leung, M. O. Y., and Lam, Y. W. (2019). Daily hassles, loneliness, and diurnal salivary cortisol in emerging adults. Horm. Behav. 115:104558. doi: 10.1016/j.yhbeh.2019.07.006
Liu, H., Zhang, M., Yang, Q., and Yu, B. (2020). Gender differences in the influence of social isolation and loneliness on depressive symptoms in college students: a longitudinal study. Soc. Psychiatry Psychiatr. Epidemiol. 55, 251–257. doi: 10.1007/s00127-019-01726-6
Nersesian, P. V., Han, H. R., Yenokyan, G., Blumenthal, R. S., Nolan, M. T., Hladek, M. D., et al. (2018). Loneliness in middle age and biomarkers of systemic inflammation: findings from Midlife in the United States. Soc. Sci. Med. 209, 174–181. doi: 10.1016/j.socscimed.2018.04.007
Rico-Uribe, L. A., Caballero, F. F., Martin-Mana, N., Cabello, M., Ayuso-Mateos, J. L., and Miret, M. (2018). Association of loneliness with all-cause mortality: a meta-analysis. PLoS ONE 13:e0190033. doi: 10.1371/journal.pone.0190033
Smith, K. J., Gavey, S., Riddell, N. E., Kontari, P., and Victor, C. (2020). The association between loneliness, social isolation and inflammation: a systematic review and meta- analysis. Neurosci. Biobehav. Rev. 112, 519–541. doi: 10.1016/j.neubiorev.2020.02.002
Wang, J., Mann, F., Lloyd-Evans, B., Ma, R., and Johnson, S. (2018). Associations between loneliness and perceived social support and outcomes of mental health problems: a systematic review. BMC Psychiatry 18:156. doi: 10.1186/s12888-018-1736-5
Zebhauser, A., Hofmann-Xu, L., Baumert, J., Häfner, S., Lacruz, M. E., Emeny, R. T., et al. (2014). How much does it hurt to be lonely? Mental and physical differences between older men and women in the KORA-Age Study. Int. J. Geriatr. Psychiatry 29, 245–252. doi: 10.1002/gps.3998
Keywords: loneliness, social isolation (SI), cortisol, inflammation, immunity
Citation: Venero C, Grippo AJ and Lai JCL (2022) Editorial: Endocrinology of loneliness and social isolation. Front. Behav. Neurosci. 16:978386. doi: 10.3389/fnbeh.2022.978386
Received: 26 June 2022; Accepted: 26 July 2022;
Published: 10 August 2022.
Edited and reviewed by:
James Cherry, Boston University, United StatesCopyright © 2022 Venero, Grippo and Lai. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Julian C. L. Lai, c3NqdWx3aW4mI3gwMDA0MDtjaXR5dS5lZHUuaGs=