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Loneliness in middle age and biomarkers of systemic inflammation: Findings from Midlife in the United States
Abstract
Objective:
Middle-aged adults who are lonely have an elevated likelihood of death. Systemic inflammation may contribute to these increased odds. Using population-level data, this study tested if systemic inflammation is associated with loneliness in a broad age range of middle-aged adults in the United States.
Methods:
This study used data from the Midlife in the US (MIDUS) survey Biomarker Project, which collected data on psychological, social, and physiological measures from a sample of middle-aged adults. This sample included the 927 participants who were 35-64 years at Biomarker Project data collection. MIDUS collected baseline data from 1995-1996 and a follow-up survey was conducted from 2004-2006. The baseline Milwaukee sample of African Americans was collected in 2005-2006 and the biomarker database was collected in 2004-2009. Biomarkers were obtained from a fasting blood sample. Self-reported loneliness was categorized as feeling lonely or not feeling lonely. Hierarchical regressions examined the association between biomarkers of systemic inflammation (interleukin-6, fibrinogen, C-reactive protein) and feeling lonely, adjusted for covariates.
Results:
Twenty-nine percent of the sample reported feeling lonely most or some of the time. There was a positive significant relationship between loneliness and the three systemic inflammation biomarkers after controlling for covariates: interleukin-6 (n = 873) (b [se] = 0.07 [0.03], p = .014); fibrinogen (n = 867) (b [se] = 18.24 [7.12], p = .011); and C-reactive protein (n = 867) (b [se] = 0.08 [0.04], p = .035).
Conclusions:
Feeling lonely is associated with systemic inflammation in middle-aged community-dwelling US adults.
... Lonely persons have increased inflammation in Western samples (Eisenberger et al., 2017) and East Asian samples (S.-H. . Lonely middle-aged adults in the U.S. possess elevated levels of three systemic inflammation biomarkersinterleukin-6 (IL-6), fibrinogen, and C-reactive protein (CRP) -compared to their non-lonely counterparts (Nersesian et al., 2018). Loneliness was associated with higher inflammation in U.S. women compared to U.S. men (Hackett et al., 2012). ...
... Our study did not find a significant association between loneliness and inflammation. This result was curious because loneliness was positively associated with inflammation in a similar studywhich used secondary data from another wave of MIDUS survey (Nersesian et al., 2018). There are several reasons results might differ between our study and Nersesian et al. (2018). ...
... This result was curious because loneliness was positively associated with inflammation in a similar studywhich used secondary data from another wave of MIDUS survey (Nersesian et al., 2018). There are several reasons results might differ between our study and Nersesian et al. (2018). Data in the two projects were collected at different time points, and Nersesian et al. (2018) used data within a period that was more stressful than data collected in the current study (i. ...
... Single item measures of loneliness are strongly associated with the UCLA loneliness scale [29], and such single-item tools to quantify loneliness have favorable psychometric characteristics [30,31]. ...
... Limitations particularly refer to the cross-sectional design of the D80 + study. The item to quantify loneliness has a high face validity, has performed well in previous research, and is closely connected to multi-item scales [29]; however, it may not fully capture the complexity of the loneliness phenomenon (covering social and emotional loneliness). The single-item assessments of attachment and trust have on the living arrangement. ...
Objectives
To examine the association between perception of one’s social environment (in terms of residential attachment and neighborhood trust) and loneliness among the oldest old and whether these associations differ by living arrangement.
Methods
We used data from the nationally representative “Old Age in Germany (D80+)” study that included individuals residing in private households and institutionalized settings. The analytic sample was 9,621 individuals (average age: 85.5 years, SD: 4.1 years; 62% female). Data collection took place from November 2020 to April 2021. Multiple linear regressions were conducted with adjustment for relevant covariates.
Results
Higher residential attachment (β=-0.02, p < .05) and higher neighborhood trust (β=-0.12, p < .001) were associated with less loneliness. The latter association was moderated by living arrangement (β=-0.09, p = .04) such that the association between neighborhood trust and loneliness was stronger among individuals living in institutionalized settings compared to individuals in private households.
Conclusion
Greater residential attachment and neighborhood trust, particularly among individuals living in institutionalized settings, are associated with less loneliness among the oldest old. Finding ways to improve perceived attachment and trust may assist in avoiding loneliness among older individuals.
... Of the two, it is not clear which is the 'active ingredient' in predicting inflammatory outcomes. Studies focusing specifically on loneliness have yielded mixed results (Balter et al., 2019;Hackett et al., 2012;Mezuk et al., 2016;Nersesian et al., 2018;Pavela, Kim, and Salvy, 2018;Shiovitz-Ezra and Parag, 2019;Van Bogart et al., 2022), with most finding null associations. Those studies that have examined both isolation and loneliness in parallel (Shankar et al., 2011) suggest that objective social isolation, rather than loneliness, is the more relevant risk factor for inflammation outcomes. ...
... However, findings in younger adults were mixed, and suggested a role of familial confounding in the associations between social isolation or loneliness and inflammation at this stage of the lifespan. Previous studies have found associations between social isolation or loneliness with the traditional inflammation markers CRP and IL-6 (Van Bogart et al., 2022;Cudjoe et al., 2022;Hackett et al., 2012;Mezuk et al., 2016;Nersesian et al., 2018;Pavela et al., 2018;Shiovitz-Ezra and Parag, 2019). We found, in all three cohorts, that the novel biomarker suPAR yielded more consistent associations with social isolation than the more commonly used CRP and IL-6. ...
... Consistent with these notions, a recent review and metaanalyses conducted in individuals aged 16 or older from the general population found evidence supporting the link between inflammation and loneliness, though this publication noted limitations with regards to methodological heterogeneity across studies ). Many of the available loneliness studies examined biomarkers of systemic inflammation that have been linked to downstream health-related consequences such as increased cardiovascular risk ; these inflammatory processes include cytokines (e.g., interleukin-6 [IL-6]), chemokines (e.g., chemokine (C-C motif) ligand 2/monocyte chemoattractant protein-1 [CCL2/MCP-1]) and acute phase proteins (e.g., C-reactive protein [CRP]; Hackett et al. 2012;Leschak and Eisenberger 2019;Nersesian et al. 2018;Smith et al. 2020). ...
... Previous studies have linked loneliness to elevated levels of CCL2/MCP-1 in PWoH (Hackett et al. 2012(Hackett et al. , 2019, though to our knowledge no studies have examined associations between loneliness and D-dimer or sCD14. Nersesian et al. (2018) found an association between levels of fibrinogen, which, with D-dimer can lead to a hypercoagulable state, and loneliness in PWoH. Associations between loneliness and social support, as well as with comorbid substance use disorders, has been reliably demonstrated in the literature Stanton et al. 2015). ...
Objective:
Loneliness is prevalent in people with HIV (PWH) and associated with adverse health-related consequences, including depression. Chronic inflammation has been linked to depression in PWH, though its association with loneliness is less well established. Simultaneous examination of inflammation, loneliness and depression is needed to clarify these relationships. This study investigated the relationship between loneliness and inflammation, and the effects of loneliness and inflammation on depression in PWH.
Methods:
82 PWH who were on suppressive ART (mean age [SD] = 53.2 [9.0]) completed the UCLA Loneliness Scale-Version 3 and the Center for Epidemiologic Studies Depression Scale as part of a comprehensive evaluation. Biomarkers of systemic inflammation (CRP, IL-6, CCL2/MCP-1, sCD14) and coagulation (D-dimer) were measured in blood using commercial immunoassays.
Results:
Multivariable linear regression analyses revealed that higher D-dimer, CCL2/MCP-1, and sCD14 were significant predictors of loneliness (ps < .05) while accounting for relevant covariates. Stepwise multiple linear regression models that included loneliness, biomarkers, and their interactions as predictors of depressive symptoms revealed significant main effects of loneliness and CCL2/MCP-1 levels (ps < .05), and a significant loneliness by D-dimer interaction (p < .05) whereby higher D-dimer was associated with increased depressive symptoms only at higher levels of loneliness.
Conclusions:
Increased coagulation activity is associated with loneliness, and in the context of loneliness, may increase risk for depression. Increased inflammation was associated with depression suggesting potentially dissociable underlying biological processes. To the extent that these processes are modifiable, such findings could have important implications in the treatment of loneliness and depression in PWH.
... Lastly, loneliness could elicit heightened low-grade systemic inflammation, through elevating c-reactive protein (CRP). 24,25 Apart from having significant associations with loneliness, these biomarkers have also been shown to be risk factors for and precede CI and dementia onset. [16][17][18]26,27 On the other hand, contradictory empirical and meta-analytic findings separately associating loneliness with biomarkers and CI persist in the literature, with some studies showing non-significant associations. ...
... However, it is noteworthy that many of the evidence were gleaned from studies of cross-sectional nature. [19][20][21][22][23][24][25] In our study, we validated the presence of significant cross-sectional associations between all biomarkers separately with loneliness and cognitive status (see Table 2-correlation matrix of main variables). However, in the model without covariates, except HbA1C, loneliness did not have significant prospective associations with all four other biomarkers. ...
BACKGROUND
Loneliness precedes the onset of cognitive impairment (CI) in older adults. Although the mechanisms through which loneliness “gets under the skin” to influence the risk of developing CI has been conceptually proposed, they are rarely empirically examined. The Evolutionary Theory of Loneliness posits that loneliness as a stressor could cause dysregulations in multiple physiological systems. The current study investigated whether inflammatory, cardiovascular, and kidney biomarkers mediate the longitudinal association between loneliness and CI.
METHODS
Cross-lagged panel models (CLPM) were used to examine the hypothesized relationships, using 2006, 2010, and 2014 waves of data from the Health and Retirement Study (N=7,037). Loneliness was measured with the 3-item UCLA loneliness scale. CI was assessed with the modified telephone interview for cognitive status. Biomarkers included HbA1C, LDL cholesterol, HDL cholesterol, CRP, and Cystatin C. Using a stepwise model-building approach, first, the model included only loneliness, CI, and biomarker variables; then, sociodemographic covariates were added; lastly, health and behavioral covariates were controlled for.
RESULTS
In unadjusted and partially adjusted models, loneliness was associated with higher odds of worse cognitive status in an 8-year follow-up. Only HbA1C mediated the longitudinal association between loneliness and CI. However, after further controlling for health status, all associations became non-significant.
CONCLUSIONS
Examining a large number of participants and linking a limited number of biological markers with cognition and loneliness longitudinally, our empirical data did not support theoretical propositions, highlighting the critical importance of controlling for confounders in future studies examining longitudinal mediational relationships underlying loneliness and CI.
... T. Cacioppo & Cacioppo, 2018). Health consequences of loneliness can include increased functional decline (Nersesian et al., 2018;Perissinotto et al., 2012), deterioration of physical (Holt-Lunstad & Smith, 2016) and psychological health (Gray et al., 2020), suicide (Stickley & Koyanagi, 2016), and death (Holt-Lunstad et al., 2015;Perissinotto et al., 2012). The risk of premature mortality was increased by 26% with loneliness (J. ...
... These study findings showed that older adults who had higher coping self-efficacy have significantly decreased odds of loneliness, though this association was not dramatically altered by adjusting for social support or depressive symptoms. This finding is particularly salient since research into loneliness has traditionally focused on deficits to explain symptoms of loneliness (Nersesian et al., 2018). A systematic concept analysis of loneliness identified three critical attributes to consider: (1) a subjective perception of psychological discomfort, (2) dissatisfaction with the quantity and quality of existing relationships, and (3) an interpretation of one's inability to reconcile this sense of dissatisfaction through corrective actions (ElSadr et al., 2009). ...
To address the gap of lacking research on the association between coping self-efficacy and loneliness, this study examined this relationship to inform future research and intervention on loneliness. Using data from 151 community-dwelling older adults ages 65 and older, we estimated multivariate logistic regression models with age, race/ethnicity, sex, body mass index, chronic disease composite score, social support, coping self-efficacy, and depression symptoms. Loneliness was reported in 32.1% of participants and negatively associated with coping self-efficacy (OR = 0.68, 95% CI: 0.50–0.93) while controlling for age, race, sex, chronic disease composite score, and body mass index. Our findings suggest that coping self-efficacy may be a target for intervention involving loneliness in future research; however, the causal relationship between coping self-efficacy and loneliness should be explored further.
... However, findings from studies linking loneliness to systemic, circulating inflammatory markers are less consistent. Some studies have reported significant associations between loneliness and higher circulating (basal) levels of inflammatory markers (Nersesian et al., 2018;Zilioli and Jiang, 2021), but there are also null findings in this literature (Hackett et al., 2012;Mezuk et al., 2016;Zilioli and Jiang, 2021). A recent meta-analysis found that a significant association between loneliness and circulating IL-6 levels has been observed consistently, whereas associations between loneliness and C-reactive protein (CRP) or fibrinogen have not been consistent (Smith et al., 2020). ...
... (or, in exploratory analyses, with individual cytokines). Our findings are in contrast to past work linking loneliness to higher cytokine levels during midlife (Nersesian et al., 2018) and past null findings with CRP for adults ages 18-85 years old (for meta-analysis, see: Smith et al., 2020). However, our results are in line with past longitudinal work that has found significant associations between trait loneliness and CRP among different age samples [50-99 years: (Vingeliene et al., 2019) and 50-67 years: (Cole et al., 2007)]. ...
Loneliness has been linked to poor mental and physical health outcomes. Past research suggests that inflammation is a potential pathway linking loneliness and health, but little is known about how loneliness assessed in daily life links with inflammation, or about linkages between loneliness and inflammation among older adults specifically. As part of a larger investigation, we examined the cross-sectional associations between loneliness and a panel of both basal and LPS-stimulated inflammatory markers. Participants were 222 socioeconomically and racially diverse older adults (aged 70–90 years; 38% Black; 13% Hispanic) systematically recruited from the Bronx, NY. Loneliness was measured in two ways, with a retrospective trait measure (the UCLA Three Item Loneliness Scale) and an aggregated momentary measure assessed via ecological momentary assessment (EMA) across 14 days. Inflammatory markers included both basal levels of C-reactive protein (CRP) and cytokines (IL-1β, IL-4, IL-6, IL-8, IL-10, TNF-α) and LPS-stimulated levels of the same cytokines. Multiple regression analyses controlled for age, body-mass index, race, and depressive symptoms. Moderation by gender and race were also explored. Both higher trait loneliness and aggregated momentary measures of loneliness were associated with higher levels of CRP (β = 0.16, p = 0.02; β = 0.15, p = 0.03, respectively). There were no significant associations between loneliness and basal or stimulated cytokines and neither gender nor race were significant moderators. Results extend prior research linking loneliness with systemic inflammation in several ways, including by examining this connection among a sample of older adults and using a measure of aggregated momentary loneliness.
... Social isolation and loneliness, acting as social stressors, can trigger stress responses, involving the SNS and HPA axis, leading to altered immune function 44 . Indeed, social isolation and loneliness have been shown to be associated with heightened proinflammatory activity, manifested by elevated levels of inflammation biomarkers such as IL6, fibrinogen and CRP [45][46][47] . In addition to inflammation, the SNS and HPA axis may also modulate antiviral responses. ...
The biology underlying the connection between social relationships and health is largely unknown. Here, leveraging data from 42,062 participants across 2,920 plasma proteins in the UK Biobank, we characterized the proteomic signatures of social isolation and loneliness through proteome-wide association study and protein co-expression network analysis. Proteins linked to these constructs were implicated in inflammation, antiviral responses and complement systems. More than half of these proteins were prospectively linked to cardiovascular disease, type 2 diabetes, stroke and mortality during a 14 year follow-up. Moreover, Mendelian randomization (MR) analysis suggested causal relationships from loneliness to five proteins, with two proteins (ADM and ASGR1) further supported by colocalization. These MR-identified proteins (GFRA1, ADM, FABP4, TNFRSF10A and ASGR1) exhibited broad associations with other blood biomarkers, as well as volumes in brain regions involved in interoception and emotional and social processes. Finally, the MR-identified proteins partly mediated the relationship between loneliness and cardiovascular diseases, stroke and mortality. The exploration of the peripheral physiology through which social relationships influence morbidity and mortality is timely and has potential implications for public health.
... Loneliness was measured based on a commonly administered (Mund et al., 2022) single-item tool ranging from 1 (never/almost never) to 4 (always/almost always). The sensitivity of such measures and a high correlation with the UCLA has been shown (Nersesian et al., 2018). Moreover, favorable psychometric properties have been demonstrated (Mund et al., 2022). ...
Aim
Our aim was to identify multimorbidity clusters and, in particular, to examine their contribution to well-being outcomes among the oldest old in Germany.
Methods
Data were taken from the large nationally representative D80+ study including community-dwelling and institutionalized individuals aged 80 years and over residing in Germany(n=8,773). The mean age was 85.6 years (SD: 4.1). Based on 21 chronic conditions, latent class analysis was carried out to explore multimorbidity (≥2 chronic conditions) clusters. Widely used tools were applied to quantify well-being outcomes.
Results
Approximately nine out of ten people aged 80 and over living in Germany were multimorbid. Four multimorbidity clusters were identified: relatively healthy class (30.2%), musculoskeletal class (44.8%), mental illness class (8.6%), and high morbidity class (16.4%). Being part of the mental disorders cluster was consistently linked to reduced well-being (in terms of low life satisfaction, high loneliness and lower odds of meaning in life), followed by membership in the high morbidity cluster.
Conclusions
Four multimorbidity clusters were detected among the oldest old in Germany. Particularly belonging to the mental disorders cluster is consistently associated with low well-being, followed by belonging to the high morbidity cluster. This stresses the need for efforts to target such vulnerable groups, pending future longitudinal research.
... These indicators have mainly been used in biosocial research (e.g. Kavanagh et al. 2010;Chandola and Zhang 2018;Nersesian et al. 2018;Walker et al. 2019) to understand how a range of exposures may impact biological systems and bring about health status. For example, group drumming (Bittman et al. 2001), singing (Fancourt et al. 2016b), music listening (Finn and Fancourt 2018), and gallery (Clow and Fredhoi 2006) and concert attendance have each been shown to be associated with reduced levels of the stress hormone cortisol. ...
Background
Research has shown that cultural activities may bring about improved health. However, large-scale quantitative analyses on cultural engagement and biomarkers are lacking to date. As a result, the mechanisms through which cultural activities may be associated with health are unclear.
Aim
Test quantitative associations between cultural engagement pattern (including active and passive engagement in arts, sports, and heritage activities) and indicators of biological dysregulation in a large dataset.
Subjects and methods
Understanding Society data were used to conduct cross-sectional linear regression analyses between a data-driven latent class model of cultural engagement and indicators of anthropometric, cardiovascular, metabolic, immune, and neuroendocrine function. Analyses were adjusted for age, gender, ethnicity, childcare responsibility, urbanicity, leisure time satisfaction, capacity-related factors, socioeconomic position, social and economic capital indicators, physical activity, and medication use.
Results
More culturally participants had better indicators of biological health, such as lower waist circumference and fibrinogen blood concentration. Specific associations between cultural engagement pattern and the different biological outcomes were also observed. The associations were explained in part by correlated factors (accounting for around half of the association).
Conclusions
Cultural engagement is cross-sectionally associated with biomarkers, although the characteristics of people who engage with culture are an important consideration when interpreting these findings.
... They found that people who reported loneliness were more likely than those who did not report loneliness to suffer more chronic stressors (33), perceive daily events as stressful (34), and experience increased activation of the sympathetic nervous system (13,35). The latter involves prolonged stimulation of the hypothalamus-pituitary-adrenal axis (30,31,36), which contributes to systemic inflammation (37), physical decline (38) and in turn, the likelihood of pain onset and worsening of pain intensity. ...
Background
Prior research has demonstrated a strong and independent association between loneliness and pain, but few studies to date have explored this relationship in racially and ethnically diverse groups of midlife and older adults. We drew on the diathesis stress model of chronic pain and cumulative inequality theory to examine the relationship of loneliness and the presence and intensity of pain in a nationally representative sample of Black, Latino, and White adults aged 50 or older in the United States.
Methods
Data were from Wave 3 of the National Social Life, Health, and Aging Project (n = 2,706). We used weighted logistic and ordinary least squares regression analyses to explore main and interactive effects of loneliness and race and ethnicity while adjusting for well-documented risk and protective factors (e.g., educational attainment, perceived relative income, inadequate health insurance, perceived discrimination) and salient social and health factors.
Results
Almost half (46%) of the participants reported feeling lonely and 70% reported the presence of pain. Among those who reported pain (n = 1,910), the mean intensity score was 2.89 (range = 1–6) and 22% reported severe or stronger pain. Greater loneliness was associated with increased odds of pain presence (AOR = 1.154, 95% CI [1.072, 1.242]) and higher pain intensity (β = 0.039, p < 0.01). We found no significant interaction effects involving Black participants. However, Latino participants who reported greater loneliness had significantly higher levels of pain (β = 0.187, p < 0.001) than their White counterparts with similar levels of loneliness.
Discussion
Loneliness is an important correlate of pain presence and intensity and may have a stronger effect on pain intensity among Latino adults aged 50 or older. We discuss clinical and research implications of these findings, including the need for more fine-grained analyses of different types of loneliness (e.g., social, emotional, existential) and their impact on these and other pain-related outcomes (e.g., interference). Our findings suggest a need for interventions to prevent and manage pain by targeting loneliness among middle-aged and older adults, particularly Latino persons.
... Moreover, a graduate student working with me, Karina Van Bogart, has focused on the connection between loneliness and biobehavioral health. Building on past research linking loneliness with inflammation [e.g., [78][79][80]], which has primarily been conducted using retrospective measures of loneliness and in younger or midlife samples, Van Bogart spearheaded work in which she revealed a connection between aggregated momentary loneliness and CRP among older adults [81], who as a group are particularly vulnerable to both loneliness and inflammation-related sequalae [82,83]. Van Bogart and multiple other individuals with whom I have been involved as a mentorincluding Jee eun Kang, Karra Harrington, and Dakota Witzelhave led multiple other novel lines of inquiry related to loneliness, all involving midlife or older adults [77,[84][85][86]. ...
The term “affective immunology” has recently been used to denote a field focused on the interplay between affective processes (including mood states, specific emotions, and regulatory processes) and various aspects of immune function. The overarching goals of this commentary are a) to provide historical underpinnings of this field with a focus on the profound impact of the work of Janice Kiecolt-Glaser, who is further honored in this special issue, b) to review important off-shoots of her legacy work in this domain, and c) to highlight important future directions for the field. Kiecolt-Glaser's work laid much of the foundation for affective immunology, with groundbreaking research related to depression, hostility and dyadic interactions, loneliness, and other affective patterns, often in the context of holistic models, novel experimental designs, and interventions. Her former mentees (and many of their mentees) have carried on her legacy in these domains, in ways that continue to advance appreciation of how affective processes relate to immune function. There are numerous remaining questions for the field to pursue, including better understanding of the role of emotion regulation, emotional reactivity and recovery, restorative processes, affective variability, and developmental and dynamic social processes. Such work will require greater use of longitudinal and within-person approaches and/or examination of processes in daily life, as well as models that account for interactive and reciprocal processes and which integrate behavior, social context, sociocultural factors, individual differences, and other aspects of health. As more work in these domains continues, building on Kiecolt-Glaser's rich legacy, we move toward the emergence of affective immunology as an important subfield in the domain of psychoneuroimmunology, one which will offer more nuanced understanding of the role of affective processes in immune health.
... The connection between the brain and the immune system has been extensively studied in the literature, showing that peptides are systematically involved [21]. Inflammatory markers have been associated with psychological stress conditions, such as loneliness, in the general population, demonstrating associations with increased body mass index (BMI), interleukins, and C-reactive protein (CRP) [22][23][24]. Additional indices routinely evaluated for a complete assessment of inflammation status include sedimentation rate (ESR), ferritin, and albumin [25]. ...
... Single items are commonly used to assess loneliness [19]. Furthermore, previous research has indicated the sensitivity of this measurement and its strong correlation with the UCLA loneliness scale [20]. The reliability and validity of this measure have also been demonstrated in other research [19]. ...
Background
The COVID-19 pandemic engendered numerous societal and economic challenges in addition to health-related concerns. Maintenance of healthcare utilization assumed immense significance during this period. However, few studies have examined the association between loneliness and cancelled medical appointments during the COVID-19 pandemic. This study aimed to examine whether medical appointments are less likely to be cancelled with increased loneliness during a pandemic. We analyzed the association between loneliness and both patient- and provider-initiated appointment cancellations.
Methods
Cross-sectional data from the Hamburg City Health Study (HCHS) were collected during April 2020–November 2021. The analytical sample included 1,840 participants with an average age of 55.1 years (standard deviation: 6.5, range 45–76 years). Medical appointments cancelled by individuals—medical appointments in general, and GP, specialist, and dentist appointments—and appointments cancelled by healthcare providers served as outcome measures. Loneliness was quantified using a single item ranging from 0 to 10. Accordingly, we created empirical loneliness tertiles. Covariates were selected based on the Andersen model. Several penalized maximum likelihood logistic regressions were utilized to examine the association between loneliness and cancellation of medical appointments during the COVID-19 pandemic.
Results
The penalized maximum likelihood logistic regressions showed that, compared to individuals in the lowest loneliness tertiles, individuals in the other two tertiles reported a higher chance of medical appointments cancellation by individuals, particularly driven by cancelled GP appointments. Except for age and sex, none of the covariates were comparably associated with the outcomes. When appointments cancelled by healthcare providers served as outcomes, only a higher number of chronic conditions was significantly positively associated with it.
Conclusions
Individuals scoring higher in loneliness had a greater chance of cancelling medical (particularly GP) appointments. This may contribute to a potential cascade of loneliness and skipped medical appointments in the future, resulting in adverse health outcomes over the medium-to-long term. Future research should examine whether lonely people are more likely to lack the social motivation to visit the doctor.
... 13,14,15,16 Moreover, research has demonstrated associations between loneliness and greater risks of physical and mental health conditions, 12 including high blood pressure, depression, anxiety, and cognitive decline. 17,18,19,20 Extant research on approaches to reduce what has been called "structural loneliness," 21 while yielding mixed results, points to the importance of education, social cognition, and opportunities for social connection. 22,23 However, when designing interventions for loneliness, few researchers consider the impact of societal structures or contexts that influence interpersonal relationships and opportunities to connect among immigrant communities. ...
Cultural brokers can help clinicians meet needs of immigrant patients. This article considers loneliness as an endemic experience of immigrants in the United States and discusses how cultural brokerage practices can reduce the ill health effects of loneliness by helping clinicians contextualize their interactions with immigrant patients and by helping immigrants navigate the health care system and build social connections.
... Biological plausibility for the association between loneliness and mortality is supported by emerging evidence. Loneliness may induce dysregulation of systemic inflammation (25), elevated blood pressure (26), accelerated memory aging (9), and worse cardiovascular health (27), leading to premature mortality. Loneliness has been associated with poor health outcomes and increased health care utilization, such as hospitalization and emergency visits, among individuals with heart failure (28). ...
Loneliness is a growing public health concern worldwide. We characterized the association between cumulative loneliness and subsequent all-cause mortality, using data from 9,032 participants aged 50+ in the population-based US Health and Retirement Study (HRS) from 1996 to 2019. Loneliness status (yes; no) was measured biennially from 1996 to 2004, and we categorized the experience of cumulative loneliness over the 8-y period as never, one time point, two time points, and ≥three time points. A multivariable-adjusted age-stratified Cox proportional hazards regression model was fitted to examine the association between cumulative loneliness from 1996 to 2004 and all-cause mortality from 2004 to 2019. Excess deaths due to each category of cumulative loneliness were calculated. Compared to those who never reported loneliness from 1996 to 2004, participants experiencing loneliness at one time point, two time points, and ≥three time points respectively had 1.05 (95% CI: 0.96 to 1.15), 1.06 (95% CI: 0.95 to 1.19), and 1.16 (95% CI: 1.02 to 1.33) times higher hazards of mortality from 2004 to 2019 (P trend = 0.01). These results correspond to 106 (95% CI: 68 to 144), 202 (95% CI: 146 to 259), and 288 (95% CI: 233 to 343) excess deaths per 10,000 person-years, for those experiencing loneliness at each of one, two, or ≥three time points from 1996 to 2004. Cumulative loneliness in mid-to-later life may thus be a mortality risk factor with a notable impact on excess mortality. Loneliness may be an important target for interventions to improve life expectancy in the United States.
... Loneliness and social isolation have been associated with health risks including coronary heart disease, type 2 diabetes, stroke, and premature mortality (Christiansen et al., 2021;Holt-Lunstad et al., 2015;Steptoe et al., 2013;Valtorta et al., 2016). Loneliness and social isolation have also been linked to increased risk of infections (Elovainio et al., 2023), engagement in harmful health-related behaviors (Kobayashi & Steptoe, 2018;Shankar et al., 2011), and increases in health-related risk factors such as blood pressure and systemic inflammation (Nersesian et al., 2018;Shankar et al., 2011). In short, loneliness and social isolation are associated with various health risks within the general population. ...
Objective:
This study examined education, partnership status, and the moderating role of the lockdown period on social connectedness during the COVID-19 pandemic in a sample of urban African-American older adults.
Methods:
Five hundred thirty-four African-American adults living in Detroit (91.0% female, Mage = 74.53) reported demographic information pre-pandemic and answered one social connectedness questionnaire between April and December 2020.
Results:
Participants interviewed after the lockdown (post-June 2020) reported more loneliness than those interviewed during the lockdown (April-June, 2020). Married/partnered participants reported less loneliness and social isolation. Loneliness did not differ between those with high education levels interviewed during the lockdown compared to post-lockdown. However, among individuals with low education levels, those interviewed after the lockdown reported more loneliness than those interviewed during the lockdown period.
Conclusion:
Our findings suggest partnership status is associated with more social connectedness during the pandemic and education accentuates the effects of forced isolation related to loneliness among urban African-American older adults.
... Project have also shown that loneliness is associated with elevated inflammatory markers, including IL-6, fibrinogen, and C-reactive protein, among adults aged 35 to 64 years old (14). ...
Full text at: https://midus.wisc.edu/findings/pdfs/2778.pdf
Objective
Loneliness is linked to interleukin-6 (IL-6), a marker of systemic inflammation, which chronically has deleterious effects on physical and mental health across the adult life span. This study investigated cross-sectional relationships among loneliness, IL-6, demographics, multimorbidity, depression, obesity, friendship quantity, and slowed gait.
Methods
Data from the MIDUS Biomarker Project, a national adult sample (N = 822, age range: 26-78 years) was used for this study. The PROCESS macro tested the hypothesis that IL-6 would mediate the relationship between loneliness and gait, after adjusting for demographic and health risk factors.
Results
Age (ß = .292, p < .001), sex (ß = .197, p < .001), body mass index (BMI: ß = .374, p < .001), waist-hip-ratio (ß = .242, p < .001), and loneliness (ß = .089, p = .025) but not multimorbidity (ß = .043, p = .20), depression history (ß = .022, p = .47), depression symptoms (ß = .036, p = .28), and number of friends (ß = .022, p = .46) contributed to the variance in IL-6. Serial mediation analyses supported the chained effect of loneliness on walking time through BMI and IL-6. Results also showed specific indirect effects of BMI and IL-6 on walking time, suggesting more than one pathway by which loneliness influences health.
Conclusions
These results suggest that loneliness may increase the risk of systemic inflammation, leading to slowed gait and adverse health outcomes. Psychosocial interventions that address loneliness may provide an optimal treatment target for reducing inflammation and preventing declines in health.
... It ranges from 1 (never/almost never) to 4 (always or almost always). Prior research has shown that the UCLA loneliness scale is highly associated with such a single item measure of loneliness [33]. ...
Background:
There is very limited knowledge regarding the prevalence and determinants of loneliness in oldest old residents of nursing or old age homes.
Objective:
To examine the prevalence and determinants of loneliness among the oldest old living in institutionalized settings in Germany.
Material and methods:
Data were taken from the representative survey on quality of life and subjective well-being of the very old in North Rhine-Westphalia (NRW80+) including individuals ≥ 80 years living in North Rhine-Westphalia. The study focused on individuals living in institutionalized settings. Sociodemographic, lifestyle-related, and health-related determinants were included in multiple linear regression models.
Results:
Approximately 56.6% of the individuals were not lonely, 25.7% and 17.8% of the individuals were moderately and severely lonely, respectively. Regression analyses showed that higher loneliness was associated with being married (β = 0.48, p < 0.05), high education (compared to low education, β = 0.46, p < 0.05), having a small social network size (β = -0.02, p < 0.05), having poor self-rated health (β = -0.25, p < 0.05), and more depressive symptoms (β = 0.25, p < 0.001).
Conclusion:
A significant proportion of the institutionalized oldest old individuals reported moderate or severe loneliness, which underpins the relevance of this topic. Understanding the determinants of loneliness may help to address institutionalized adults aged 80 years and over at risk of loneliness.
... According to the subgroup analysis, people aged 35 to 49 made the positive relationship between renal calculi and CircS more significant. Although many lines of evidences indicate that the elderly account for the largest portion of CircS, numerous analyses support that these middleaged populations are more easily to develop metabolism disorders and kidney stones in times of rapid change [38,39]. Mounting evidence shows that the highest odds of kidney stones were seen for people aged 40 to 69 [40,41], and these middle-aged people, especially overweight people, prefer to develop sleep disorders and psychological problems such as depression and anxiety [42]. ...
Objective
To explore the association between circadian syndrome (CircS) and the prevalence of kidney stones in overweight people.
Materials and methods
A cross-sectional analysis was conducted based on the NHANES 2007–2018. Overweight people aged ≥ 20 years were the target population. Three multivariable logistic regression models were built to examine the association between CircS and kidney stones. Subgroup analysis based on age, gender, and race were also employed. Interaction and stratification analysis was also conducted to identify whether some factors modify the association.
Result
A total of 4,603 overweight participants were included in the study. The multivariable logistic regression suggested that CircS was positively associated with the prevalence of kidney stones (OR = 1.422, 95% CI 1.057 to 1.912). The subgroup analysis showed that the association was more obvious in females (OR = 1.604, 95% CI 1.023 to 2.516) or in the population aged 35 to 49 years old (OR = 2.739, 95% CI 1.428 to 5.254). Additionally, the same trend was present when people were Mexican American (OR = 3.834, 95% CI 1.790 to 8.215) or other races (OR = 4.925, 95% CI 1.776 to 13.656). The interaction and stratification analysis showed that the results above were robust.
Conclusion
CircS was positively associated with the prevalence of kidney stones in overweight people, especially people as females, aged 35 to 49, and Mexican Americans.
... Being lonely increases the probability of medication for stomach pain by 11%, and for inflammation by 6%. This result is consistent with the existing literature showing that some markers of systematic inflammation are higher among lonely individuals (Nersesian et al., 2018;Smith et al., 2020), which, in turn, may increase the risk of cardiovascular diseases and other physical health issues and functional decline. ...
Loneliness is increasingly being recognized as an important economic and public health issue. This paper investigates the relationship between historically rooted norms that drive individuals to conform to predefined behavioral standards and contemporary perceptions of social interactions and attitudes towards loneliness. Using a sub-population of second-generation immigrants, we identify an intergenerationally transmitted component of culture that reflects the importance of restrained discipline and rules characterizing highly intensive pre-industrial agricultural systems. We show that this cultural dimension influences perceptions of the quality of social relationships and significantly affects the likelihood of experiencing loneliness. The identified trait is then used to instrument loneliness in a two-stage model for health. We find that loneliness directly affects body mass index and some specific mental health issues. We argue, however, that loneliness may influence other health outcomes indirectly due to its economically significant effect on the increased body mass index. The results are robust to a battery of sensitivity checks. Our findings add to a growing body of research on the importance of attitudes in predicting significant economic and health outcomes, opening up a new channel via which deeply-rooted geographical, cultural, and individual characteristics may influence comparative economic development processes.
... Loneliness was measured using a signaling question ("Do you experience feelings of loneliness?"), This measurement method has been widely used in studies worldwide as a quick measure of loneliness [43][44][45]. There were four answers to the question: (1) none, (2) rarely, (3) sometimes, and (4) often. ...
Strong relationship exists between loneliness and depression in older adults. However, the effect of multifaceted social relationships on the relationship between loneliness and depression has not been explored. The purpose of the current study was to find out how multifaceted social relationships affect the aforementioned processes. We investigated and evaluated the loneliness status, depression symptoms, social relationships, and demographic information of 1116 older adults aged ≥65 years living in rural Japan. The final 555 participants were included in the analysis. Statistical evidence showed a direct effect between loneliness and depression symptoms. Additionally, the mediation model found that social curiosity and participation acted as mediators between loneliness and depression symptoms. Further, independence and participation, independence, and feeling safe played a conditional moderating role in the model of loneliness–social curiosity–depression symptoms and loneliness–participation–depression symptoms, respectively. Interaction can be an individual moderator in the link between loneliness and depression symptoms without any mediator. The moderated mediation model suggests that social curiosity and participation could mediate the association between loneliness and depression symptoms. In this process, independence, participation, and feeling safe may act as moderators.
... At a deeper physiological level, inflammatory processes may provide a logical link between loneliness and accelerated aging in PTSD. Elevated inflammatory indices such C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNFα), have been found associated with loneliness [107][108][109][110] and with PTSD [111][112][113][114][115][116][117][118][119][120][121][122][123][124][125][126]. The same is true of elevated indices of oxidative damage [127][128][129]. ...
Prior research suggests that people with Posttraumatic Stress Disorder (PTSD) may experience a form of accelerated biological aging. In other populations, loneliness has been shown to elevate risk for many of the same components of accelerated biological aging, and other deleterious outcomes, as seen in people with PTSD. Although standard diagnostic criteria for PTSD include “feelings of detachment or estrangement from others”, the relationship of such feelings to the concept of loneliness remains uncertain, in par potentially due to a failure to distinguish between loneliness versus objective social isolation. In order to catalyze wider research attention to loneliness in PTSD, and the potential contribution to accelerated biological aging, the present paper provides three components: (1) a conceptual overview of the relevant constructs and potential interrelationships, (2) a review of the limited extant empirical literature, and (3) suggested directions for future research. The existing empirical literature is too small to support many definitive conclusions, but there is evidence of an association between loneliness and symptoms of PTSD. The nature of this association may be complex, and the causal direction(s) uncertain. Guided by the conceptual overview and review of existing literature, we also highlight key areas for further research. The ultimate goal of this line of work is to elucidate mechanisms underlying any link between loneliness and accelerated aging in PTSD, and to develop, validate, and refine prevention and treatment efforts.
... Immune system dysfunction may be a common physiological correlate of loneliness and symptom clusters and, thus, may partially explain the mechanism by which loneliness may lead to high symptom burden. People who were lonely had increased proinflammatory cytokines and glycoproteins, such as interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), interleukin-1 receptor antagonist (IL-1Ra), monocyte chemoattractant protein 1 (MCP-1), fibrinogen, and C-reactive protein (CRP) [39][40][41]. A growing body of research has proposed that acute or chronic inflammation may underlie the symptom clusters. ...
Background
A symptom cluster is a group of two or more symptoms that occur together and are related to each other. Family caregivers of allogeneic hematopoietic stem cell transplant (HSCT) recipients experience multiple concurrent symptoms, but the majority of symptom research in this population has focused on assessing and managing individual symptoms.
Objectives
The purpose of this analysis was to determine (1) if clusters of five highly prevalent symptoms (fatigue, sleep disturbance, depression, anxiety, and cognitive impairment) in allogeneic HSCT caregivers could be identified and (2) what caregiver and patient characteristics influence membership in the identified symptom cluster groups.
Study Design
Baseline cross-sectional data were collected from allogeneic HSCT caregivers participating in a randomized controlled trial at the National Institutes of Health Clinical Center. Measures included: Caregiver Reaction Assessment (CRA), the Health-Promoting Lifestyle Profile II (HPLP-II), Fatigue Symptom Inventory (MFSI), Pittsburgh Sleep Quality Index (PSQI), and PROMIS® (depression, anxiety, applied cognition, and self-efficacy). Cluster analysis was used to identify symptom clusters, and univariate analyses and multiple logistic regression were conducted to identify factors that contribute to symptom clusters.
Results
Caregivers’ (N=44) were on average 45.20 ± 15.05 years; primarily white (52.3%), female (88.6%), and spouse/partner of the patient (50.0%). Two symptom cluster groups were identified: low symptom burden (n=24, 54.5%) and high symptom burden (n= 20, 45.5%). Caregivers with higher levels of loneliness (OR = 1.12, CI = [1.04, 1.22], p = .004) were more likely to be in the high symptom burden group.
Conclusions
This study provides evidence that five symptoms commonly found in family caregivers (fatigue, sleep disturbance, depression, anxiety, and cognitive impairment) tend to occur in clusters. Therefore, clinicians should be aware that caregivers experiencing one or more of these symptoms may be at higher risk for developing the others, and caregivers reporting high levels of loneliness may be at particular risk. Future research is needed to identify novel interventions that target multiple, co-occurring symptoms. Such interventions might also include components that decrease loneliness.
... Furthermore, we included loneliness using a single item measure (from 1= never/almost never to 4 = almost or almost always; with higher values corresponding to higher loneliness levels). This measure is highly associated with the UCLA loneliness scale (Nersesian et al., 2018). ...
Objectives
: Since there is limited knowledge with regard to the frequency and correlates of mild cognitive impairment and dementia among the oldest old based on large representative data (including institutionalized individuals), our objective was to fill this research gap.
Methods
: For our study, data came from the representative “Survey on quality of life and subjective well-being of the very old in North Rhine-Westphalia (NRW80+)”. This study included community-dwelling and institutionalized individuals aged 80 years and over (n=1,173, mean age: 86 years) residing in the most populous state of Germany (North Rhine-Westphalia). The DemTect was used to quantify cognitive impairment (i.e., probable mild cognitive impairment and probable dementia).
Results
: Overall, 73.1% of the individuals were not cognitively impaired, 17.0% of the individuals had probable mild cognitive impairment and 9.9% of the individuals had probable dementia. Compared to individuals without cognitive impairment, individuals with probable mild cognitive impairment were more likely to be male, live in an institutionalized setting, have a lower educational level, have a smaller network size, and have lower functional abilities. Moreover, compared to individuals without cognitive impairment, individuals with probable dementia were more likely to be older, live in an institutionalized setting, have a lower educational level, have a smaller network size, not be multimorbid, and have lower functional abilities.
Conclusions
: Our study identified several sociodemographic and health-related factors which are associated with probable mild cognitive impairment and probable dementia among the oldest old. This knowledge may help to address individuals at risk for mild cognitive impairment and dementia.
... Research that has examined the relationship between loneliness and physical health has found that somatic complaints, sleep disturbances (Cacioppo et al., 2002;Cacioppo et al., 2015), fatigue (Jaremka et al., 2014), poorer cardiovascular functioning (Cacioppo et al., 2002) and chronic illness (Petitte et al., 2015) have all been found to be associated with higher levels of loneliness. This relationship is potentially explained by lonely individuals exhibiting higher systemic inflammation biomarkers (see Nersesian et al., 2018). Similarly, loneliness has been associated with poor health behaviours (e.g., substance use, smoking, less exercise, poor nutrition) (Christiansen et al., 2016;Stickley et al., 2013). ...
In this chapter, we discuss two conceptualisations of loneliness: a singular construct and a multidimensional construct that can be experienced in both social and emotional forms. Based on these two views of loneliness, we discuss measurement approaches and difficulties capturing loneliness, which can be a highly subjective experience. We review two key theories that may help to explain how loneliness arises, is maintained and may be overcome. These are cognitive theories of loneliness and the social identity approach. The chapter goes on to highlight the significant physical and mental health implications of loneliness, including proposed mechanisms by which health affects loneliness and conversely how loneliness can affect health. Finally, we discuss research about the relationship between loneliness and various forms of psychopathology, including depression, anxiety, psychosis and substance use disorders. Empirical studies are reviewed throughout, and clinical implications of this evidence are highlighted.
... 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. ...
... Further, the 20-item UCLA scale has been adapted to a 3-item short form with strong evidence for validity (Hughes et al., 2004). In addition, the single self-report "lonely" item has been used as an index of loneliness in MIDUS (Nersesian et al., 2018), and the three items are well-correlated (.49 < r < .81, ps < .001). ...
Objective:
Loneliness represents a public health threat given its central role in predicting adverse mental and physical health outcomes. Prior research has established four of the Big Five personality traits as consistent cross-sectional predictors of loneliness in largely western, White samples. However, it is not clear if the personality predictors of loneliness vary across cultures.
Method:
The present study estimates associations between the Big Five traits and loneliness across distinct samples of White American, Black American, and Japanese adults (n = 6051 at T1). Confirmatory factor analysis and exploratory structural equation modeling were used to examine measurement invariance properties of the Big Five and loneliness across these groups. The factor structures were then carried forward to estimate associations between personality and loneliness across two assessments waves using structural equation modeling.
Results:
While Neuroticism was a strong predictor across groups, low Extraversion was more predictive of loneliness in Japan than in the U.S., and low Conscientiousness was only a significant predictor in the U.S.
Conclusions:
Previous literature offers a framework for interpreting these findings in that loneliness may be shaped comparatively more through interconnectedness in Japanese culture, while, in the U.S., individual goals and personal romantic expectations are more salient.
... and pain (Lee et al., 2019;Park et al., 2020;Santos-Orlandi et al., 2019). In addition, loneliness promotes inflammation and is correlated with increased synthesis of proinflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in adults exposed to acute stress (Jarmka, et al., 2013;Nersesian et al., 2018). Moreover, the association of loneliness and mortality has been well-documented; there is an estimated 26% and 29% increased likelihood of death for those reporting loneliness and social isolation, respectively (Holt-Lunstad et al., 2015). ...
Older adults are at an increased risk of loneliness. Many also serve as informal caregivers for persons with dementia and other disabling conditions, further predisposing them to loneliness. The primary objective was to assess current loneliness interventions for caregivers to inform development of effective therapies to improve their quality of life. An integrative review of the literature was conducted using five electronic databases and 12 studies were included for further analysis. Data were extracted regarding the type of intervention implemented, caregiver characteristics, and intervention effects. Five main intervention types emerged: mindful meditation, computer applications, music therapy, peer support, and community programs. Most care recipients had dementia, and most caregivers were spouses. Peer support was the most frequently utilized intervention, and common intervention strategies included providing emotional support, expanding one's social network, and supplying psychoeducational materials. Most interventions had methodological limitations and demonstrated small effect sizes. Hence, there remains a continued need for well-designed interventions that target loneliness in informal caregiver. Caregivers may benefit from interventions that expand their social network to improve their emotional regulation and understanding of their role. Further research on the role of group versus individual therapy is necessary to strengthen interventions and broaden their application.
... Personality characteristics, such as neuroticism, have been shown to increase the risk of loneliness and to moderate the risk of depression [9,10]. In addition, greater loneliness is associated with higher levels of Interleukin-6(IL-6), C-reactive protein (CRP) [11], and lower responsivity of cortisol [12]. Higher levels of Il-6, CRP, and dysregulation of the cortisol response are linked with cardiovascular disease and depression [13]. ...
Purpose
Loneliness is a subjective feeling by which an individual perceives a lack of closeness in interpersonal relationships. An isolated living status is linked with higher odds of risky health behavior. The conflicting impacts of loneliness and isolated living status on stress-related biomarkers, depressive symptoms, and disability remain unexplained.
Methods
Six hundred twenty-nine participants aged 66.0 (SD=7.3) separated into four groups: “Lonely and Isolated,” “Not Lonely, but Isolated,” “Lonely, but Not Isolated,” and “Neither Lonely, nor Isolated,” were retrieved from the Social Environment and Biomarkers of Aging Study conducted in 2000. Follow-up health indicators in 2006 included three stress-related biomarkers, depressive symptoms, and two physical disability indicators. A hierarchical regression was performed for the analysis.
Results
Firstly, compared to the “Neither Lonely nor Isolated” group, only the “Lonely, but Not Isolated” participants at baseline retained positive associations with the stress-related biomarkers levels 6 years later (urine cortisol level (B=9.25, 95% CI=3.24-15.27), serum Interleukin-6 level (B=2.76, 95% CI=0.72-4.79) and the serum high sensitivity C-reactive protein (hsCRP) level (B=0.40, 95% CI=0.17-0.62)). However, such associations were not observed in the “Lonely and Isolated” participants. Secondly, only “Lonely and Isolated” participants at baseline were positively associated with depressive symptoms 6 years later (B=1.70, 95% CI=0.11-3.30). Finally, the associations between combinations of loneliness and isolated living status and physical disability were eliminated after adjusting the covariables.
Conclusion
Four combinations of loneliness and isolated living status were associated with different impacts on stress-related biomarkers, depressive symptoms, and physical disability. Further dynamic investigations are warranted.
Background
Research suggests that systemic inflammation may link loneliness to adverse health outcomes, yet there is a gap in comprehensively reviewing recent evidence on the relationship between loneliness and biological measures of inflammation in adults. This scoping review synthesizes current research to address the question: Is there a definitive link between loneliness and biological markers of inflammation in adults?
Methods
Following the methods outlined by Arksey and O’Malley, we developed a protocol, defined our research question, and systematically searched PubMed, CINAHL, Embase, and Scopus for English-language studies conducted from 2018 to 2023 exploring the relationship between loneliness and biomarkers of inflammation in adults.
Results
Twelve studies meeting the inclusion criteria displayed heterogeneity in terms of sample characteristics, loneliness scales, and inflammatory biomarkers. The UCLA Loneliness Scale, in various forms, emerged as the predominant tool for measuring loneliness, while C-reactive protein and interleukin-6 were the most frequently evaluated inflammatory biomarkers. Notably, all 12 studies reported an association between loneliness and at least 1 biological marker of inflammation.
Conclusion
Research consistently associates loneliness with poor health outcomes in aging adults, but the underlying mechanisms remain unclear. This scoping review suggests that inflammation may serve as a pathway linking loneliness to adverse health outcomes. However, the variability across studies highlights the need for standardized measurement methods and a consideration of both the duration and extent of loneliness. Enhancing our understanding of how loneliness affects systemic inflammation may help clarify why loneliness is associated with negative health outcomes.
Objectives
To investigate the prevalence of loneliness among patients with IA with a specific focus on the associations with disease activity and impact.
Methods
We used data from a Danish cross-sectional survey comprising information on socio-demographics, mental health status, and social contacts among 12 713 patients with IA [rheumatoid arthritis (RA)/psoriatic arthritis (PsA)/axial spondylarthritis (axSpA)]. Data were linked to the DANBIO Rheumatology Registry and the National Patient Registry. Loneliness was measured by asking: ‘Are you ever alone, although you would prefer to be together with others?’. Association with disease activity and disease impact (Patient Global Assessment, pain, fatigue, physical function) was estimated using multivariable logistic regression [age, sex, cohabitation status, educational level, mental health status (depression, anxiety) and co-morbidity].
Results
: Approximately one-third reported loneliness. Prevalence was lowest for patients with RA [31.6% (95%CI: 30.5; 32.6)] compared with PsA and axSpA [36.0 (34.0; 38.0)] and [36.3 (34.1; 38.4), respectively]. It was highest among axSpA patients reporting high levels of depression [66.2% (60.0; 72.8)]. A positive association was observed between loneliness and disease activity. For disease impact, prevalence estimates were between 40% and 60% when patients experienced high levels of pain, fatigue, low levels of physical function, and high Patient Global Assessment.
Conclusions
Loneliness was highly prevalent in IA and associated with disease activity and impact. Therefore, loneliness is an important target for future mental health interventions in IA.
Background/Aims
Our current study aimed to investigate the determinants of dementia among the oldest old using longitudinal data from a representative sample covering both community-dwelling and institutionalized individuals.
Methods/Design
Longitudinal representative data were taken from the “Survey on quality of life and subjective well-being of the very old in North Rhine-Westphalia (NRW80+)” that surveyed community-dwelling and institutionalized individuals aged 80 years and above (n = 1,296 observations in the analytic sample), living in North Rhine-Westphalia (most populous state of Germany). The established DemTect was used to measure cognitive impairment (i.e., probable dementia). A logistic random effects model was used to examine the determinants of probable dementia.
Results
The mean age was 86.3 years (SD: 4.2 years). Multiple logistic regressions revealed that a higher likelihood of probable dementia was positively associated with lower education (e.g., low education compared to medium education: OR: 3.31 [95% CI: 1.10–9.98]), a smaller network size (OR: 0.87 [95% CI: 0.79–0.96]), lower health literacy (OR: 0.29 [95% CI: 0.14–0.60]), and higher functional impairment (OR: 13.45 [3.86–46.92]), whereas it was not significantly associated with sex, age, marital status, loneliness, and depressive symptoms in the total sample. Regressions stratified by sex were also reported.
Discussion
Our study identified factors associated with dementia among the oldest old. This study extends current knowledge by using data from the oldest old; and by presenting findings based on longitudinal, representative data (also including individuals residing in institutionalized settings).
Conclusions
Efforts to increase, among other things, formal education, network size, and health literacy may be fruitful in postponing dementia, particularly among older women. Developing health literacy programs, for example, may be beneficial to reduce the burden associated with dementia.
Objectives
Chronic loneliness is a widespread issue, and the gut-brain axis is known to be crucial in facilitating communication between the gut and brain. However, the precise mechanism by which chronic loneliness affects the gut-brain axis remains uncertain.
Methods
Fourteen 55-week-old Balb/c mice were used in the experiment, with seven mice being randomly assigned to the chronic social isolation (CSI) group. The CSI group mice underwent 12 weeks of isolation to simulate the psychiatric state of a population in prolonged social isolation. The mental state of the CSI mice was assessed through animal behavior analysis, while plasma cytokines were measured using ELISA. Additionally, the composition of the gut microbiota was analyzed using 16S rRNA sequencing, and the metabolite composition of the intestinal contents was examined using nontargeted metabolomics. The Student-T test was used to determine significant mean differences.
Results
Mice that were exposed to the CSI exhibited increased immobility time lengths in forced swimming and hanging tail experiments, and decreased movement lengths and number of times traversing the intermediate region, compared to control mice. Additionally, CSI decreased the abundance of the probiotics Ruminococcaceae, Akkermansiaceae, and Christensenellaceae. Additionally, CSI reduced the production of the metabolites oleamide and tryptophan. Furthermore, IL-1β, IL-4, and IL-6 were significantly increased, while TNF-α was significantly decreased.
Conclusion
CSI induces a dysbiotic gut microbiota and the production of neurorelated metabolites, which in turn increase inflammatory responses and result in depressive behaviors in CSI mice. Therefore, these findings suggest that the gut microbiota may serve as a target for the treatment of long-term social isolation-induced mental disorders.
Having associations with a range of adverse physical health outcomes including mortality, loneliness is increasingly recognized as a pressing public health concern, but the mechanisms studied to date do not yet explain all loneliness-related health risk. We sought to evaluate whether epigenetic influences on DNA methylation could help explain the relationship between loneliness and health. To do so, we first estimated associations between loneliness and epigenetic age acceleration (EAA) in a subsample of participants in the study of midlife in the United States (n = 1,310), before testing whether EAA mediated and/or moderated the association between loneliness and the onset of chronic health conditions in older adulthood (n = 445 completing longitudinal follow-ups). Greater loneliness was weakly associated with greater EAA in the Horvath, DunedinPACE, and GrimAge measures after accounting for demographic (0.08 ≤ β ≤ 0.11) and behavioral (0.06 ≤ β ≤ 0.08) covariates. Loneliness also predicted increases in chronic condition counts and these effects were more pronounced for individuals with higher DunedinPACE EAA values (interaction term β = 0.09, p = .009), suggesting possible synergistic impacts. EAA measures appear to be promising in helping to understand individual variations in the health impacts of loneliness, but the specific mechanisms involved require further research.
Objectives
Loneliness is considered a risk factor for cardiovascular diseases (CVD), but related evidence is mixed. Examining trajectories of loneliness over time, as compared to the assessment of loneliness at a single time point, can be useful to better understand the risks for CVD. The present study aimed to examine loneliness trajectories and their impacts on CVD in Chinese middle-aged and older adults.
Methods
The sample included 9235 adults aged 45 years and above from four waves of the China Health and Retirement Longitudinal Survey from 2011 to 2018. Loneliness was assessed by a single-item question with a four-point scale. CVD events were measured by self-reports of heart diseases and stroke in 2018.
Results
Group-based trajectory modeling showed that three loneliness trajectories emerged: stable low, moderate increasing, and high increasing loneliness. Binary logistic regression showed that loneliness trajectories were significantly associated with the risk of having CVD after controlling for all covariates. Specifically, compared to the group with stable low loneliness, people with moderate increasing had a higher risk of having stroke, and people with high increasing loneliness had higher risks of having both heart diseases and stroke. In contrast, loneliness at a single time point was not independently associated with the risk of having CVD.
Discussion
The present study identified groups of people vulnerable to CVD from the perspective of social connections in terms of loneliness trajectories. Middle-aged and older adults showing increasing loneliness may need social and emotional support to protect their cardiovascular health.
Abstract
Objectives
The article assesses the impact of loneliness and age on the mental health and cognitive functioning of individuals aged 45 and above in the Indian context. The mediating effect of marital status and age on the way loneliness impacts individuals’ cognition and mental health is examined.
Methods
Data were obtained from the pilot wave of Longitudinal Ageing Study in India, and scores of 1578 participants were considered for analysis. Standardised and validated measures were employed to measure loneliness, mental health and cognition of the participants. Multivariate analysis was employed to investigate the impact of loneliness and age on cognition and mental health. Structural equation modelling was used for evaluating the mediating effect of age and marital status.
Results
Loneliness significantly impacted mental health and global cognitive function, whereas age significantly impacted episodic memory and total cognition. Marital status had a significant mediating role on the impact of loneliness on individuals’ mental health and cognitive functioning.
Discussion
Fostering social support among lonely individuals might help mitigate loneliness, enhance their mental health status, and slow down cognitive decline.
Objectives
There are few studies investigating the determinants of psychosocial outcomes using data exclusively from the oldest old; and even fewer that use longitudinal data. Thus, our aim was to explore the determinants of psychosocial factors (in terms of life satisfaction, loneliness, and depressive symptoms) amongst the oldest old (also stratified by sex) based on representative, longitudinal data from Germany.
Methods/Design
Data from “Survey on quality of life and subjective well‐being of the very old in North Rhine‐Westphalia (NRW80+)” were used. This study includes community‐dwelling and institutionalized individuals aged 80 years and above (n = 1760 observations in the analytical sample) located in North Rhine‐Westphalia (the most populous state in Germany). The mean age was 86.6 years (SD: 4.3 years). Established instruments were used to quantify life satisfaction, loneliness, and depressive symptoms. Linear FE regressions were used in this study to mitigate the challenge of unobserved heterogeneity. Sex‐stratified regressions were also conducted. Results : Regressions showed that the loss of a spouse was significantly associated with worsening psychosocial factors (in terms of increases in depressive symptoms and loneliness). Furthermore, regressions revealed that increases in functional impairment were significantly associated with poorer psychosocial outcomes.
Conclusions
This longitudinal study enhanced our understanding of the factors contributing to poorer psychosocial outcomes among the oldest old. Efforts to avoid or postpone functional impairment may contribute to more favorable psychosocial outcomes. Moreover, our current study underlines the importance of spousal relationships for psychosocial outcomes in the oldest age group.
Objective
Aging is associated with increased pro-inflammatory gene expression and systemic inflammation, and psychosocial stress may accelerate these changes. Mindfulness interventions show promise for reducing psychosocial stress and extending healthspan. Inflammatory pathways may play a role. In a sample of lonely older adults, we tested whether mindfulness training reduces proinflammatory gene expression and protein markers of systemic inflammation.
Methods
Lonely older adults (65–85 years; N = 190) were randomly assigned to an 8-week Mindfulness-Based Stress Reduction (MBSR) or matched Health Enhancement Program (HEP). Blood was drawn pre- and post-intervention and at 3-month follow-up. In peripheral blood mononuclear cells (PBMCs), RNA profiling was used to assess transcriptional regulation by pro-inflammatory NF-kB as well as β-adrenergic CREB, antiviral IRF, and glucocorticoid receptor (GR) transcription factors. Plasma was assayed for proinflammatory markers IL-6 and CRP. Analyses tested time (pre, post, follow-up) by condition (MBSR versus HEP) effects.
Results
MBSR reduced NF-kB ( d = .17, p = .028) but did not alter CREB ( d = .10, p = .20), IRF ( d = .13, p = .086), or GR activity ( d = .14, p = .063) relative to HEP over time. Contrary to predictions, there were no time × condition effects of MBSR compared to HEP on reducing circulating IL-6 or CRP.
Conclusions
In lonely older adults, MBSR reduced cellular pro-inflammatory gene regulation in ways that would predict reduced disease risk. However, no similar effect was observed for circulating protein markers of inflammation. These results provide specificity about how mindfulness interventions may impact distinct inflammatory markers among aging adults in ways that may have important implications for healthspan.
Trial Registration
Clinical Trials identifier NCT02888600
The field of psychoneuroimmunology (PNI) examines interactions among psychological and behavioral states, the central autonomic nervous system, and the immune system and the implications of those interactions on mental and physical health. In this review, I consider the effects of stress on multiple levels of the the neuro-immune network in relation to the context of COVID-19 pandemic. In particular, I describe how stress influence the peripheral immune system, and how immune changes triggered by stress can influence the brain with effects on cognition, emotion, and behavior. I also consider how positive psychological states influence inflammatory processes that are closely related to physical and mental health, focusing on positive affect and eudaimonic well-being. I finish with a discussion of interventions that may be effective in improving immune function and mental and physical health.
Society within the Brain provides insightful accounts of scientific research linking social connection with brain and cognitive aging through state-of-the-art research. This involves comprehensive social network analysis, social neuroscience, neuropsychology, psychoneuroimmunology, and sociogenomics. This book provides a scientific discourse on how a society, community, or friends and family interact with individuals' cognitive aging. Issues concerning social isolation, rapidly increasing in modern societies, and the controversy in origins of individual difference in social brain and behaviour are discussed. An integrative framework is introduced to explicate how social networks and support alleviate the effects of aging in brain health and reduce dementia risks. This book is of interest and useful to a wide readership: from gerontologists, psychologists, clinical neuroscientists and sociologists, to those involved in developing community-based interventions or public health policy for brain health, to people interested in how social life influences brain aging or in the prevention of dementia.
Spousal bereavement is one of the most stressful experiences in adulthood. In a sample of 183 widow(er)s, bereaved about three months prior, we examined the intersection of employment, family income, and health outcomes (proinflammatory marker production, perceived stress, and grief symptoms). Bereaved employees had higher levels of monocyte-stimulated interleukin-6, tumor necrosis factor-α, chemokine ligands 4, and perceived stress than bereaved retirees. We also found an interaction such that family income was positively associated with perceived stress and grief symptoms for employed window(er)s, but not for retirees. These findings align with the reserve capacity model, which states that people at higher levels of socioeconomic status have more psychosocial resources to address psychosocial stressors. Employment likely served as an added psychological and inflammatory burden for all bereaved workers, except those with the highest incomes.
As a strong risk factor for mortality, individual differences in loneliness are of clear public health significance. Four of the Big Five traits have emerged as cross-sectional correlates, but the etiology of these links is unclear, as are relations with more specific personality facets. Thus, we estimated phenotypic, genetic, and environmental associations between loneliness and both broader and narrower personality dimensions. Traits that indexed Negative Emotionality (e.g., Neuroticism, Stress Reactivity, Alienation) and low Positive Emotionality (e.g., low Extraversion, low Well-Being) had the strongest associations with loneliness, though low Conscientiousness, low Agreeableness, and high Aggression were also implicated. These associations were explained by both genetic (0.30.<.|rg|.<.0.80) and unique environmental (0.10.<.|re|.<.0.35) influences, consistent with an etiology of loneliness involving several personality domains.
Given the important associations between couple conflict and various physical and mental health outcomes, it is essential to explore factors that may catalyze or exacerbate the frequency and impact of conflict in romantic relationships. One such factor may be relationship mindfulness, or the tendency to have a nonjudgmental awareness of one’s experiences in romantic relationships. Previous research has demonstrated a link between relationship mindfulness and various relational outcomes, but its association with relationship conflict has not yet been explored. Additionally, the current study sought to explore the mechanisms that link relationship mindfulness and relational outcomes. Based on previous research connecting conflict to negative partner attributions, the study examined how relationship mindfulness may predict conflict through negative partner attributions. Furthermore, the study aimed to incorporate loneliness as a potential mediator between relationship mindfulness and negative partner attributions. A sample of 116 different-sex middle-aged married couples were recruited to complete an online assessment. Using an actor–partner interdependence mediation model, the results indicated several significant associations among relationship mindfulness, negative partner attributions, loneliness, and relationship conflict. For example, a significant indirect effect was found; that is, female relationship mindfulness was associated with decreased relationship conflict via its prior association with both male loneliness and additionally through male loneliness and subsequent male negative partner attributions. The results indicate that by employing interventions that increase relationship mindfulness, it may be possible to both reduce loneliness and encourage more charitable partner attributions which, in turn, may reduce couple conflict.
Even before increased social isolation associated with the COVID-19 pandemic, 43% of adults aged 60 and older reported experiencing loneliness. Depression and loneliness often co-exist and are significant issues faced by middle-aged as well as older adults because each condition is likely to worsen health outcomes. This study of middle-aged and older adults examined how depression and loneliness affect diabetes (DM) control (A1C levels). This study is a secondary analysis of data from the Midlife in the United States Refresher (MIDUS-R) survey, a national survey of adults aged 25–74 years. Correlation analyses were conducted, and a hierarchical logistic regression was estimated to predict A1C levels ≤7% (recommended goal) or >7 using 1) demographics and physical health (ethnicity, gender, education, age, and comorbidities), 2) family and friend support, and 3) depression and loneliness. The sample of 92 participants with DM and A1C data from the MIDUS-R had mean age = 57.37, were 51% male, 68% non-Hispanic White; 39.1% had A1C >7. The average level of depression was low (CES-D mean 9.42) and loneliness was moderate (UCLA scale mean 12.43). Loneliness was correlated with A1C (r= .26, p< .05); depressive symptoms (r= .71, p< .001), family and friends support (r= −.36, r= −.38, respectively, both p< .001). Only loneliness significantly predicted higher A1C levels. People with higher levels of loneliness had increased odds of having A1C >7 (OR = 1.18, p < .05) after controlling for depression and all other variables. Loneliness had a greater impact than depression on A1C level among persons with DM. Healthcare providers should assess patients for loneliness as well as depression and reduce adverse health impacts by referring to psychosocial support as needed.
Social isolation is defined, in psychological terms, as the absence of meaningful social interactions, contacts, and relationships with family and friends, with neighbors. It can occur on an individual level and, on a broader level, within “society at large.” In the United States, three main groups of socially isolated individuals can be identified: people who reside in assisted-living facilities, nursing homes, or hospices, people suffering from “persistent loneliness” and people incarcerated in jails or prisons who are housed in involuntary solitary confinement. In this chapter, we discuss the psychological and neurobiological effects of isolation, using both animal models as well as direct studies of humans experiencing these conditions. Only by understanding the impact of isolation on the brain and the mechanisms that underlie these changes can we hope to develop interventions that prevent them from occurring in the first place. This knowledge may also contribute to the efforts of psychologists, clinicians, and community health leaders to employ evidence-based prevention programs to mitigate the risk of isolation-induced physical and psychological damage in humans.
Circulating levels of inflammatory biomarkers may be influenced by chronic psychological stressors such as those experienced by family caregivers. However, previous studies have found mostly small and inconsistent differences between caregivers and control samples on individual measures of systemic inflammation. Latent variables of inflammation were extracted from six biomarkers collected from two blood samples over 9 years apart for 502 participants in a national cohort study. One-half of these participants transitioned into a sustained family caregiving role between the blood samples. Two latent factors, termed “up-regulation” and “inhibitory feedback,” were identified, and the transition to family caregiving was associated with a lower increase over time on the inhibitory feedback factor indexed by interleukin (IL)-2 and IL-10. No caregiving effect was found on the up-regulation factor indexed primarily by IL-6 and C-reactive protein. These findings illustrate the advantages of using latent variable models to study inflammation in response to caregiving stress.
Rationale:
It has long been known that factors of the mind and of interpersonal relationships influence health, but it is only in the last 50 years that an independent scientific field of health psychology appeared, dedicated to understanding psychological and behavioral processes in health, illness, and healthcare.
Objective and method:
This article (a) reviews important research that answers the question of how human beings can have longer, happier lives; and (b) highlights trends in health psychology featuring articles in Social Science & Medicine as well as other related literature.
Results:
Since the 1970s, health psychology has embraced a biopsychosocial model such that biological factors interact and are affected by psychological and social elements. This model has illuminated all subjects of health, ranging from interventions to lower stress and/or to improve people's ability to cope with stressors, to mental and physical health. Importantly, a health psychology perspective is behavioral: The majority of chronic diseases of today can be avoided or reduced through healthy lifestyles (e.g., sufficient exercise, proper diet, sufficient sleep). Thus, behavior change is the key target to help reduce the immense public health burden of chronic lifestyle illnesses. Health psychology also focuses on how social patterns influence health behavior and outcomes, in the form of patient-provider interactions or as social forces in communities where people live, work, and play. Health psychology is congenial to other health sciences, especially when allied with ecological perspectives that incorporate factors upstream from individual behavior, such as networks linked to individuals (e.g., peer groups, communities). Over its history, health psychology research has been responsive to societal and medical needs and has routinely focused on understanding health disparities.
Conclusion:
By relying on a strong interdisciplinary approach, research in health psychology provides a remarkably comprehensive perspective on how people can live healthier lives.
Objectives: Loneliness is a biopsychosocial determinant of health and contributes to physical and psychological chronic illnesses, functional decline, and mortality in older adults. This paper presents the results of the first randomized trial of LISTEN, which is a new cognitive behavioral intervention for loneliness, on loneliness, neuroimmunological stress response, psychosocial functioning, quality of life, and measures of physical health.
Methods: The effectiveness of LISTEN was evaluated in a sample population comprising 27 lonely, chronically ill, older adults living in Appalachia. Participants were randomized into LISTEN or educational attention control groups. Outcome measures included salivary cortisol and DHEA, interleukin-6, interleukin-2, depressive symptoms, loneliness, perceived social support, functional ability, quality of life, fasting glucose, blood pressure, and body mass index.
Results: At 12 weeks after the last intervention session, participants of the LISTEN group reported reduced loneliness (p = 0.03), enhanced overall social support (p = 0.05), and decreased systolic blood pressure (p = 0.02). The attention control group reported decreased functional ability (p = 0.10) and reduced quality of life (p = 0.13).
Conclusions: LISTEN can effectively diminish loneliness and decrease the systolic blood pressure in community-dwelling, chronically ill, older adults. Results indicate that this population, if left with untreated loneliness, may experience functional impairment over a period as short as 4 months. Further studies on LISTEN are needed with larger samples, in varied populations, and over longer periods of time to assess the long-term effects of diminishing loneliness in multiple chronic conditions.
Purpose
The purpose of this study was to evaluate the effectiveness of LISTEN (Loneliness Intervention) on loneliness, depression, physical health, systemic inflammation, and genomic expression in a sample of lonely, chronically ill, older adults.
Methods
This was a prospective, longitudinal randomized trial of LISTEN, a novel intervention based on theories of narrative and cognitive restructuring to target specific aspects of loneliness. Twenty-three older, lonely, chronically ill adults were recruited from a family medicine clinic in West Virginia. Participants were randomized to two groups, 13 in LISTEN group (Loneliness Intervention) and 10 in attention control (healthy aging education). Participants attended an enrollment session where they completed consent, survey data (including sociodemographics and chronic illness diagnoses), baseline physical measures, and blood sampling for gene expression analysis. After completing the 5 weekly sessions, all participants attended a 12 week post data collection meeting (17 weeks post-baseline) for survey completion, physical measures and blood sampling.
Results
The results of this study show that the LISTEN intervention improves measures of physical and psychosocial health. Specifically, subjects enrolled in LISTEN showed reductions in systolic blood pressure, as well as decreased feelings of loneliness and depression. These changes may be due, in part, to a reduction in systemic inflammation, as measured by interleukin-2.
Conclusion
This study provides support for the use of LISTEN in reducing loneliness in chronically ill, older adults. Further, while some of our results are inconclusive, it provides rationale to expand our study population to evaluate the relationship between loneliness and systemic inflammation. In the future, enhancing knowledge about the relationships among loneliness, chronic illness, systemic inflammation, and gene expression of these particular targets, and how these relationships may change over time with intervention will inform translation of findings to clinical settings.
Objective:
Both objective and subjective aspects of social isolation have been associated with alterations in immune markers relevant to multiple chronic diseases among older adults. However, these associations may be confounded by health status, and it is unclear whether these social factors are associated with immune functioning among relatively healthy adults. The goal of this study was to examine the associations between perceived loneliness and circulating levels of inflammatory markers among a diverse sample of adults.
Methods:
Data come from a subset of the Multi-Ethnic Study of Atherosclerosis (n = 441). Loneliness was measured by three items derived from the UCLA Loneliness Scale. The association between loneliness and C-reactive protein (CRP) and fibrinogen was assessed using multivariable linear regression analyses. Models were adjusted for demographic and health characteristics.
Results:
Approximately 50% of participants reported that they hardly ever felt lonely and 17.2% felt highly lonely. Individuals who were unmarried/unpartnered or with higher depressive symptoms were more likely to report being highly lonely. There was no relationship between perceived loneliness and ln(CRP) (β = -0.051, p = 0.239) adjusting for demographic and health characteristics. Loneliness was inversely associated with ln(fibrinogen) (β = -0.091, p = 0.040), although the absolute magnitude of this relationship was small.
Conclusion:
These results indicate that loneliness is not positively associated with fibrinogen or CRP among relatively healthy middle-aged adults.
A recent meta-analysis has shown that loneliness and social isolation are risk factors for coronary heart disease and stroke.1 These latest findings, specific to cardiovascular outcomes, are consistent with substantial research indicating broad health risks (eg, immune functioning, cardiovascular functioning, cognitive decline) associated with the quantity and quality of social relationships—including several meta-analyses documenting mortality risk.2 ,3 In the most comprehensive of these,3 the overall odds for mortality was 1.50, similar to the risk from light smoking and exceeding the risks conferred by hypertension and obesity. Thus, the epidemiological data suggest that having more and better quality social relationships is linked to decreased health risks and having fewer and poorer quality relationships increased risk.2 ,3
Research has also documented the influence of social connections (including measures specific to loneliness and isolation) on multiple pathways involved in both the development and progression of coronary heart disease and stroke. As depicted in figure 1, these include lifestyle (eg, nutrition, physical activity, sleep),4 treatment adherence and cooperation,5 and direct effects on surrogate biological markers.6 ,7 Recent longitudinal data from four nationally representative US samples revealed a dose–response effect of social integration on several surrogate biomarkers of cardiovascular disease including hypertension, body mass index, waist circumference and inflammation (hs-CRP).6 Moreover, most epidemiological studies control for lifestyle factors (eg, smoking, physical activity), documenting an independent influence of social relationships on mortality. Taken together, these latest findings specific to loneliness and isolation1 bolster the already robust evidence documenting that social connections significantly predict morbidity and mortality, supporting the case for inclusion as a risk factor for cardiovascular disease (CVD).
Figure 1
Simplified model of possible direct and indirect pathways by which social connections influence disease morbidity and mortality.
How should these data inform clinical practice? …
Background The influence of social relationships on morbidity is widely accepted, but the size of the risk to cardiovascular health is unclear.
Objective We undertook a systematic review and meta-analysis to investigate the association between loneliness or social isolation and incident coronary heart disease (CHD) and stroke.
Methods Sixteen electronic databases were systematically searched for longitudinal studies set in high-income countries and published up until May 2015. Two independent reviewers screened studies for inclusion and extracted data. We assessed quality using a component approach and pooled data for analysis using random effects models.
Results Of the 35 925 records retrieved, 23 papers met inclusion criteria for the narrative review. They reported data from 16 longitudinal datasets, for a total of 4628 CHD and 3002 stroke events recorded over follow-up periods ranging from 3 to 21 years. Reports of 11 CHD studies and 8 stroke studies provided data suitable for meta-analysis. Poor social relationships were associated with a 29% increase in risk of incident CHD (pooled relative risk: 1.29, 95% CI 1.04 to 1.59) and a 32% increase in risk of stroke (pooled relative risk: 1.32, 95% CI 1.04 to 1.68). Subgroup analyses did not identify any differences by gender.
Conclusions Our findings suggest that deficiencies in social relationships are associated with an increased risk of developing CHD and stroke. Future studies are needed to investigate whether interventions targeting loneliness and social isolation can help to prevent two of the leading causes of death and disability in high-income countries.
Study registration number CRD42014010225.
Significance
Perceived social isolation (PSI) (loneliness) is linked to increased risk of chronic disease and mortality, and previous research has implicated up-regulated inflammation and down-regulated antiviral gene expression (the conserved transcriptional response to adversity; CTRA) as a potential mechanism for such effects. The present studies used integrative analyses of transcriptome regulation in high-PSI humans and rhesus macaques to define the basis for such effects in neuroendocrine-related alterations in myeloid immune cell population dynamics. CTRA up-regulation also preceded increases in PSI, suggesting a reciprocal mechanism by which CTRA gene expression may both propagate PSI and contribute to its related disease risks.
Background:
Research supports an association between smoking and negative affect. Loneliness is a negative affective state experienced when a person perceives themselves as socially isolated and is associated with poor health behaviors and increased morbidity and early mortality.
Objectives:
In this article, we systematically review the literature on loneliness and smoking and suggest potential theoretical and methodological implications.
Methods:
PubMed and PsycINFO were systematically searched for articles that assessed the statistical association between loneliness and smoking. Articles that met study inclusion criteria were reviewed.
Results:
Twenty-five studies met inclusion criteria. Ten studies were conducted with nationally representative samples. Twelve studies assessed loneliness using a version of the UCLA Loneliness Scale and nine used a one-item measure of loneliness. Seventeen studies assessed smoking with a binary smoking status variable. Fourteen of the studies were conducted with adults and 11 with adolescents. Half of the reviewed studies reported a statistically significant association between loneliness and smoking. Of the studies with significant results, all but one study found that higher loneliness scores were associated with being a smoker. Conclusions/Importance: Loneliness and smoking are likely associated, however, half of the studies reviewed did not report significant associations. Studies conducted with larger sample sizes, such as those that used nationally representative samples, were more likely to have statistically significant findings. Future studies should focus on using large, longitudinal cohorts, using measures that capture different aspects of loneliness and smoking, and exploring mediators and moderators of the association between loneliness and smoking.
Interleukin-6 and C-reactive protein are commonly assessed biomarkers linked to illness, obesity, and stressful life events. However, relatively little is known about their heritability. By comparing Caucasian twins from the Midlife in the US project (MIDUS), we estimated the heritability of IL-6, its soluble receptor, and CRP. Based on the hypothesis that adiposity might contribute more to IL-6 than to sIL-6r, we fit heritability models quantifying the extent to which each reflected genetic and environmental factors shared with obesity. Genetic influences on IL-6 and its receptor proved to be distinct. Further, the appearance of a heritable basis for IL-6 was mediated largely via shared paths with obesity. Supporting this conclusion, we confirmed that when unrelated adult controls are carefully matched to twin participants on BMI, age, gender and socioeconomic indices, their IL-6 is similar to the corresponding twins. In contrast, the effect of BMI on CRP was split between shared genetics and environmental influences. In conclusion, IL-6 is strongly affected by factors associated with obesity accounting for its lability and responsiveness to diet, life style and contemporaneous events.
Copyright © 2015. Published by Elsevier Inc.
Sociality permeates each of the fundamental motives of human existence and plays a critical role in evolutionary fitness across the lifespan. Evidence for this thesis draws from research linking deficits in social relationship-as indexed by perceived social isolation (i.e. loneliness)-with adverse health and fitness consequences at each developmental stage of life. Outcomes include depression, poor sleep quality, impaired executive function, accelerated cognitive decline, unfavourable cardiovascular function, impaired immunity, altered hypothalamic pituitary-adrenocortical activity, a pro-inflammatory gene expression profile and earlier mortality. Gaps in this research are summarized with suggestions for future research. In addition, we argue that a better understanding of naturally occurring variation in loneliness, and its physiological and psychological underpinnings, in non-human species may be a valuable direction to better understand the persistence of a 'lonely' phenotype in social species, and its consequences for health and fitness.
© 2015 The Author(s) Published by the Royal Society. All rights reserved.
Actual and perceived social isolation are both associated with increased risk for early mortality. In this meta-analytic review, our objective is to establish the overall and relative magnitude of social isolation and loneliness and to examine possible moderators. We conducted a literature search of studies (January 1980 to February 2014) using MEDLINE, CINAHL, PsycINFO, Social Work Abstracts, and Google Scholar. The included studies provided quantitative data on mortality as affected by loneliness, social isolation, or living alone. Across studies in which several possible confounds were statistically controlled for, the weighted average effect sizes were as follows: social isolation odds ratio (OR) = 1.29, loneliness OR = 1.26, and living alone OR = 1.32, corresponding to an average of 29%, 26%, and 32% increased likelihood of mortality, respectively. We found no differences between measures of objective and subjective social isolation. Results remain consistent across gender, length of follow-up, and world region, but initial health status has an influence on the findings. Results also differ across participant age, with social deficits being more predictive of death in samples with an average age younger than 65 years. Overall, the influence of both objective and subjective social isolation on risk for mortality is comparable with well-established risk factors for mortality.
© The Author(s) 2015.
Objective:
Social relationships are widely understood to be important for sustaining and improving health and longevity, but it remains unclear how different dimensions of social relationships operate through similar or distinct mechanisms to affect biophysiological markers of aging-related disease over time.
Method:
This study utilized longitudinal data on a nationally representative sample of older adults from the National Social Life, Health, and Aging Project (2005-2011) to examine the prospective associations between social integration and social support and change in systolic blood pressure (SBP) and hypertension risk over time.
Results:
Although both social relationship dimensions have significant physiological impacts, their relative importance differs by outcome. Low social support was predictive of increase in SBP, whereas low social integration was predictive of increase in risk of hypertension.
Discussion:
The different roles of relationship characteristics in predicting change in physiological outcomes suggest specific biophysiological stress response and behavioral mechanisms that have important implications for both scientific understandings and effective prevention and control of a leading chronic condition in late life.
Midlife in the United States (MIDUS) is a national longitudinal study of health and well-being (http://midus.wisc.edu/). It was conceived by a multidisciplinary team of scholars interested in understanding aging as an integrated bio-psycho-social process, and as such it includes data collected in a wide array of research protocols using a variety of survey and non-survey instruments. The data captured by these different protocols (comprising around 20,000 variables) represent survey measures, cognitive assessments, daily stress diaries, clinical, biomarker and neuroscience data which are contained in separate flat or stacked data files with a common ID system that allows easy data merges among them. All MIDUS datasets and documentation are archived at the ICPSR (http://www.icpsr.umich.edu/) repository at the University of Michigan and are publicly available in a variety of formats and statistical packages. Special attention is given to providing clear user-friendly documentation; the study has embraced the Data Documentation Initiative (DDI) metadata standard and produces DDI-Lifecycle compliant codebooks. Potential for secondary use of MIDUS is high and actively encouraged. The study has become very popular with the research public as measured by data downloads and citation counts (see Reuse Potential below).
Objective:
The objective of this study was to test a conceptual model of loneliness in which social structural factors are posited to operate through proximal factors to influence perceptions of relationship quality and loneliness.
Methods:
We used a population-based sample of 225 White, Black, and Hispanic men and women aged 50 through 68 from the Chicago Health, Aging, and Social Relations Study to examine the extent to which associations between sociodemographic factors and loneliness were explained by socioeconomic status, physical health, social roles, stress exposure, and, ultimately, by network size and subjective relationship quality.
Result:
Education and income were negatively associated with loneliness and explained racial/ethnic differences in loneliness. Being married largely explained the association between income and loneliness, with positive marital relationships offering the greatest degree of protection against loneliness. Independent risk factors for loneliness included male gender, physical health symptoms, chronic work and/or social stress, small social network, lack of a spousal confidant, and poor-quality social relationships.
Discussion:
Longitudinal research is needed to evaluate the causal role of social structural and proximal factors in explaining changes in loneliness.
Earlier studies on gender differences in loneliness appear to have produced contradictory results. However, when 39 existing data sets were classified according to whether they used the UCLA scale (N = 28) or a self-labeling measure (N = II) of loneliness, the results revealed a clear pattern. Statistically significant sex differences are not usually found with the UCLA scale, but, when they are found, males typically have higher loneliness scores. In terms of self-labeling, women more frequently than men admit being lonely. Sex role factors may help explain these seemingly contradictory results. Of the various possible explanations of the gender differences in self-labeled loneliness, most assume that social influence processes play a crucial role. To test this viewpoint, an experiment was conducted. Subjects (N = 117) were presented with a case history of a lonely person, which varied only the target person's sex. The subjects were more rejecting of a lonely male than of a lonely female. These results support the view that women are more apt to acknowledge their loneliness than men because the negative consequences of admitting loneliness are less for women.
Objective:
Pain, depression, and fatigue function as a symptom cluster and thus may share common risk factors. Interpersonal relationships clearly influence health, suggesting that loneliness may promote the development of the pain, depression, and fatigue symptom cluster. We hypothesized that loneliness would be related to concurrent symptom cluster levels and increases in symptom cluster levels over time.
Method:
We utilized two observational studies with distinct longitudinal samples. Study 1 was a sample of cancer survivors and benign controls (N = 115) assessed annually for 2 years. Study 2 was a sample of older adults caring for a spouse with dementia (caregivers) and non-caregiver controls (N = 229) assessed annually for 4 years. Participants completed annual measures assessing loneliness, pain, depression, and fatigue.
Results:
Across both samples, lonelier participants experienced more concurrent pain, depression, and fatigue and larger increases in symptom cluster levels from one year to the next than less lonely participants. Sleep quality did not mediate the results in either study. All analyses were adjusted for relevant demographic and health variables.
Conclusions:
Two longitudinal studies with different populations demonstrated that loneliness was a risk factor for the development of the pain, depression, and fatigue symptom cluster over time. The current research helps identify people most at risk for pain, depression, and fatigue, and lays the groundwork for research about their diagnosis and treatment. These data also highlight the health risks of loneliness; pain, depression, and fatigue often accompany serious illness and place people at risk for poor health and mortality.
Background:
Known risk factors for Alzheimer's disease and other dementias include medical conditions, genetic vulnerability, depression, demographic factors and mild cognitive impairment. The role of feelings of loneliness and social isolation in dementia is less well understood, and prospective studies including these risk factors are scarce.
Methods:
We tested the association between social isolation (living alone, unmarried, without social support), feelings of loneliness and incident dementia in a cohort study among 2173 non-demented community-living older persons. Participants were followed for 3 years when a diagnosis of dementia was assessed (Geriatric Mental State (GMS) Automated Geriatric Examination for Computer Assisted Taxonomy (AGECAT)). Logistic regression analysis was used to examine the association between social isolation and feelings of loneliness and the risk of dementia, controlling for sociodemographic factors, medical conditions, depression, cognitive functioning and functional status.
Results:
After adjustment for other risk factors, older persons with feelings of loneliness were more likely to develop dementia (OR 1.64, 95% CI 1.05 to 2.56) than people without such feelings. Social isolation was not associated with a higher dementia risk in multivariate analysis.
Conclusions:
Feeling lonely rather than being alone is associated with an increased risk of clinical dementia in later life and can be considered a major risk factor that, independently of vascular disease, depression and other confounding factors, deserves clinical attention. Feelings of loneliness may signal a prodromal stage of dementia. A better understanding of the background of feeling lonely may help us to identify vulnerable persons and develop interventions to improve outcome in older persons at risk of dementia.
Aging results in chronic low grade inflammation that is associated with increased risk for disease, poor physical functioning and mortality. Strategies that reduce age-related inflammation may improve the quality of life in older adults. Regular exercise is recommended for older people for a variety of reasons including increasing muscle mass and reducing risk for chronic diseases of the heart and metabolic systems. Only recently has exercise been examined in the context of inflammation. This review will highlight key randomized clinical trial evidence regarding the influence of exercise training on inflammatory biomarkers in the elderly. Potential mechanisms will be presented that might explain why exercise may exert an anti-inflammatory effect.
A number of mechanisms have been proposed through which social isolation and loneliness may affect health, including health-related behavioral and biological factors. However, it is unclear to what extent isolation and loneliness are independently associated with these pathways. The objective of the present analysis was to determine the impact of social isolation and loneliness, individually as well as simultaneously, on health-related behavioral and biological factors using data from the English Longitudinal Study of Ageing (ELSA).
Data on health behaviors (smoking and physical activity) were analyzed from 8,688 participants and data on blood pressure, cholesterol, and inflammatory markers were analyzed from over 5,000 of these participants who were eligible for a nurse visit and blood sampling. Loneliness was measured using the short form of the Revised UCLA scale and an index of social isolation was computed incorporating marital status; frequency of contact with friends, family, and children; and participation in social activities.
Fewer than 2% of participants reported being lonely all the time, while nearly 7% had the highest possible scores on social isolation. Both social isolation and loneliness were associated with a greater risk of being inactive, smoking, as well as reporting multiple health-risk behaviors. Social isolation was also positively associated with blood pressure, C-reactive protein, and fibrinogen levels.
Loneliness and social isolation may affect health independently through their effects on health behaviors. In addition, social isolation may also affect health through biological processes associated with the development of cardiovascular disease.
This study evaluated the association between loneliness and the metabolic syndrome, which refers to a clustering of factors that have been shown to increase risk for cardiovascular disease, diabetes, stroke, and mortality. A secondary purpose was to evaluate whether age moderated the association between loneliness and the metabolic syndrome.
Participants were 52 to 79 years old, and they were drawn from a population-based survey of people 50 years of age and older living in England (N = 3211). They completed a self-report measure of loneliness and a nurse visit that included collection of blood pressure, blood sample, and anthropometric measures.
Self-reported loneliness and the metabolic syndrome.
After controlling for demographic variables and smoking status, loneliness was significantly associated with increasing likelihood of meeting criteria for the metabolic syndrome and with the individual criterion of central obesity. The association between loneliness and the metabolic syndrome was not moderated by age.
Results suggest that loneliness is associated with the metabolic syndrome. Therefore, the metabolic syndrome may be among the pathways by which loneliness increases risk of morbidity and mortality.
Social and demographic trends are placing an increasing number of adults at risk for loneliness, an established risk factor for physical and mental illness. The growing costs of loneliness have led to a number of loneliness reduction interventions. Qualitative reviews have identified four primary intervention strategies: (a) improving social skills, (b) enhancing social support, (c) increasing opportunities for social contact, and (d) addressing maladaptive social cognition. An integrative meta-analysis of loneliness reduction interventions was conducted to quantify the effects of each strategy and to examine the potential role of moderator variables. Results revealed that single-group pre-post and nonrandomized comparison studies yielded larger mean effect sizes relative to randomized comparison studies. Among studies that used the latter design, the most successful interventions addressed maladaptive social cognition. This is consistent with current theories regarding loneliness and its etiology. Theoretical and methodological issues associated with designing new loneliness reduction interventions are discussed.
Background:
Reduction of premature mortality is a UN Sustainable Development Goal. Unlike other high-income countries, age-adjusted mortality in the USA plateaued in 2010 and increased slightly in 2015, possibly because of rising premature mortality. We aimed to analyse trends in mortality in the USA between 1999 and 2014 in people aged 25-64 years by age group, sex, and race and ethnicity, and to identify specific causes of death underlying the temporal trends.
Methods:
For this analysis, we used cause-of-death and demographic data from death certificates from the US National Center for Health Statistics, and population estimates from the US Census Bureau. We estimated annual percentage changes in mortality using age-period-cohort models. Age-standardised excess deaths were estimated for 2000 to 2014 as observed deaths minus expected deaths (estimated from 1999 mortality rates).
Findings:
Between 1999 and 2014, premature mortality increased in white individuals and in American Indians and Alaska Natives. Increases were highest in women and those aged 25-30 years. Among 30-year-olds, annual mortality increases were 2·3% (95% CI 2·1-2·4) for white women, 0·6% (0·5-0·7) for white men, and 4·3% (3·5-5·0) and 1·9% (1·3-2·5), respectively, for American Indian and Alaska Native women and men. These increases were mainly attributable to accidental deaths (primarily drug poisonings), chronic liver disease and cirrhosis, and suicide. Among individuals aged 25-49 years, an estimated 111 000 excess premature deaths occurred in white individuals and 6600 in American Indians and Alaska Natives during 2000-14. By contrast, premature mortality decreased substantially across all age groups in Hispanic individuals (up to 3·2% per year), black individuals (up to 3·9% per year), and Asians and Pacific Islanders (up to 2·6% per year), mainly because of declines in HIV, cancer, and heart disease deaths, resulting in an estimated 112 000 fewer deaths in Hispanic individuals, 311 000 fewer deaths in black individuals, and 34 000 fewer deaths in Asians and Pacific Islanders aged 25-64 years. During 2011-14, American Indians and Alaska Natives had the highest premature mortality, followed by black individuals.
Interpretation:
Important public health successes, including HIV treatment and smoking cessation, have contributed to declining premature mortality in Hispanic individuals, black individuals, and Asians and Pacific Islanders. However, this progress has largely been negated in young and middle-aged (25-49 years) white individuals, and American Indians and Alaska Natives, primarily because of potentially avoidable causes such as drug poisonings, suicide, and chronic liver disease and cirrhosis. The magnitude of annual mortality increases in the USA is extremely unusual in high-income countries, and a rapid public health response is needed to avert further premature deaths.
Funding:
US National Cancer Institute Intramural Research Program.
Each year, the American Heart Association (AHA), in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together the most up-to-date statistics related to heart disease, stroke, and other cardiovascular and metabolic diseases and presents them in its Heart Disease and Stroke Statistical Update. The Statistical Update represents a critical resource for the lay public, policy makers, media professionals, clinicians, healthcare administrators, researchers, and others seeking the best available data on these conditions. Together, cardiovascular disease (CVD) and stroke produce immense health and economic burdens in the United States and globally. The Statistical Update brings together in a single document up-to-date information on the core health behaviors and health factors that define cardiovascular health; a range of major clinical disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, …
There is a strong association between elevated plasma Lp(a) concentrations and increased incidence of cardiovascular disease. The aim of the study was to investigate Lp(a) levels in obesity before and after weight reduction. Obese but otherwise healthy patients with weight problems were studied. Four hundred seventy-six female patients (40.3±13.3 years, body mass index 38.8 kg/m2) and 152 male patients (41.1±12.7 years, body mass index 40.7kg/m2) were examined after overnight fasting. One handred and four of these patients (76 female, 28 male) were studied after long-term dieting (1200 kcal/day: 20% protein, 30% fat and 50% carbohydrates). After 7.3±5.4 months the mean weight loss was 14.2±10.5 kg, and blood pressure, triglycerides, blood glucose and uric acid had declined. Lp(a) concentrations decreased in patients with high Lp(a) levels. The decrease in Lp(a) level was correlated with weight loss. The correlation persisted even after removing the linear effects of initial Lp(a) concentrations and all other variables measured. Lp(a) level did not correlate with either body mass index, waist circumference, or the ratio of waist circumference to hip circumference. Also, an inverse relationship between TG and Lp(a) was observed. High Lp(a) concentrations are reduced by weight reduction. The underlying mechanisms are not known. The association of Lp(a) reduction with weight loss may be due to a low calorie diet rich in unsaturated fatty acids.
Increasing evidence suggests that perceived social isolation or loneliness is a major risk factor for physical and mental illness in later life. This review assesses the status of research on loneliness and health in older adults. Key concepts and definitions of loneliness are identified, and the prevalence, correlates, and health effects of loneliness in older individuals are reviewed. Theoretical mechanisms that underlie the association between loneliness and health are also described, and illustrative studies examining these mechanisms are summarized. Intervention approaches to reduce loneliness in old age are highlighted, and priority recommendations for future research are presented.
Significance
Midlife increases in suicides and drug poisonings have been previously noted. However, that these upward trends were persistent and large enough to drive up all-cause midlife mortality has, to our knowledge, been overlooked. If the white mortality rate for ages 45−54 had held at their 1998 value, 96,000 deaths would have been avoided from 1999–2013, 7,000 in 2013 alone. If it had continued to decline at its previous (1979‒1998) rate, half a million deaths would have been avoided in the period 1999‒2013, comparable to lives lost in the US AIDS epidemic through mid-2015. Concurrent declines in self-reported health, mental health, and ability to work, increased reports of pain, and deteriorating measures of liver function all point to increasing midlife distress.
Background:
Older persons are particularly vulnerable to loneliness because of common age-related changes and losses. This paper reviews predictors of loneliness in the older population as described in the current literature and a small qualitative study.
Methods:
Peer-reviewed journal articles were identified from psycINFO, MEDLINE, and Google Scholar from 2000–2012. Overall, 38 articles were reviewed. Two focus groups were conducted asking older participants about the causes of loneliness.
Results:
Variables significantly associated with loneliness in older adults were: female gender, non-married status, older age, poor income, lower educational level, living alone, low quality of social relationships, poor self-reported health, and poor functional status. Psychological attributes associated with loneliness included poor mental health, low self-efficacy beliefs, negative life events, and cognitive deficits. These associations were mainly studied in cross-sectional studies. In the focus groups, participants mentioned environmental barriers, unsafe neighborhoods, migration patterns, inaccessible housing, and inadequate resources for socializing. Other issues raised in the focus groups were the relationship between loneliness and boredom and inactivity, the role of recent losses of family and friends, as well as mental health issues, such as shame and fear.
Conclusions:
Future quantitative studies are needed to examine the impact of physical and social environments on loneliness in this population. It is important to better map the multiple factors and ways by which they impact loneliness to develop better solutions for public policy, city, and environme