Loneliness in middle-aged men increased the risk of them developing cancer by 10%

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A recent study by the University of Eastern Finland shows that loneliness among middle-aged men is associated with an increased risk of cancer.

According to the researchers, taking account of loneliness and social relationships should thus be an important part of comprehensive health care and disease prevention. The findings were published in Psychiatry Research.

“It has been estimated, on the basis of studies carried out in recent years, that loneliness could be as significant a health risk as smoking or overweight. Our findings support the idea that attention should be paid to this issue,” Project Researcher Siiri-Liisi Kraav from the University of Eastern Finland says.

The study was launched in the 1980s with 2,570 middle-aged men from eastern Finland participating. Their health and mortality have been monitored on the basis of registered data up until the present day. During the follow-up, 649 men, i.e. 25% of the participants, developed cancer, and 283 men (11%) died of cancer.

Loneliness increased the risk of cancer by about ten percent.

This association with the risk of cancer was observed regardless of age, socio-economic status, lifestyle, sleep quality, depression symptoms, body mass index, heart disease and their risk factors. In addition, cancer mortality was higher in cancer patients who were unmarried, widowed or divorced at baseline.

“Awareness of the health effects of loneliness is constantly increasing. Therefore, it is important to examine, in more detail, the mechanisms by which loneliness causes adverse health effects. This information would enable us to better alleviate loneliness and the harm caused by it, as well as to find optimal ways to target preventive measures.”


Loneliness is a multidimensional and complex construct

There are more and more elderly people living alone, and some of them are at risk of feeling lonely or socially isolated (1-2), although – as we shall see – loneliness and isolation are two different issues: a person can be alone and not feel alone and vice versa. Weiss (3) affirms that loneliness is a natural phenomenon, a (personal) feeling that may arise at certain moments in life and affect anyone, regardless of gender, age or other socio-demographic characteristics.

He also explains that loneliness is often seen as rooted in weakness or self-pity, as something that – supposedly – the individual should be able to eliminate, since it is not a physical ailment. Furthermore, he makes the distinction between emotional loneliness and social loneliness. Other authors have defined loneliness from different perspectives: as a negative psychological response to a discrepancy between the social relationships one desires (expectations) and the relationships one actually has (objective, real ones); as an individual feeling characterized by an unpleasant or inadmissible lack of quality in certain social relationships that can occur either because one has fewer social contacts than one wishes to have, or because the level of intimacy hoped for in relationships is not there; as the subjective component of the objective measure of social isolation, in other words, loneliness would be the inverse of a situation of social support; as a social pain, something comparable to physical pain, because if physical pain arises to protect us from physical dangers, loneliness would manifest itself as a way to protect us from the danger of remaining isolated (related to the importance of social connections); etc.

In general, it is assumed that emotional loneliness refers to the absence of an attachment figure (together with feelings of isolation) and social loneliness as the lack of a social network, the absence of a circle of people that allows an individual to develop a sense of belonging, of company, of being part of a community.

Both in daily life and in the research area, various researchers have referred to “loneliness” and “social isolation” indistinctly. Others, however, find both terms very different from each other. Making accurate evaluations depends on a clear definition of the concept of loneliness, with special awareness of its multidimensionality and its differences with respect to related concepts (social isolations or a lack of social support).

Loneliness and isolation place people at risk of vulnerability or social frailty; this dynamic concept of scarcity is closely linked to sustainability, development, social exclusion, poverty, and the lack of social support resources. Furthermore, social vulnerability is closely tied to physical frailty and mortality.

When evaluating loneliness, and considering the previous perspectives, some researchers have used a single question, taken from the CES-D (‘I feel lonely’), or a single item, for example, ‘Do you feel lonely?’ (4); ‘Do you suffer from loneliness?’ (5); and ‘Are you ever bothered by feelings of loneliness?’ (6-13), which is used only to measure the feeling of loneliness; meanwhile, others have used scales such as the UCLA Loneliness Scale (UCLA) (14-21) or the Jong Gierveld Loneliness Scale (dJGLS) (22-25), which are based on a more multidimensional perspective. The dJGLS scale, widely used in Europe and less in the Anglo-Saxon countries, is an eleven-item scale that combines both social and emotional loneliness, reflecting the more complex perspective mentioned above.

However you look at it, loneliness, that sense of lacking or privation, exerts a powerful influence over our health. There are multiple facets to loneliness: there are feelings of emptiness or abandonment associated with a lack of relationships or intimacy; there is the temporal perspective, (loneliness sets in over time) through which the individual perceives his or her own loneliness; there is the set of emotional aspects that accompany loneliness, including sadness, melancholy, frustration, shame or desperation; and, there is the individual’s own subjective evaluation regarding the quality and quantity of his or her social relationships, built and rebuilt by the people in their lives, an evaluation which depends on the continuous interaction between factors which are rather diverse (identity, personality, expectations, life events, interpersonal engagement, socio-economic variables, household, etc.). Yet, despite all of this, while effective interventions are necessary, they are still scarce.

Loneliness and health

Health determinants can be divided into intrinsic (medical conditions and genetics, frailty, etc.) and extrinsic (physical and social environment), which, in turn, interact with each other, creating anomalous and bidirectional synergies. We note that some of these are social determinants, such as socioeconomic level (level of education, occupation, income, and social vulnerability), social relationships and support from family and friends.

These factors have been linked to an increased risk of mortality (26). Our health and development are marked by our involvement in community social activities, our ability to take care of ourselves, our level of control over the circumstances of our lives, and by the context in which our relationship with the neighborhood, community and society takes place. Usually, most of these factors tend to be grouped under the concept of social vulnerability, which is calculated in a manner similar to the frailty index, that is, as a sum of deficits that can be measured and quantified (27). This social vulnerability has been associated with a higher prevalence of frailty and higher levels of hospital mortality (28-32).

The deficits linked to social vulnerability should not be considered apart; rather, they should be understood as an accumulation of deficiencies that provoke changes at the cellular and tissue level. Loneliness can contribute to alterations in cellular function, to an increase in vascular resistance (33) and to an increase in the incidence of specific diseases such as depression (14), cognitive deterioration and the progression of Alzheimer’s disease (34), obesity (35), stroke and hypertension (36), many of which are mediated by an alteration in vascular resistance, an increase in sympathetic-adrenergic activity stimulated by an increase in the activity of the hypothalamic-pituitary-adrenal axis (HPA) (37), due to immune changes and to an increase in inflammatory activity mediated by the action of glucocorticoids and proinflammatory factors that increase leukocyte and lymphocyte activity (38).

This increased state of vulnerability mediated by inflammatory activity, the changes in the immune system and neuromuscular system and the influence, in turn, by social factors (socioeconomic level, level of education, abuse or mistreatment, life partner, social networks and neighborhood) have not been studied as much as biological or clinical factors. We note that the definition of frailty syndrome has moved away from a purely physical criteria and has approached a more integral consideration of the individual, one that includes psychosocial criteria; in fact, a multidimensional origin of frailty (39-49) is currently proposed as the sum of physical, psychological and social deficits, with social frailty being, as yet, the least explored concept. Social frailty comprises alterations in three distinct social needs: affection, behavioral confirmation, and status (41).

The lower the levels of fulfillment of these three needs, the more socially vulnerable or frail the individual will be (42), which makes for a reduced level of life satisfaction (43). However, this link between frailty and life satisfaction is significant among younger older adults as they weaken with age (44). In the context of poverty and social vulnerability, frailty has also been linked to a higher incidence of geriatric syndromes (less physical activity and greater immobility, urinary incontinence, recurrent falls, and depressive and cognitive disorders) (45), and loneliness has been associated with adverse health outcomes such as depression, functional deterioration, and frailty, which are geriatric syndromes, and mortality (46).

This link could be due to the fact that inflammation associated with an increased activity of interleukin 6 (IL-6), C-reactive protein (CRP) and tumor necrosis factor alpha (TNF-a) is present in frail and in solitary individuals (47), while a poor social environment has been shown to significantly impact immunity (48) and poor social integration has been shown to alter neuroendocrine activity (49). On the other hand, it has been observed that positive emotions (feelings of happiness) attenuate the negative effects of perceived loneliness on physical activity and mortality (50).

A recent literature review in patients with head and neck tumors concluded that geriatric syndromes such as functional impairment, affective and cognitive disorders, and a deteriorated social environment were linked to adverse health outcomes (51). Another recent paper described how social isolation, inadequate environment, inadequate living conditions and meager resources are risk factors for loss of independence, and, as such, would require social criteria to be included in screening programs for frailty (52). Poverty is also associated with an increase in the prevalence of frailty; this could be explained by the effects, direct and indirect, of psychosocial factors such as perceived control and social isolation (53).

Similarly, when frailty and psychosocial factors are both present, their interaction tends to reduce the capacity to independently carry out activities of daily living (54), and pre-frail and frail older adults tend to have a smaller social network and higher levels of loneliness (55). A lower level of education also increases the risk of psychological and social frailty and reduced sleep duration, which is associated with the risk of physical, psychological and social frailty (56).

Comorbidity, allostatic load, low levels of physical activity, symptoms of depression, cognitive deterioration and poor social support can also predict the onset of frailty, with poor social support having a moderating effect on social integration (57). The various frailty trajectories are also related to social groups and social and behavioral factors in subjects aged 60-69 and 70-79. Thus, social and behavioral factors are associated with frailty.

The strongest of those associations are observed among the younger (58) and older. Female gender and marital status (being single) are also linked to the prevalence of frailty (59). The greater degree of social frailty is associated with a higher prevalence of disability (an increase of 66% among the socially frail as compared to the non-frail) (60), and this social vulnerability is associated with a higher mortality rate (61), although this associated negative effect weakens with age (62).

Social isolation, which is considered to be an objective and quantifiable reflection of the reduction in the size of the social network and the lack of social contact, is associated with an increased risk of developing cardiovascular disease (63), infectious diseases (64), cognitive impairment (65) and mortality (66). Once again, a link between social isolation and clinical disease has been described, the result of an increase in inflammatory activity (67) quantified by increases in CRP and fibrinogen (68, 69), and associated, in turn, with the onset of frailty.

There are three general paths by which social ties can have an impact on an individual’s health, according to behavioral, psychosocial and physiological characteristics (70). In fact, psychosocial mechanisms such as social support and the capacity for personal control influence physiological processes, thereby modulating the body’s immunity, metabolism and inflammatory capacity, all of which interferes with cardiovascular function.

The HPA axis is sensitive to the brain’s interpretation of threats and stressors and influences a wide range of physiological, behavioral, and health outcomes (71). Perceived social isolation is associated with increased HPA activity (72, 73), increased blood levels of catecholamines (74, 75), and with increases in cortisol and vascular resistance, mediated by a decrease in glucocorticoid receptor sensitivity (74).

Social isolation has been recognized as a significant risk factor for morbidity and mortality which may be mediated by neuroendocrine stress mechanisms, suggesting that chronic social isolation increases the activation of the HPA axis and that these effects depend on the interruption of a social bond: perceived social isolation activates an increased sensation of a threat and leads to an increase in symptoms of anxiety, hostility, fragmented sleep, fatigue, vascular resistance and genetic alterations, along with a decrease in impulse control, an increase in negativity and depressive symptomatology, as well as a greater, age-related deterioration in cognitive ability and the risk of dementia (34).

In fact, those persons with a low social risk profile are shown to live an average of 5.4 years longer than their high social risk profile counterparts. A review on lifestyle factors (76) demonstrates the influence social relationships have on survival, and it provides data from two meta-analyses to substantiate this. In these analyses, it was observed that people with adequate social networks or relationships were 50% more likely to survive than older adults with social problems or poor or insufficient social relationships.

Furthermore, it was observed that having a spouse or partner was also a significant predictor of survival, as evidenced by a 9-15% decrease in the risk of mortality (77). The authors of the review (76) point out that stronger social connections can alleviate stress and reduce the practice of poor lifestyle habits related to stress. However, any interpretation of the role many of these social factors play is hampered by the heterogeneity of life trajectories associated with genetic, social, environmental and biological factors, and with clinical conditions.

In addition, greater social vulnerability is a predictor of mortality and disability, although this relationship may be modulated by ethnographic and cultural factors, since this association was observed in continental European and Mediterranean countries, but not in Nordic countries (78). Reduced social support is also linked to lower survival rates in individuals with colorectal cancer. However, the same study does not indicate an objective relationship between social support and an increase in the incidence of site-specific neoplasms (79).

Social isolation predicts mortality regardless of gender; this would include social predictors such as not being married, and, among men, participating infrequently in religious activities or not belonging to clubs or social organizations; while among women, the predictors were infrequent social contact and reduced participation in religious activities (80). In fact, living alone is associated with a greater incidence of death due to unknown causes and murder (81).

A Japanese study of individuals living on remote islands described how living alone was significantly associated with a higher prevalence of frailty in men, but not in women (82). Similarly, patients from harsh social settings who are admitted to the hospital for a medical emergency present higher mortality rates, and are responsible for consuming more social resources and for a greater number of readmissions, although no differences in the length of hospital stay are identified (83).

One meta-analysis observed how real and perceived social isolation are associated with an increased risk of early mortality, with the following weighted average effects: OR = 1.29 for social isolation; OR = 1.26 for the feeling of loneliness; and OR = 1.32 for living alone. The authors conclude that as a predictor of mortality, social isolation demonstrates a capacity similar to other more established factors (26). One study associated living alone with a mortality of 1.66 (95% CI, 1.05-2.63), with a higher mortality rate observed for men than for women; furthermore, a higher mortality rate was observed for single, divorced or widowed folks than for those who are married (84).

Social isolation increases mortality in those who suffer chronic diseases involving proinflammatory mechanisms, as indicated by the observed high levels of fibrinogen and greater burden of inflammation in men (85). A link between mortality and isolation has also been observed in isolated and lonely people (86), in addition to the way in which social isolation and high poverty in the neighborhood were associated with an increased risk of cancer-related mortality, attenuated by socioeconomic status and with no observed synergistic effect (87).

There is a relationship between social isolation and loneliness; both are mortality predictors (88). However, after adjusting for confusing variables, only social isolation remained significant, and the relationship between social isolation and mortality was not affected by the presence of loneliness. A Finnish study (89) also observed the linear behavior of social isolation as a predictor of mortality and did not find a synergistic effect between social isolation and loneliness.

Loneliness is usually considered to be the psychological manifestation of social isolation, a reflection of the dissatisfaction the individual experiences regarding the frequency and closeness of his or her social contacts or the discrepancy between the relationships they have and the relationships they would like to have (90). Loneliness is linked to greater access to negative social information (91), with solitary people being more sensitive to pained facial expressions (92).

A study involving functional magnetic resonance also indicated that loneliness is associated with greater activation of the visual cortex in response to negative social images (93). Loneliness was also associated with higher levels of cortisol (67, 74, 74) and impaired immune activity (95, 96) linked to the genesis of frailty. In this way, there is an increase in vascular resistance (97), sleep that is more fragmented (98), and an increased risk of cardiovascular disease and mortality (99, 100). In fact, the score on the frailty index was associated with loneliness, functionality and gender, with loneliness being the factor that contributed most to the frailty index score (101).

The feeling of loneliness, in addition to clinical frailty, increased the length of hospital stays and the rates of hospital readmission for patients who lived alone (102). However, the link between loneliness and increased mortality is not clear: one cohort study conducted in Israel found no relationship between loneliness, functional and affective deterioration, and increased comorbidity or mortality (103), although another cohort study did find associations between loneliness and a significant increase in the risk of mortality, especially among women (104).

The PAQUID study (105) determined that living alone and the frequent feeling of loneliness were both risk factors for mortality: Loneliness has been linked to premature mortality (106), with an increased risk of mortality mediated by the presence of a diagnosis of severe depression in men (107) and with genetic changes linked to the perception of loneliness that would decrease survival in patients with cancer (108).

A study of institutionalized older adults found that independent of the diagnosis of cancer, emotional loneliness, age, education and comorbidity had an impact on mortality rates among elderly residents with no cognitive impairment (109). A subanalysis of the AMSTEL study observed how the feeling of loneliness, but not social isolation itself, was associated with a greater risk of developing dementia (110), though it is possible that the perception of loneliness may be indicative of a prodromal stage of dementia.

Likewise, socioeconomic status has been associated with mortality in patients with chronic kidney disease for whom multiple deprivation and serum phosphate levels were predictors of mortality (111), and a low socioeconomic level was associated with living alone, being single, with a pre-existing comorbidity, substance abuse, with the highest rate of bacteremia due to Staphylococcus aureus and nosocomial infections, with a higher rate of hospital admissions, and with higher mortality rates (112).

reference link : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6179015/


Original Research: Open access.
Loneliness and social isolation increase cancer incidence in a cohort of Finnish middle-aged men. A longitudinal study” by Kraav, S., Lehto, S.M., Kauhanen, J., Hantunen, S., Tolmunen, T. Psychiatry Research

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