The Lancet published a 12 year population-based cohort study on the association between loneliness and depressive symptoms among adults aged 50 years and older. This is a short version of the article. November 2020.
Siu Long Lee, MSc Eiluned Pearce, PhD Olesya Ajnakina, PhD Prof Sonia Johnson, MD Prof Glyn Lewis, PhD Farhana Mann, MSc Alexandra Pitman, PhD Francesca Solmi, PhD Andrew Sommerlad, PhD Prof Andrew Steptoe, DSc Urszula Tymoszuk, PhD Gemma Lewis, PhD
Loneliness is experienced by a third of older adults in the UK and is a modifiable potential risk factor for depressive symptoms. It is unclear how the association between loneliness and depressive symptoms persists over time, and whether it is independent of related social constructs and genetic confounders.
We aimed to investigate the association between loneliness and depressive symptoms, assessed on multiple occasions during 12 years of follow-up, in a large, nationally representative cohort of adults aged 50 years and older in England.
Depression among older adults is common (with an estimated prevalence of 4–9% worldwide),1 potentially underdiagnosed and undertreated, and associated with substantial morbidity and mortality.1 Data from the past 15 years suggest that the prevalence of depressive illness among older adults is increasing.2 Better identification of modifiable risk factors for depression would inform public health and clinical approaches to prevention.
Loneliness is a painful emotional state caused by a discrepancy between a person’s desired meaningful social relationships, and what relationships they perceive they have.3, 4 Loneliness is related to, but distinct from, other aspects of social relationships such as objective social isolation and perceived social support.3, 4
Around a third of people aged 50 years and older in the UK report loneliness,5which might partly be due to factors such as retirement, physical and cognitive decline, bereavement, reduced social networks, and loss of social roles. There is substantial overlap between the constructs of loneliness and depression, although there is also evidence that they are distinct.6
Theoretical models suggest that loneliness has social, cognitive, and biological consequences that could increase the risk of subsequent depression.7 Potential mechanisms for this association include negative perceptions of social interactions, negative cognitive schemas (eg, low self-belief), expectations of social threat, increased stress, reduced self-esteem, and biological effects on the stress response and inflammation.7There is also evidence that loneliness is associated with anticipated rejection and reduced reward responsiveness to positive stimuli.7
Many studies have examined the relationship between loneliness and depression in older adults, but these studies have had limitations.8, 9 There have been several cross-sectional studies,10, 11, 12, 13, 14, 15, 16 but it is impossible to rule out reverse causation in studies with a cross-sectional design. Longitudinal studies are essential to establishing whether loneliness precedes depressive symptoms, which is a necessary condition for identifying loneliness as a potentially causal, and hence targetable, risk factor for depression.
Existing longitudinal studies also have had limitations. Several small longitudinal studies (ie, sample sizes of less than 400 participants) have found evidence that higher levels of loneliness are associated with future depressive symptoms among older adults.17, 18, 19, 20, 21, 22 Some of these studies used clinical17, 20 or convenience21samples, which introduces selection bias and reduces generalisability. Small studies might also not be statistically powered to produce valid and precise results.23Several large population-based cohort studies have reported positive associations between loneliness and subsequent depression,24, 25, 26, 27, 28 although one study found no evidence of a relationship.29
Most of these studies used single-item measures of loneliness24, 25, 26, 27, 28, 29 which, compared with multi-item loneliness scales, are more susceptible to social desirability biases. Two large population-based cohort studies have found positive associations between loneliness, assessed using multi-item scales, and a single follow-up measure of depressive symptoms 2 years later.26, 27Studies with longer follow-up periods or repeated assessments of the depression outcome are scarce,19, 27, 28, 29 but would provide evidence on how the association between loneliness and depression changes over time. This evidence would strengthen causal inferences and inform the timing of interventions to prevent depression.
To our knowledge, the longest follow-up in any previous study has been 7 years, but this study found no evidence of an association between loneliness and depressive symptoms.29 The extent to which the association persists over time is therefore unclear. There have been three studies with repeated assessments of loneliness and depression, but these studies have used cross-lagged panel analyses.19, 27, 28 Although these models are valuable for comparing bidirectional relationships, they often do not have follow-up periods of longer than 2–3 years (because each outcome follows the exposure immediately before it).
Loneliness is associated with objective social isolation and perceived social support, and it is possible that associations between loneliness and depressive symptoms are confounded by these related social experiences. Only one large cohort study adjusted for a broad range of social constructs and confounders related to loneliness. An independent association between loneliness and depressive symptoms was reported, although this study used a single-item loneliness measure and a single follow-up.26
If there is an independent influence of loneliness, irrespective of other social experiences, it would suggest that interventions need to target loneliness, in addition to targeting social isolation and providing social support.Loneliness and depression are moderately heritable.30, 31
Molecular investigations reveal substantial overlap between genes that influence loneliness and genes that influence depression.32 This overlap could introduce genetic confounding of associations between loneliness and depression which, as far as we know, has never been investigated. One way to account for possible genetic confounding is to adjust for polygenic risk scores. Gene variants are derived from genome-wide association studies and combined into a single polygenic risk score, which captures part of an individual’s genetic susceptibility to the outcome (eg, depression or loneliness).33
Depressive symptoms in the previous week were assessed at every timepoint using the eight-item version of the Centre for Epidemiologic Studies Depression Scale (CES-D). Scores ranged from 0 to 8, and higher scores indicated greater severity of depressive symptoms. The eight-item CES-D is widely used in older adults and has been validated against the 20-item version, showing good validity and reliability.35
The CES-D contains an item that asks whether respondents have felt lonely. Consistent with other studies,19, 36 we removed this item to avoid overlap with the loneliness scale, which might inflate associations. The CES-D showed good internal consistency before (α=0·78) and after (α=0·76) removing the loneliness item, at each wave.
Our primary outcome was CES-D scores (using seven items, with loneliness removed) after the baseline assessment of loneliness (waves three to eight), as a repeated measure. Our secondary outcome was depression measured using a binary version of the CES-D. The recommended score cutoff approximating clinical diagnosis of depression on the eight-item CES-D (including the loneliness item) is 3 or higher.37
For our revised seven-item scale (with the loneliness item removed), we used a score cutoff of 2 or higher, which resulted in the same prevalence of depression as the cutoff of 3 or higher on the eight-item version of the CES-D.Loneliness was measured at waves two to eight. At each of these waves the three-item short 1980 version of the University of California, Los Angeles Loneliness Scale (R-UCLA) was used.38
We used the baseline scores from wave two as the main exposure for loneliness. The scale asks “how often do you feel you lack companionship?”, “how often do you feel left out?”, and “how often do you feel isolated from others?”. Response options for each item are “hardly ever or never” (equating to a score of 1), “some of the time” (a score of 2), or “often” (a score of 3). Total scores for the scale range from 3 to 9, and higher scores indicate greater loneliness. The scale has been used extensively with older adults, with good internal reliability (α=0·78).36
We selected confounders on the basis of existing studies and theoretical assumptions. We assumed that these variables were potential alternative explanations for the association between exposure and outcome.
It is possible that associations between loneliness and depressive symptoms are confounded by related social experiences.19 We therefore adjusted for measures of social network size, frequency of social contact, participation in social groups, and perceived social support. These measures were from wave two and are described in the appendix (p 3)). Consistent with other studies,36 we assumed that objective social isolation (having little social contact with others) would be captured by social network size, frequency of social contact, and participation in social groups.
We also adjusted for: polygenic risk scores for loneliness and depressive symptoms, age, sex, ethnicity, marital status, level of education, employment status, wealth, long-term physical illness, mobility impairment, pain, body-mass index, waist circumference, cognitive function, and baseline depressive symptoms.
Wealth is generally used as the measure of socioeconomic resources in ageing studies because of the difficulty in income measurement in retired people.36 Even among those who work, incomes are often reduced at older ages because part-time work is more common. All confounders were measured at wave two and are described in the appendix (pp 4–6).
Of 9171 eligible participants, our complete case sample included 4211 participants (46%; figure) aged 52–101 years (mean 65·1, SD 8·9); 2310 (55%) were female, 2785 (66%) were unemployed or retired, and 4211 (100%) were white (table 1, appendix pp 8–9). The mean loneliness score at baseline (wave two) was 4·12 (SD 1·50). Mean depressive symptom severity scores increased slightly over time and were higher in the group with high loneliness scores (score of ≥6; table 2).
At baseline, 17% of the sample had a depression severity score of 2 or higher on the CES-D and this was similar during follow-up. At baseline, there was a moderate positive correlation between loneliness and depression (Pearson’s correlation coefficient 0·44 when including the CES-D loneliness item and 0·49 when not including the loneliness item).
Compared with those with low loneliness scores (score of <6), participants with high loneliness scores (≥6) were on average older and a higher proportion were female, unmarried, unemployed, and had lower level of education and wealth (table 1).
The group with high loneliness scores also had more physical illnesses, mobility impairment, and pain, as well as more severe depressive symptoms, lower levels of social support, smaller social network sizes, and less frequent social contact.
However, participation in social groups was more common in the group with high loneliness scores (table 1). Participants with missing data were older than those in the complete case sample and more likely to be unmarried, from an ethnic minority, and of lower socioeconomic status (appendix pp 8–9). Participants with missing data also had higher scores on loneliness, depressive symptoms, and social isolation, and were more likely to have experienced mobility impairment or be often troubled with pain (appendix pp 8–9).