RESEARCH ARTICLE

Physical multimorbidity and loneliness: A

population-based study
Andrew Stickley1*, Ai Koyanagi2,3
1 The Stockholm Center for Health and Social Change (SCOHOST), Södertörn University, Huddinge,
Sweden, 2 Parc Sanitari Sant Joan de Déu, Universitat de Barcelona, Fundació Sant Joan de Déu, Sant Boi
de Llobregat, Barcelona, Spain, 3 Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de
Salud Mental, CIBERSAM, Madrid, Spain

* amstick66@gmail.com

a1111111111
a1111111111
a1111111111 Abstract
a1111111111
a1111111111 Multimorbidity has been linked to a variety of negative outcomes although as yet, there has
been little research on its association with loneliness. This study examined the association
between physical multimorbidity ( 2 physical diseases) and loneliness in the general popu-
lation and its potential mediators. Data came from the Adult Psychiatric Morbidity Survey
OPEN ACCESS 2007 (N = 7403, aged 16 years). Information was obtained on 20 doctor diagnosed physi-
Citation: Stickley A, Koyanagi A (2018) Physical
cal conditions that were present in the previous year. An item from the Social Functioning
multimorbidity and loneliness: A population-based Questionnaire (SFQ) was used to obtain information on loneliness. Multivariable logistic
study. PLoS ONE 13(1): e0191651. https://doi.org/ regression analysis was used to examine associations. An increasing number of physical
10.1371/journal.pone.0191651
diseases was associated with higher odds for loneliness. Compared to no physical dis-
Editor: Antony Bayer, Cardiff University, UNITED eases, the odds ratio (OR) (95% confidence interval: CI) for loneliness increased from 1.34
KINGDOM
(1.13–1.59) to 2.82 (2.11–3.78) between one and 5 physical diseases. This association
Received: July 29, 2017 was particularly strong in the youngest age group (i.e. 16–44 years). The loneliness-physical
Accepted: January 9, 2018 multimorbidity association was significantly mediated by stressful life events (% mediated
Published: January 24, 2018
11.1%-30.5%), anxiety (30.2%), and depression (15.4%). Physical multimorbidity is associ-
ated with increased odds for loneliness. Prospective research is now needed to further eluci-
Copyright: © 2018 Stickley, Koyanagi. This is an
open access article distributed under the terms of
date this association and the factors that underlie it.
the Creative Commons Attribution License, which
permits unrestricted use, distribution, and
reproduction in any medium, provided the original
author and source are credited.

Data Availability Statement: The data used in this

study are third party data (i.e., they are not owned Introduction
and were not collected by the authors) that have
been made publicly available by the National Center
Multimorbidity (the presence of 2 or more chronic/acute diseases) is common in the general
for Social Research via the UK data archive. The population [1]. A recent study that used World Health Survey data from 27 low- and middle-
authors did not have any special access privileges income countries (LMICs) and 1 high-income country (HIC) showed that the prevalence of
and other authors can access these data in the multimorbidity ranged from 1.7% (Myanmar) to 15.2% (Nepal) and averaged 7.8% across all
same manner as the authors in this study did, i.e., LMICs countries [2]. Although research has indicated that the prevalence of multimorbidity
registration is required and standard conditions of
increases with age, it is observed in all adult age groups [2,3]. This is alarming as the co-occur-
use apply. Details of how to access the Adult
Psychiatric Morbidity Survey 2007 dataset are
rence of chronic disease has been associated with a variety of negative outcomes including
available at: https://discover.ukdataservice.ac.uk/ worse quality of life [4], poorer physical function [5], greater health care use [6], as well as an
catalogue/?sn=6379. increased risk for premature mortality [7].

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 Physical multimorbidity and loneliness

Funding: Ai Koyanagi’s work was supported by the The current study will examine physical multimorbidity—the co-occurrence of 2 or more
Miguel Servet contract financed by the CP13/ physical diseases. Although there has been increased attention on this phenomenon recently
00150 and PI15/00862 projects, integrated into the
[8–11], there are still many gaps in our knowledge. For example, relatively little is known
National R + D + I and funded by the ISCIII -
General Branch Evaluation and Promotion of Health about the association between physical multimorbidity and loneliness, that is, “the unpleasant
Research - and the European Regional experience that occurs when a person’s network of social relations is deficient in some impor-
Development Fund (ERDF-FEDER). These tant way, either quantitatively or qualitatively” [12]. This may be an important omission. Lone-
organizations had no role in the study design, liness is not only common in the general population with studies showing that on average,
collection, analysis and interpretation; in the writing
approximately 5–15% of people report often feeling lonely [13–16], but there is some evidence
of the manuscript; and in the decision to submit
the paper for publication.
that loneliness might be a significant factor for health in its own right. Specifically, feeling
lonely has been linked to an increased risk for a variety of adverse health outcomes including
Competing interests: The authors have declared
premature mortality [17–19].
that no competing interests exist.
Importantly, previous research has indicated that there might be an association between
physical disease and loneliness. In particular, an earlier study found that there was an increased
risk for loneliness in individuals with chronic diseases [20]. Other studies have also shown an
association between feeling lonely and heart disease, hypertension, stroke [21–23] and Alzhei-
mer disease [24]. However, this research has also indicated that not all physical diseases are
linked to loneliness and that the association between loneliness and specific diseases may vary
between different population subgroups [21].
Despite these studies linking physical disease and loneliness, as yet, there has been compar-
atively little research on the association between physical multimorbidity and loneliness.
Moreover, to the best of our knowledge, the few studies undertaken to date on the association
between the number of illnesses/multimorbidity and loneliness or vice versa have been con-
fined to middle-aged and older adults (age  45) and produced mixed results [25–29]. Specifi-
cally, while studies among adults aged 52–92 in Denmark, 65 and above in the United States
and 75 and above in Israel respectively linked the number of chronic illnesses and greater
comorbidity to loneliness [25,27,28], a study among veterans aged 60 and above in the United
States found that a bivariate association between the number of medical conditions and loneli-
ness became non-significant in a stepwise linear regression analysis [29]. In addition, research
undertaken among men and women aged 45 and above in Canada and Australia found that
multimorbidity was significantly linked to loneliness in all age-sex groups except among Aus-
tralian women aged 75 and above [26].
Given the absence of research on the association between (physical) multimorbidity and
loneliness among adults of all ages and the mixed findings from research that has focused on
the multimorbidity-loneliness association in middle-aged and older adults, the current study
had two aims: (1) to examine the association between physical multimorbidity and loneliness
in a general population sample; and (2) to determine if any factors might be important for this
association.

Materials and methods

Study population
This study used data from the Adult Psychiatric Morbidity Survey (APMS) 2007 (N = 7403).
Details of the survey have been published elsewhere previously [30]. In brief, the survey was
conducted in England between October 2006 and December 2007 by the National Center for
Social Research and Leicester University. To obtain a nationally representative sample of the
adult population aged 16 years old residing in private households, multistage stratified prob-
ability sampling was used. The small user Postcode Address File (PAF) served as the sampling
frame with postcode sectors serving as the primary sampling units (PSUs). Sectors were strati-
fied by both region and socioeconomic status. One person was randomly selected from each

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 Physical multimorbidity and loneliness

randomly selected household. The survey response rate was 57% (respondents from 7461/
13171 eligible households agreed to participate). To correct for survey non-response, sampling
weights were generated to ensure that the sample was representative of its intended target pop-
ulation. Details of the weighting procedure are provided in the survey report [30]. The Royal
Free Hospital and Medical School Research Ethics Committee provided ethical approval for
the study. The survey methodology was carried out in accordance with the relevant guidelines
and regulations with all participants providing written informed consent.

Data availability
The data used in this study are third party data (i.e., they are not owned and were not collected
by the authors) that have been made publicly available by the National Center for Social
Research via the UK data archive. The authors did not have any special access privileges and
other authors can access these data in the same manner as the authors in this study did i.e. reg-
istration is required and standard conditions of use apply. Details of how to access the Adult
Psychiatric Morbidity Survey 2007 dataset are available at: https://discover.ukdataservice.ac.
uk/catalogue/?sn=6379

Main measures
Physical illnesses. A question which enquired about the presence of 20 physical health
conditions was used to assess physical illnesses (cancer, diabetes, epilepsy, migraine, cataracts/
eyesight problems, ear/hearing problems, stroke, heart attack/angina, high blood pressure,
bronchitis/emphysema, asthma, allergies, stomach ulcer or other digestive problems, liver
problems, bowel/colon problems, bladder problems/incontinence, arthritis, bone/back/joint/
muscle problems, infectious disease, and skin problems). To be counted, conditions had to
have been diagnosed by a doctor or other health professional and have been present in the pre-
vious 12 months. The number of physical diseases was summed and categorized as 0, 1, 2, 3, 4,
and 5. Multimorbidity was defined as two or more physical diseases [31].
Loneliness. This was measured with one item from the Social Functioning Questionnaire
(SFQ) [32]. Respondents were asked to assess to what extent they had felt ‘lonely and isolated
from other people’ in the previous two weeks. The answer options were ‘very much’, ‘some-
times’, ‘not often’, and ‘not at all’. In the current study, response options were dichotomized
with those who answered ‘sometimes’ and ‘very much’ being categorized as lonely [33].

Covariates
Smoking. The question, ‘Have you ever smoked a cigarette?’ with ‘yes’ or ‘no’ answer
options was used to assess smoking status.
Alcohol dependence. This was assessed with two instruments. The Alcohol Use Disorders
Identification Test (AUDIT) was firstly used to assess alcohol consumption [34]. When a
respondent’s AUDIT score was  10 they were also assessed for alcohol dependence using the
Severity of Alcohol Dependence Questionnaire (SADQ-C) [35]. Those who scored  4/60 on
this measure were categorized as having past 6-month alcohol dependence.
Drug use. Information was obtained on the past year use of the following drugs: cannabis,
amphetamines, cocaine, crack, ecstasy, heroin, acid or LSD, magic mushrooms, methadone or
physeptone, tranquilizers, amyl nitrate, anabolic steroids, and glues. Respondents taking any
of these drugs were categorized as past 12-month drug users.
Disordered eating. Possible eating disorder was assessed with five items from the SCOFF
eating disorder screening tool [36]. Respondents were asked whether, in the past year, they (1)
had lost more than one stone (6.35kg) in 3 months; (2) had made him/herself be sick because

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 Physical multimorbidity and loneliness

he/she felt uncomfortably full; (3) had worried that he/she had lost control over how much he/
she eats; (4) believed [himself/herself] to be fat when others said that he/she was too thin; and
(5) thought that food dominated his/her life. Using yes/no response options, a positive screen
was categorized as two or more affirmative answers [36].
Obesity. Self-reported weight and height data were used to determine body mass index
(BMI), calculated as weight in kilograms divided by height in meters squared. As a preliminary
examination of the data revealed that only extreme levels of obesity were associated with lone-
liness, we used 35 kg/m2 (obesity class I) as the cut-off.
Stressful life events. Seventeen questions on the lifetime occurrence of experiences such
as the death of a family member, financial crises, sexual abuse etc., were used to assess stressful
life events (S1 Table). Two different stressful life events measures were constructed depending
on whether the event last occurred when the respondent was <16 or 16 years of age. For the
latter measure, a summed total number of stressful life events was based on all 17 questions,
while 8 age-appropriate potentially stressful life events were assessed before age 16 (all of
which had a prevalence of at least 2%) (S1 Table).
Depressive episode and anxiety disorders. The Clinical Interview Schedule Revised
(CIS-R), was used to identify non-psychotic symptoms in the prior week to generate ICD-10
diagnoses of depressive episode and anxiety disorders (generalized anxiety disorder, panic dis-
order, phobia, obsessive-compulsive disorder) [37].
Social support. This was assessed with a 7-item measure. Using answer options ‘not true’
(score = 0), ‘partly true’ (score = 1) and ‘certainly true’ (score = 2), participants responded to
statements which inquired if, family and friends did things to make them happy, made them
feel loved, could be relied on no matter what, would see that they were taken care of no matter
what, accepted them just the way they are, made them feel an important part of their lives, and
gave them support and encouragement. Responses were added to create a scale score that
could range from 0 to 14. The internal consistency of the scale was good: α = 0.89.
Socio-demographic variables. Information was also obtained on age, sex, equivalized
income tertiles (high £29826, middle £14,057 to < £29826, low <£14,057), education [quali-
fication (degree, non-degree, A-level, GCSE, other): yes or no)], and ethnicity (white British or
other).

Statistical analysis
Differences in sample characteristics by the presence of loneliness were tested with Chi-square
tests and Student’s t-tests for categorical and continuous variables, respectively. To examine
the association between physical multimorbidity and loneliness, a multivariable logistic regres-
sion analysis was performed with loneliness as the dependent variable and the number of phys-
ical diseases as the independent variable that adjusted for the socio-demographic variables
(age, sex, income, education, and ethnicity). An age-stratified analysis was also conducted to
assess whether the association differed between different age groups.
To determine if any factors mediated the association between loneliness and physical multi-
morbidity (i.e., 2 physical diseases) (outcome), a meditation analysis was performed using
the khb (Karlson Holm Breen) command in Stata [38]. This method can be used with logistic
regression analysis to decompose the total effect of a variable into its direct and indirect effects
(i.e., mediational effect). This allows the percentage of the main association explained by the
mediator to be calculated (mediated percentage). Potential mediators (smoking, alcohol
dependence, drug use, disordered eating, obesity, stressful life events, social support, depres-
sion, anxiety) were selected using past literature as a guide. Each potential mediator was
included in the model individually. The mediation analysis controlled for the five socio-

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 Physical multimorbidity and loneliness

demographic variables. In order to assess whether the mediators differ by age group, we also
conducted age-stratified analyses.
As nearly 20% of the participants had missing income information and in order to avoid
the exclusion of a large number of respondents, a missing category for this variable was
included in all regression analyses. Age-stratified analyses were not adjusted for age. All vari-
ables were included in the models as categorical variables, excepting the stressful life events
and social support variables (continuous). The sample weighting and the complex study design
were taken into account in order to generate nationally representative estimates. Odds ratios
(OR) and 95% confidence intervals (95%CI) are reported. The level of statistical significance
was set at P<0.05. All analyses were performed with Stata version 14.1 (Stata Corp LP, College
Station, Texas).

Results
There were significant differences between lonely and non-lonely people for all of the sample
characteristics except for ethnicity and smoking status (Table 1). Lonely people were more
likely to have two or more physical diseases. A graded association between the presence of
physical disease and loneliness is illustrated in Fig 1 with the prevalence of loneliness rising
from 16.5% in those with no physical diseases to 30.7% among those with 5 or more diseases.
Besides a higher number of physical diseases, lonely people also had a higher prevalence of
adverse outcomes such as alcohol dependence, drug use, stressful events across the life course,
poorer mental health (anxiety and depression) and lower social support.
In a multivariable logistic regression analysis that controlled for socio-demographic factors,
there was a statistically significant monotonic association between the number of physical dis-
eases (independent variable) and loneliness (dependent variable) with the OR for loneliness
rising from 1.34 (95% CI: 1.13–1.59) for those with one disease to almost 3 (OR: 2.82, 95% CI:
2.11–3.78) for those with 5 or more diseases, compared to those with no physical diseases.
When the analysis was stratified by age, the associations were stronger across all levels of dis-
ease in the youngest age group (16–44 years) (Table 2).
The mediation analysis showed that stressful life events both before and after 16 years of
age mediated 11.1% and 30.5% of the association between loneliness and multimorbidity,
respectively, while depression (15.4% mediated), anxiety (30.2%) and disordered eating
(10.1%) were also important mediators. In contrast, there were no significant mediational
effects for smoking, alcohol dependence, drug use, obesity or social support (Table 3). When
an age-stratified mediation analysis was performed, the same variables were important for
adults aged 16–44 and 45–64. Specifically, depression, anxiety, stressful life events before and
after age 16 and disordered eating were all significant mediators in the association between
multimorbidity and loneliness although stressful life events in adulthood was the strongest
mediator for adults aged 16–44 whereas for adults aged 45–64, anxiety was the strongest medi-
ator. For adults aged 65 and above the only variable which was a significant mediator was
stressful life events in adulthood which mediated 11.8% of the association (S2 Table).

Discussion
This study examined the association between multiple co-occurring physical diseases and
loneliness in a nationally representative sample of the English population. The results showed
that the number of co-occurring physical diseases was associated with loneliness in a dose-
response fashion after adjustment for socio-demographic factors, particularly in the youngest
age group (aged 16–44 years). In addition, stressful life events across the life course and poor

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 Physical multimorbidity and loneliness

Table 1. Sample characteristics (overall and by loneliness).

Characteristic Category Overall Loneliness P-valuea
No Yes
Number of physical diseases 0 2,373 36.5 1,961 38.3 412 29.6 <0.001
1 2,020 28.3 1,593 28.6 427 27.5
2 1,335 16.7 1,017 16.3 318 18.5
3 804 9.4 587 8.9 217 11.3
4 402 4.6 276 4.1 126 6.4
5 423 4.5 279 3.9 144 6.7
Age (y) 16–44 2,871 48.1 2,183 47.0 688 52.4 <0.001
45–64 2,406 32.3 1,864 32.6 542 31.2
65 1,954 19.6 1,564 20.4 390 16.5
Sex Male 3,176 48.6 2,544 50.1 632 42.8 <0.001
Female 4,184 51.4 3,172 49.9 1,012 57.2
Income High 1,972 35.9 1,623 37.4 349 29.5 <0.001
Middle 1,932 32.6 1,512 32.9 420 31.5
Low 1,957 31.5 1,426 29.7 531 39.0
Qualification No 2,103 23.9 1,570 23.3 533 26.1 0.041
Yes 5,225 76.1 4,123 76.7 1,102 73.9
Ethnicity British White 6,478 85.2 5,053 85.5 1,425 84.1 0.285
Other 847 14.8 639 14.5 208 15.9
Smoking No 2,481 34.7 1,971 35.3 510 32.2 0.339
Yes 4,879 65.3 3,745 64.7 1,134 67.8
Alcohol dependence No 6,995 94.1 5,493 95.4 1,502 89.2 <0.001
Yes 365 5.9 223 4.6 142 10.8
Drug use No 6,813 90.7 5,369 92.3 1,444 84.7 <0.001
Yes 534 9.3 340 7.7 194 15.3
Disordered eating No 6,897 93.6 5,500 96.2 1,397 83.2 <0.001
Yes 450 6.4 206 3.8 244 16.8
Obesity class I (BMI35 kg/m2) No 6,617 94.6 5,163 95.0 1,454 93.0 0.009
Yes 388 5.4 280 5.0 108 7.0
Stressful life events (16 years)b Mean (SD) 2.6 (2.0) 2.5 (1.9) 3.3 (2.5) <0.001
Stressful life events (<16 years)c Mean (SD) 0.5 (1.0) 0.4 (0.9) 0.8 (1.2) <0.001
Social supportd Mean (SD) 13.2 (1.9) 13.4 (1.6) 12.4 (2.8) <0.001
Depression No 7,109 97.0 5,651 99.0 1,458 89.3 <0.001
Yes 251 3.0 65 1.0 186 10.7
Anxiety No 6,828 93.3 5,537 97.0 1,291 78.7 <0.001
Yes 532 6.7 179 3.0 353 21.3

Note: Boldface type indicates statistical significance (p<0.05).

Abbreviation: SD standard deviation; Data are unweighted N and weighted percentage or mean (SD).
a
The differences in sample characteristics was tested by Chi-square tests and Student’s t-tests for categorical and continuous variables respectively.
b
Based on 17 stressful life events occurring at the age of 16 or after.
c
Based on 8 stressful life events occurring before the age of 16.
d
Seven items were used to identify the level of social support with each item having scores of 0, 1, or 2. Scores of the 7 items were added to create a scale ranging from
0–14 with higher scores corresponding to higher levels of social support.

https://doi.org/10.1371/journal.pone.0191651.t001

mental health (anxiety and depression) were important mediators in the association between
multimorbidity and loneliness.
Although prior research has produced mixed results on the association between the number
of diseases/multimorbidity and loneliness [25–29], the results of the current study accord with

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 Physical multimorbidity and loneliness

Fig 1. Prevalence of loneliness by the number of physical diseases. Bars denote 95% confidence intervals. Estimates are based on
weighted sample.
https://doi.org/10.1371/journal.pone.0191651.g001

previous studies which showed an association [25–28], and which also found that the strength
of the association varied between different populations/population subgroups [26]. The exact
way in which physical disease and loneliness are linked is uncertain although the results from
the mediation analysis point to several possible pathways. In particular, mental illness was an
important mediator in the association. This accords with research which has linked physical
multimorbidity and depression [10], possibly due to the feelings of inadequacy, dependency
and dejection it can give rise to [39], as well as with studies which have shown that worse men-
tal health is associated with loneliness [40]. In terms of the specific association, a recent study
found that depression was linked to lower participation in social leisure activities in older
adults with multimorbidity [41] which might be important for feelings of loneliness.
Stressful life events across the life course (both before and after age 16) were also an impor-
tant factor in the association between multimorbidity and loneliness. Research has shown that
stressful events in early life are linked to an increased risk for both later multimorbidity and
loneliness [42,43] possibly as a result of physiological changes they may cause that might
increase the risk for future disease [44] as well as through problems with bonding and trust
[43]. Given this, it is possible that such events might be a common third factor underlying the
occurrence of both multimorbidity and loneliness in adulthood. Alternatively, stressful life
events might also mediate the association with loneliness. For example, stressors such as
divorce, separation and widowhood that might be important for loneliness have been associ-
ated with multimorbidity in middle-aged adults [45]. Another adult stressor which might be a
direct consequence of co-occurring physical diseases—an inability to work—might also play a
role here, as multimorbidity has been associated with unemployment [46] which in turn,
might be important for loneliness [12,47].

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 Physical multimorbidity and loneliness

Table 2. Association between number of physical diseases and loneliness estimated by multivariable logistic regression analysis.
Overall Age (16–44 years) Age (45–64 years) Age (65 years)
Characteristics OR 95%CI OR 95%CI OR 95%CI OR 95%CI
Number of physical diseases
0 1.00 1.00 1.00 1.00
1 1.34 [1.13,1.59] 1.41 [1.14,1.75] 0.91 [0.61,1.37] 0.93 [0.61,1.43]
2 1.66 [1.37,2.02] 1.84 [1.39,2.45] 1.24 [0.82,1.89] 1.28 [0.83,1.97]
3 1.92 [1.52,2.43] 2.24 [1.49,3.37] 1.47 [0.96,2.23] 1.53 [0.99,2.35]
4 2.57 [1.92,3.43] 2.97 [1.68,5.25] 1.77 [1.09,2.89] 1.78 [1.08,2.93]
   
5 2.82 [2.11,3.78] 3.09 [1.53,6.24] 1.90 [1.23,2.93] 1.94 [1.25,3.01]
Age (years)
16–44 1.00
45–64 0.70 [0.61,0.82]
65 0.44 [0.37,0.53]
Sex
Male 1.00 1.00 1.00 1.00
Female 1.21 [1.07,1.37] 1.16 [0.96,1.41] 1.73 [1.34,2.24] 1.75 [1.34,2.28]
Income
High 1.00 1.00 1.00 1.00
Middle 1.22 [1.03,1.44] 1.09 [0.83,1.43] 1.49 [0.89,2.51] 1.51 [0.88,2.61]
Low 1.62 [1.37,1.91] 1.65 [1.28,2.12] 1.29 [0.77,2.15] 1.28 [0.74,2.21]
Qualification
No 1.00 1.00 1.00 1.00
Yes 0.84 [0.71,0.99] 0.73 [0.52,1.04] 0.68 [0.54,0.86] 0.67 [0.53,0.85]
Ethnicity
British White 1.00 1.00 1.00 1.00
Other 1.06 [0.86,1.31] 1.07 [0.83,1.37] 1.46 [0.80,2.67] 1.44 [0.74,2.78]

Note: Boldface type indicates statistical significance ( p<0.05,  p<0.01,  p<0.001)
Abbreviation: OR odds ratio; CI confidence interval
Models are adjusted for all variables in the respective columns.

https://doi.org/10.1371/journal.pone.0191651.t002

As this study was cross-sectional it was not possible for us to establish causality or deter-
mine the direction of the observed associations. It is possible therefore that loneliness might
also have led to multimorbidity. For instance, it has been suggested that the hypervigilance for
social threats in the surrounding environment, distorted cognitions and a negative disposition
(e.g. feelings of stress, anxiety, hostility) that are all associated with loneliness may result in
behavioral and physiological changes that can impact negatively on health [48]. Indeed, there
is a growing body of evidence that loneliness is linked to biological changes that might be
adverse for health such as higher systolic blood pressure [49], differences in diastolic blood
pressure reactivity [50] and cardiovascular functioning [51], as well as an increased risk for
metabolic syndrome [52] that might underlie co-occurring physical diseases. Our finding that
stressful life events link multimorbidity and loneliness also provides some support for the idea
that loneliness might be a precursor of physical disease and multimorbidity as previous
research has indicated that (perceived) stress may mediate the association between loneliness
and physical ill health [53,54].
Stratifying the analysis by age revealed that the association between physical multimorbidity
and loneliness was strongest in the youngest age group. Given that multimorbidity has been
associated with increasing age [55] and that it has been hypothesized that the effects of

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 Physical multimorbidity and loneliness

Table 3. Lifestyle and other potential mediators in the association between loneliness and multimorbidity.
Mediator Effect OR 95%CI P-value % Mediated
Smoking Total 1.67 [1.46, 1.91] <0.001 NA
Direct 1.66 [1.46, 1.90] <0.001
Indirect 1.01 [1.00, 1.01] 0.085
Alcohol dependence Total 1.67 [1.46, 1.91] <0.001 NA
Direct 1.65 [1.44, 1.88] <0.001
Indirect 1.01 [1.00, 1.03] 0.078
Drug use Total 1.67 [1.46, 1.91] <0.001 NA
Direct 1.65 [1.44, 1.88] <0.001
Indirect 1.01 [1.00, 1.03] 0.137
Disordered eating Total 1.67 [1.46, 1.91] <0.001 10.1
Direct 1.58 [1.38, 1.81] <0.001
Indirect 1.05 [1.02, 1.08] <0.001
Obesity class I Total 1.64 [1.44, 1.88] <0.001 NA
(BMI35 kg/m2) Direct 1.62 [1.42, 1.86] <0.001
Indirect 1.01 [1.00, 1.03] 0.081
Stressful life events Total 1.68 [1.47, 1.93] <0.001 30.5
(16 years) Direct 1.44 [1.25, 1.65] <0.001
Indirect 1.17 [1.13, 1.22] <0.001
Stressful life events Total 1.67 [1.46, 1.91] <0.001 11.1
(<16 years) Direct 1.58 [1.38, 1.81] <0.001
Indirect 1.06 [1.03, 1.09] <0.001
Social support Total 1.67 [1.47, 1.91] <0.001 NA
Direct 1.68 [1.46, 1.93] <0.001
Indirect 1.00 [0.97, 1.02] 0.806
Depression Total 1.67 [1.46, 1.91] <0.001 15.4
Direct 1.54 [1.35, 1.77] <0.001
Indirect 1.08 [1.05, 1.12] <0.001
Anxiety Total 1.67 [1.46, 1.91] <0.001 30.2
Direct 1.43 [1.25, 1.64] <0.001
Indirect 1.17 [1.12, 1.22] <0.001

Note: Boldface type indicates statistical significance (p<0.05)

Abbreviation: OR odds ratio; CI confidence interval
Models are adjusted for age, sex, income, qualification, and ethnicity.
Multimorbidity refers to two or more physical diseases.
Percentage mediated is only provided when the indirect effect is statistically significant.

https://doi.org/10.1371/journal.pone.0191651.t003

loneliness might accrue across the life course in terms of their negative effect on physiological
resilience (and thus, health) [56], the finding of a stronger association between multimorbidity
and loneliness in the youngest age group is somewhat unexpected and it can only be speculated
what underlies this result. It is possible, for instance, that a higher number of chronic diseases
might affect a younger person’s ability to engage in age-related social roles (e.g., spouse, parent,
and/or worker) and social activities and thus act to isolate them. In contrast, older individuals
might have fewer roles or activities and/or had more time to adapt to the inhibiting effects of
several physical illnesses so that only those with a higher number of co-occurring illnesses
experience loneliness. Indeed, the potentially greater detrimental impact of co-occurring

PLOS ONE | https://doi.org/10.1371/journal.pone.0191651 January 24, 2018 9 / 13

 Physical multimorbidity and loneliness

diseases at a younger age might explain why depression and anxiety were important mediators
in the association between multimorbidity and loneliness in those aged under 65 but not in the
oldest age group. The same might also be true when looking at loneliness leading to physical
disease. Specifically, as research has indicated that the prevalence of loneliness might be higher
at both ends of the life span i.e. in adolescence/young adulthood and old age [57], it is possible
that loneliness might have a stronger effect on well-being during an age period where people
are expected to be involved in a variety of personal and work-related relations and where lone-
liness is less common.
This study has several limitations. Physical illnesses were self-reported and were not verified
against other sources of data such as medical records. This might have resulted in misreporting
in some instances especially as evidence suggests that while self-reports of physical illness
mostly accord with doctor’s reports, not all diseases are reported with equal accuracy, and
there might also be age-related differences in the reliability of reports for some diseases [58].
In addition, the survey response rate was moderate (57%) [30]. As research has shown that
lonely individuals trust others less and may be less likely to disclose intimate information for
fear that confidentiality will not be maintained [59], it is possible that they might have been
over-represented among non-responders which might have affected the results (i.e. non-
response bias). Finally, following the lead of an earlier study which used APMS data [33], we
used an item from the SFQ as a measure of loneliness. However, it should be noted that this
item also mentioned ‘isolation’. We were unable therefore to tease apart the association
between loneliness and social isolation in our study despite the fact that they are often studied
separately and may have different effects on health outcomes [60].
In conclusion, this study has shown that physical multimorbidity is associated with
increased odds for loneliness. Given the possible bi-directionality of the association between ill
health and loneliness, this highlights the importance of future longitudinal research to better
specify the association between these phenomena across time, and the potential mechanisms
that might underlie it.

Supporting information
S1 Table. Stressful life events. Events that occurred before the age of 16 are indicated with a
tick mark.
(DOCX)
S2 Table. Lifestyle and other potential mediators in the association between loneliness and
multimorbidity (by age group).
(DOCX)

Acknowledgments
We would like to thank the National Center for Social Research and the University of Leicester
who were the Principal Investigators of this survey. In addition, we would also like to thank
the UK Data Archive and the National Center for Social Research as the data collectors and for
making these data publically available. They bear no responsibility for this analysis or interpre-
tation of this publicly available dataset.

Author Contributions
Conceptualization: Andrew Stickley, Ai Koyanagi.
Formal analysis: Ai Koyanagi.

PLOS ONE | https://doi.org/10.1371/journal.pone.0191651 January 24, 2018 10 / 13

 Physical multimorbidity and loneliness

Writing – original draft: Andrew Stickley.

Writing – review & editing: Andrew Stickley, Ai Koyanagi.

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