Associations between loneliness and perceived social support and outcomes of mental health problems: a systematic review

Associations between loneliness and perceived social support and outcomes of mental health... Background: The adverse effects of loneliness and of poor perceived social support on physical health and mortality are established, but no systematic synthesis is available of their relationship with the outcomes of mental health problems over time. In this systematic review, we aim to examine the evidence on whether loneliness and closely related concepts predict poor outcomes among adults with mental health problems. Methods: We searched six databases and reference lists for longitudinal quantitative studies that examined the relationship between baseline measures of loneliness and poor perceived social support and outcomes at follow up. Thirty-four eligible papers were retrieved. Due to heterogeneity among included studies in clinical populations, predictor measures and outcomes, a narrative synthesis was conducted. Results: We found substantial evidence from prospective studies that people with depression who perceive their social support as poorer have worse outcomes in terms of symptoms, recovery and social functioning. Loneliness has been investigated much less than perceived social support, but there is some evidence that greater loneliness predicts poorer depression outcome. There is also some preliminary evidence of associations between perceived social support and outcomes in schizophrenia, bipolar disorder and anxiety disorders. Conclusions: Loneliness and quality of social support in depression are potential targets for development and testing of interventions, while for other conditions further evidence is needed regarding relationships with outcomes. Keywords: Loneliness, Perceived social support, Outcomes, Mental health problems, Systematic review Background [5, 6]. They are also predictive of development of coron- There is increasing interest in the effects of social rela- ary heart disease and stroke [7], increases in systolic tions on health, and in the service delivery and policy blood pressure [8, 9], and chronic pain [10, 11] in longi- implications of such effects [1]. Loneliness has been a tudinal studies. The effect of loneliness on physical particularly prominent focus in recent research on phys- health may be via biological, psychological and/or behav- ical health [2–4]. For instance, two meta-analytic reviews ioural mechanisms, including physiological functioning, have reported that loneliness and poor social support neuroendocrine effects, gene effects, immune function- are associated with higher mortality rates, and that the ing, perception of stressful events, health behaviours and effect is comparable with some well-established risk sleep quality [2, 12, 13]. In contrast, while loneliness and factors such as obesity, physical inactivity, and smoking lack of social support are well-documented problems among mental health service users [14], they have not been prominent in research, mental health service delivery and * Correspondence: s.johnson@ucl.ac.uk policy. Until recently, there has tended to be less focus on Division of Psychiatry – University College London, 6th Floor, Maple House, the social determinants of mental health than on genetics 149 Tottenham Court Road, London W1T 7NF, England Camden and Islington NHS Foundation Trust, St Pancras Hospital, 4 St and neurobiology, but recent integrated aetiological models, Pancras Way, London NW1 0PE, England © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Wang et al. BMC Psychiatry (2018) 18:156 Page 2 of 16 such as the integrated sociodevelopmental-cognitive model, inform the development of preventive and therapeutic bring social factors into the neuroscientific mainstream, interventions for which there is not as yet an evidence with increasing evidence that such factors need to be base. An important question in evaluating the available included to achieve models of good explanatory value [15– evidence is how far loneliness is conceptually and empir- 17]. An increasing focus on loneliness has also been driven ically distinct from other concepts and measures related by recognition of its high prevalence, and of its wide ran- to social relationships. Loneliness has been shown to be ging impacts on physical health and mental well-being [17]. only moderately correlated with more objectively mea- Despite this increasing recognition of its importance, to sured concepts such as social isolation, social network date no systematic synthesis of the evidence on the rela- size and objective social support received from others tionship between loneliness and the outcomes of mental [30, 31]. However, subjectively rated concepts related to health problems has been published. social relationships are less easy to distinguish clearly Loneliness has been defined as a negative emotional from loneliness [32]. For example, perceived social sup- state that occurs when there is “a discrepancy between… port refers to people’s beliefs about how much support is the desired and achieved patterns of social interaction” potentially available from their relationships and social [18]. Loneliness is sometimes seen as an essentially uni- contacts and about the quality of this support [33, 34]. dimensional concept, sometimes as comprising two di- This is distinct from received social support, a rating of mensions. Weiss [19] proposed a multidimensional how often someone reports receiving particular support- concept of loneliness, categorising loneliness into social ive behaviours [33, 34]. Measures of perceived social and emotional dimensions. Social loneliness derived support assess the quality or adequacy of social support from “the absence of socially integrative relationships”, from a subjective perspective. For instance, the two while emotional loneliness stemmed from the absence of widely used measures, the Multi-dimensional Scale of “a close emotional attachment” [19]. Social loneliness Perceived Social Support (MSPSS) [35] and the Subject- occurs when a person does not have a wider social net- ive Support Subscale of Duke Social Support Index work as desired, which can lead to the feelings of bore- (DSSI) [36], consist of items such as “How often do you dom, exclusion and marginality [19, 20]. In contrast, feel lonely?”, “Can you talk about your deepest prob- emotional loneliness occurs when someone is missing an lems?”, “I have friends with whom I can share joys and intimate relationship, which can result in distress and ap- sorrows”, which have a high degree of overlap with lone- prehension [19, 20]. Psychometrically robust self-report liness measures. Likewise, measures of confiding rela- measures of loneliness have been developed and used ex- tionships assess the extent to which people feel close to tensively in research on physical health and on older and able to talk intimately with other people [37, 38]. people, including the University of California at Los Studies have found large negative correlations between Angeles (UCLA) Loneliness Scale [21] and the de loneliness and perceived social support [39–42]. Thus Jong-Gierveld Loneliness Scale [22]. Feelings of loneliness these concepts resemble loneliness as subjective evalua- are more prevalent among people with mental illness than tions of the quality and impact of social relationships: in the general population [23, 24]. In a study of older given this conceptual overlap, this paper includes them adults with major depression, dysthymia, or minor depres- along with loneliness. sion, 83% of the respondents reported loneliness and 38% Three previous systematic reviews have explored the reported severe loneliness [25]. By comparison, only 32% relationship between social relations and depression in of non-depressed elderly people were lonely and 4% se- general population [43, 44], or older adults [45], but in- verely lonely using the same loneliness scale [26]. In a cluded both cross-sectional and prospective studies. One comparison of people with psychosis and a general popu- further review looked at the relationship between social lation sample with similar demographic characteristics, networks and support and early psychosis in people with the prevalence of loneliness among people with psychosis first episode psychosis and in general population sam- was 79.9% compared with 35% in the general population ples, but included no prospective studies [46]. To our [27]. For people with depression, cross-sectional studies knowledge, there is no systematic review which summa- have found up to 40% of respondents feeling lonely most rises and synthesises the evidence regarding the relation- of the time [28], with a tenfold increase in the odds of be- ship between loneliness and perceived social support ing lonely compared to the general population [29]. and the course of existing mental health problems, and Given the high prevalence of loneliness among people which includes only prospective studies, from which in- with mental health problems and the evidence for its ferences about the direction of causation may be drawn. harmful effects in other populations, good quality evi- Our review will fill this gap, and will provide useful evi- dence is needed on its impact on recovery from mental dence about how far and in what context loneliness and health problems and on the health and social function- perceived social support may influence mental health re- ing of mental health service users. This has potential to covery. Thus the aim of the current paper is to Wang et al. BMC Psychiatry (2018) 18:156 Page 3 of 16 synthesise the available evidence as to whether higher outcomes. Studies in which any of the following out- levels of loneliness and poorer perceived social support comes were measured at follow-up were eligible for have an adverse effect on outcomes in adults of all ages inclusion: with existing mental health problems. 1) Relapse: recurrent episodes following recovery at Methods baseline of mental illness meeting the criteria of A systematic review was conducted of the scientific litera- DSM or ICD, or of other reliable and valid ture addressing the question of whether loneliness and low instruments such as the Center for Epidemiologic perceived social support are associated longitudinally with Studies Depression Scale (CES-D), and proxy poorer outcomes among adults of all ages with a range of measures of acute relapse such as admission to mental health problems. The review’s protocol was regis- psychiatric hospital/crisis services/acute mental tered on PROSPERO, which is an international database of health services. prospective systematic reviews with health related out- 2) Measures of functioning or of recovery: recovery of comes (registration number: CRD42015014784) [47]. function, social functioning, self-rated recovery, quality of life, and disability. Inclusion criteria 3) Symptom severity: level of symptoms, symptom Types of study: The review included longitudinal studies improvement or deterioration. in which the relationship between baseline measures of 4) Global outcome: overall outcome rating combining loneliness and poor perceived social support and out- different aspects of mental health and functioning, comes at follow up was examined using quantitative such as the Health of the Nation Outcome Scales measures. (HoNOS). Participants: Participants in the included studies were adults with mental illnesses, specifically schizophrenia Search strategy and schizoaffective disorder, psychosis in general, de- A systematic search of the following six electronic data- pression, bipolar disorder, and anxiety disorders. Clinical bases was undertaken: Medline, PsycINFO, Embase, populations were included however diagnosis was made, Web of Science, CINAHL and Cochrane Library (1891 for example clinical diagnoses, ratings according to the to April 2016). No language and publication period re- criteria of the Diagnostic and Statistical Manual of Men- strictions were applied. Search terms for loneliness and re- tal Disorders (DSM) or the International Classification lated concepts were combined with terms for mental of Diseases (ICD), or use of reliable and valid instru- disorders and outcomes. Searches were conducted using ments such as the Mini-International Neuropsychiatric both subject headings (MeSH terms) and text words within Interview (M.I.N.I.). We excluded studies with samples title and abstract. Search terms were adapted as required of children under 16 years old, people with intellectual for different databases (for full details, see Additional file 1). disabilities or organic mental disorders including demen- The search terms used in Medline are as follows: tia, or cohorts assembled on the basis of a primary phys- ical illness diagnosis. 1) Loneliness: loneliness [MeSH] OR loneliness OR Exposure variables: Included studies used quantitative lonely OR social support adj5 (subjective or measures of loneliness or of related concepts that in- personal or perceived or quality) OR confiding volve a subjective rather than objective appraisal of so- relationship* cial relationships, such as perceived social support or 2) Mental disorders: mental disorders [MeSH]. exp. confiding relationships. Concepts based on objective rat- OR mental OR psychiatr* OR schizo* OR psychosis ings of the size and functioning of social networks, such OR psychotic OR depress* OR mania* OR manic as social isolation and social network size, were ex- OR bipolar adj5 (disorder or disease or illness) OR cluded. Social capital was also excluded as it relates to anxiety disorders [MeSH]. exp. characteristics of society or communities as a whole as 3) Outcomes: prognosis [MeSH] OR outcome* OR well as individuals’ appraisal of their relationships, and is recurren* OR relapse OR admission OR conceptually distinct from loneliness [32]. We included hospitali?ation OR crisis OR admitted OR detained studies only if exposure variables assessed subjective ap- OR detention OR recovery of function [MeSH] OR praisal of overall social connectedness, rather than the “social functioning” OR “self-rated recovery” OR quality of specific relationships: therefore, measures of “quality of life” OR “symptom severity” OR support from partner and quality of a specific significant disability relationship were excluded. Outcomes: The review included a wide variety of out- Apart from outcome terms, we searched “onset” and comes, ranging from clinical outcomes to functioning related terms as searches were conducted simultaneously Wang et al. BMC Psychiatry (2018) 18:156 Page 4 of 16 for this and a companion systematic review on loneliness narrative synthesis of results as the anticipated hetero- as a risk factor for the onset of psychiatric disorders in geneity of included studies, for example in samples, pre- the general population. Reference lists of studies identi- dictor measures and outcomes, made a meta-analysis fied through the electronic search for inclusion in the re- inappropriate. The main results have been stratified by view and of review articles were manually searched for type of mental health problem investigated and tables further relevant studies. Relevant studies reported in dis- and text were used to summarise the data. sertations, conference reports or other sources other than published journals were searched using the free text Results and keyword searches from the following two sources: Literature search Zetoc (indexing and abstracting database of conference Our initial database search retrieved 13,076 records (see proceedings) and OpenGrey (system for information on Fig. 1). After excluding duplicates and screening titles grey literature in Europe). When necessary and possible, and abstracts to exclude obviously irrelevant papers, 797 we sent emails to authors to request full text or clarify full-text articles were assessed for eligibility. 734 studies some uncertainties. were excluded because: i) they were not longitudinal Selection of studies for inclusion in the review was quantitative studies; ii) they assessed a form of social re- made independently by two reviewers (J.W. & F.M.). Ti- lationships conceptually distinct from loneliness or per- tles of all identified studies were screened. The abstracts ceived social support; iii) they analysed the relationship of potentially relevant studies were read; the full text of between change scores in loneliness and outcome vari- studies still considered potentially relevant was then re- ables, rather than baseline loneliness as a predictor of trieved and read. All studies included by one assessor outcome; or iv) they investigated a sample consisting of were confirmed by the other reviewer to check adher- children under 16 years old or of people with primary ence to inclusion criteria in study selection. 800 studies diagnoses of drug and alcohol disorders, personality dis- excluded by one assessor were checked by the other re- orders, post-traumatic stress disorder (PTSD), learning viewer to establish reliability of our study selection. The disabilities or organic mental disorders, or of people re- agreement between reviewers was higher than 99%. cruited as having specific physical illnesses. Twenty-two Queries about inclusion/exclusion were resolved through further papers were retrieved by hand-searching the ref- discussion with a third reviewer (S.J.). erence lists of the papers already identified. Of the resulting 85 studies, 34 articles about outcomes of men- Data extraction, quality assessment and synthesis tal disorders among people with existing mental health A structured template was developed to extract relevant problems were included in this review. The other 51 pa- data from eligible papers. Two review authors (J.W. & pers will be reported in a companion systematic review F.M.) independently extracted data and assessed their regarding the relationship between loneliness and onset methodological quality. Extracted data and quality as- of mental health problems in the general population. sessment scores were checked by a second reviewer for The search results are reported as a Prisma diagram in 20% of papers. Disagreements between the two assessors the Fig. 1. were resolved through discussion with a third review au- thor (S.J.). The methodological quality of each study in- Eligible papers cluded in the review was assessed using a standard form The 34 eligible papers were from seven countries, in- adapted from the Mixed Methods Appraisal Tool cluding 23 from North America, 10 from Europe and (MMAT) – Version 2011 [48]. The MMAT has been de- one from Israel. These papers consisted of 23 studies signed for appraisal of the methodological quality for with samples of people with depression, two focusing on qualitative, quantitative and mixed methods studies. For schizophrenia or schizoaffective disorders, four on bipo- quantitative studies it includes criteria relevant to rando- lar disorder, and three on anxiety disorders. Two further mised controlled, non-randomised, and descriptive stud- studies included people with a mixture of mental health ies. For the purposes of our review, we used the criteria problems (Table 1). Only two studies directly assessed for the quantitative non-randomised domain (Cohort loneliness, and most of the studies used various scales to study version). As there are four criteria for this domain measure perceived social support. Nearly half of in- following two screening questions, the overall quality cluded papers studied symptom severity as an outcome, score was presented using descriptors *, **, ***, and ****, a third of the papers assessed recovery/remission, and a ranging from * (one criterion met) to **** (all criteria third of the papers included other outcomes such as met). The four criteria related to selection bias, meas- quality of life, disability pension qualification, functional urement quality, adjustment for confounders, and per- impairment or life satisfaction. The sample sizes of six centage of complete outcome data/response rate/ studies in our review exceeded 400, 22 were between follow-up rate (see Additional file 2). We conducted a 100 and 400, and six were less than 100. Six studies had Wang et al. BMC Psychiatry (2018) 18:156 Page 5 of 16 Fig. 1 Studies selection flowchart short length of follow-up (less than one year), 23 follow- significant predictor of higher depressive symptom se- ing up the cohorts for one to two years, and five for over verity at follow-ups (Table 2). Nine of these eleven pa- two years. With regard to quality assessment, five studies pers conducted multivariable analyses including were assigned a maximum score of four (****) as their adjusting for baseline depression severity. In eight of overall quality scores, 16 studies had a score of three these nine papers, the relationship between baseline (***) and 13 papers had two (**) according to the loneliness and depressive symptom outcome remained appraisal criteria of MMAT. Most studies had lower significant. For example, among the three studies with quality assessment ratings because they did not report high quality scores (****), Blazer and colleagues [49] and the percentage of complete outcome data, response rate Brugha and colleagues [50] followed cohorts of adults or follow-up rate (for full details, see Additional file 2). with depression in America and the UK respectively. They reported that poorer subjective social support at Depression baseline was predictive of poorer outcomes at follow-up, Among the 23 papers with samples of people with de- outcomes including poorer life satisfaction (beta = 0.10, pression, 13 studies assessed depression severity as an B = 0.37), worse depressive symptoms (beta = 0.10, B = outcome. Eleven of these found that poorer perceived 0.30) [49], and more severe psychiatric status (regression social support or greater loneliness at baseline was a coefficient = − 1.46) [50]. In the third study rated as high Wang et al. BMC Psychiatry (2018) 18:156 Page 6 of 16 Table 1 Summary of characteristics of included studies Condition studied Predictor variable Outcomes Sample size range (median) Length of follow-up Follow-up rate range (median) Quality score Depression (n = 23) Perceived social support (n = 22) Symptom severity (n = 13) 66–604 (239) Short (n =4) 60.6–100% (81.9%) **** (n =4) Loneliness (n =1) Recovery/remission (n =7) Medium (n = 14) *** (n = 11) Functional outcomes (n =5) Long (n =5) ** (n =8) Schizophrenia/schizoaffective Perceived social support (n = 2) Functional outcomes (n = 2) 139–148 (143.5) Medium (n = 2) 71.9–100% (86.0%) *** (n =1) disorders (n =2) ** (n =1) Bipolar disorder (n = 4) Perceived social support (n = 4) Symptom severity (n =3) 42–173 (55.5) Short (n =1) 71.1–100% (86.4%) *** (n =2) Recovery/remission (n =2) Medium (n = 3) ** (n =2) Functional outcomes (n =2) Anxiety disorders (n = 3) Perceived social support (n = 3) Symptom severity (n =1) 134–1004 (1004) Short (n =1) 80–87% (81.0%) **** (n =1) Recovery/remission (n =1) Medium (n =2) *** (n =1) Functional outcomes (n =1) ** (n =1) Mixed samples with various mental Perceived social support (n =1) Symptom severity (n =1) 352–743 (547.5) Medium (n = 2) 79.9–84.4% (82.2%) *** (n =1) health problems (n = 2) Loneliness (n =1) Functional outcomes (n =1) ** (n =1) Length of follow-up: Short = < 1 year; Medium = 1–2 years; Long = > 2 years. ** = two criteria of MMAT met. *** = three criteria of MMAT met. **** = all criteria of MMAT met Wang et al. BMC Psychiatry (2018) 18:156 Page 7 of 16 Table 2 Summary of findings on depression Reference Predictor Outcome variable Results (++ < 0·05 adjusted; + < 0·05 unadjusted; − variable non-significant) Hybels et al. (2016) [79] Perceived social Trajectory class ++ Patients in the persistent moderate depression class had support (quick recovery, lower levels of baseline subjective social support compared slow recovery, with patients in the quick recovery class (OR (95%CI) = 0.91 persistent moderate, (0.83, 0.98)). Patients in the persistent high depression class and persistent high) had lower levels of baseline subjective social support compared with those in the quick recovery class (OR (95%CI) = 0.83 (0.75, 0.92)) Holvast et al. (2015) [25] Loneliness Symptom severity; ++ In the fully adjusted model, a 1-point higher baseline Remission ++ loneliness score predicted a 0·61-point higher depressive symptom severity score at follow-up (Beta = 0.61, 95% CI 0.12–1.11, p = 0.02). Logistic regression analysis showed that while adjusting for social network size and potential confounders, the very severely lonely respondents were less likely to achieve remission from their depressive disorder compared with the non-lonely respondents (OR = 0.25, 95% CI 0.08–0.80, p = 0.02). Holma et al. (2012) [54] Perceived social Disability pensions + Lower perceived social support at baseline predicted greater support likelihood of being granted a disability pension over 5 year follow-up on univariate analysis (p = 0.031), but not significant in multivariate analyses where the outcome was the interval time to the date the pension was granted Backs-Dermott et al. (2010) [80] Perceived social Relapse versus stable ++ Lower perceived social support from a significant other support remitted (standardized discriminant function coefficient 0.48) and lower perceived social support from friends (standardized coefficient 0.35) at baseline predicted greater likelihood of depressive relapse at one-year follow-up. The Discriminant Function Analysis was significant, Wilk’s Lambda = 0.69, x (5) = 16.35, p = 0.006 Bosworth et al. (2008) [81] Perceived social Depression severity ++ Poorer subjective social support was a significant predictor support of more severe depression at 12 months. Standardized beta = − 0.13, p = 0.05 Rytsala et al. (2007) [55] Perceived social Work disability + Lower perceived social support at 6 month was a significant support allowances predictor of greater likelihood of being granted disability allowances at 18 months (F = 6.3, p = 0.013), but not significant in multivariate analysis Rytsala et al. (2006) [56] Perceived social Functional disability; ++ Lower perceived social support at baseline was a significant support Social and work ++ predictor of more severe functional disability at 6 months adjustment; − (B = 0.232, β = 0.210, p = 0.002, 95% CI 0.084 to 0.379), and Days spent ill in poorer social and work adjustment at 6 months (B = − 0.008, bed or not β = − 0.222, p = 0.001, 95% CI -0.013 to − 0.003). Lower perceived social support at 6 months was one of the most significant factors predicting more severe functional disability at 18 months (B = 0.240, β = 0.215, p = 0.002, 95% CI 0.088 to 0.393), and poorer social and work adjustment at 18 months (B = − 0.011, β = − 0.303, p‹0.001, 95% CI -0.015 to − 0.006). But perceived social support did not predict any days spent ill in bed or not Leskela et al. (2006) [51] Perceived social Severity of depression + Lower perceived social support at 6 months predicted support more severe depression at 18 months in original zero-order correlation (r = − 0.392, p < 0.001) and within-group standardised correlation (r = − 0.230, p = 0.001) among all patients, but not significant in multivariate analysis. In full remission group at 6 months (n = 67), lower perceived social support at 6 months predicted higher level of depressive symptoms at 18 months in multivariate analysis (r = − 0.321, p = 0.012) Steffens et al. (2005) [82] Perceived social Severity of depression ++ Lower subjective social support at baseline predicted more support severe depression over time (estimate − 0.5641, p = 0.0002) Ezquiaga et al. (2004) [83] Perceived social Episode remission – Higher perceived social support at baseline did not predict support remission at 12 months in univariate analysis (p = 0.33), and it was not included in multivariate analysis Wang et al. BMC Psychiatry (2018) 18:156 Page 8 of 16 Table 2 Summary of findings on depression (Continued) Reference Predictor Outcome variable Results (++ < 0·05 adjusted; + < 0·05 unadjusted; − variable non-significant) Reference Predictor Outcome variable Results (++ < 0·05 adjusted; + < 0·05 unadjusted; − variable non-significant) Gasto et al. (2003) [84] Perceived social Severity of residual ++ Lower subjective social support at baseline predicted support symptoms higher intensity of residual symptoms at 9 months in remitters (standardized β = 0.41, p < 0.001) Bosworth et al. (2002) [53] Perceived social Time-to-remission ++ Lower subjective social support at baseline (Hazard support Ratio = 0.47, 95% CI: 0.31–0.71, p = 0.003) was a significant predictor of longer time to remission Bosworth et al. (2002) [52] Perceived social Remission ++ Lower baseline levels of subjective social support support (OR = 1.21, 95% CI: 1.09–1.35, p < 0.001) predicted poorer recovery one year later Triesch (2002) [85] Perceived social Severity of depressive − Lower perceived social support at baseline did not support symptoms; − predict more severe depression (β = − 0.17) or poorer Quality of life quality of life (β = − 0.12) at 3 months Hays et al. (2001) [57] Perceived social Activities of daily living ++ There was modest support for hypothesis that baseline support subjective social support predicted functional declines at 1 year. There was partial support for hypothesis that the buffering effects of social support against functional decline would be strongest among the most severely depressed patients Oxman and Hull (2001) [86] Perceived social Depression severity ++ Greater perceived social support predicted subsequent support decreases in depression among participants randomly assigned to placebo group (6-week depression − 0.18, p < 0.05; 11-week depression − 0.22, p < 0.05), but not significant among paroxetine group or Problem-Solving Treatment for Primary Care group Brummett et al. (2000) [87] Perceived social Depressive symptoms – Higher levels of received support at baseline significantly support predicted decreases in depressive symptoms at both 6 months and 1 year, whereas subjective support did not significantly predict changes in depressive symptoms at either point in time Sherbourne et al. (1995) [88] Perceived social Number of depressive ++ Decreased number of depressive symptoms between support symptoms baseline and 2-year follow-up was predicted by social support at baseline (standardised regression coefficients = 0.12, zero-order Pearson product-moment correlations = 0.16, p < 0.05). Among the subset of patients who had current depressive disorder at baseline, perceived social support was not significantly related to remission. Among patients without current depressive disorder at baseline (subthreshold depression), patients with higher level of perceived social support were less likely to experience a new depressive episode during 2-year period: odds ratio = 0.96 (CI:0.95, 0.98) Blazer et al. (1992) [49] Perceived social Decreased life satisfaction ++ Impaired subjective support at baseline was predictive support symptoms; of poorer outcome at 12-month follow-up in both models: Endogenous symptoms decreased life satisfaction symptoms (b = 0.10, B = 0.37, p ≤ 0.001), endogenous symptoms (b = 0.10, B = 0.30, p≤ 0.01) Blazer et al. (1991) [89] Perceived social Depressive symptoms + Intercorrelation between social support at baseline and support depression score at 6 months: − 0.41, p < 0.001. Intercorrelation between social support at baseline and depression score at 12 months: − 0.34, p < 0.001 Brugha et al. (1990) [50] Perceived social Symptom severity ++ After controlling for the two significant clinical predictors, support a significant main effect was found in total sample for lower satisfaction with support at baseline on more severe psychiatric status at 4 months (regression coefficient = − 1.46, p < 0.05) Wang et al. BMC Psychiatry (2018) 18:156 Page 9 of 16 Table 2 Summary of findings on depression (Continued) Reference Predictor Outcome variable Results (++ < 0·05 adjusted; + < 0·05 unadjusted; − variable non-significant) George et al. (1989) [90] Perceived social Depressive symptoms ++ Impaired subjective social support at baseline is a support significant predictor of higher numbers of CES-D symptoms at follow-up (b = 8.88, B = 0.20, p ≤ 0.05) Krantz and Moos (1988) [91] Perceived social Remitted, partially + Lower quality of relationships at baseline predicted support remitted, and poorer remission status after 1 year (χ = 10.21, p < 0.01) nonremitted quality, Leskela and colleagues [51] assessed adults with later (OR = 1.21, 95% CI 1.09–1.35) [52], and of lon- major depressive disorder and found that lower per- ger time-to-remission in a study of initially de- ceived social support six months after initial assessment pressed elderly individuals (Hazard Ratio = 0.47, 95% predicted more severe depression at 18 months among CI 0.31–0.71) [53]. However, none of the seven stud- all participants, although this relationship only remained ies had high quality scores (****), with five receiving significant in multivariable analysis for the group who medium (***), and two low scores (**). had remitted following initial assessment (r = − 0.321). With regard to functional outcomes (five articles), The only study using loneliness as a predictor of depres- three studies have found that lower perceived social sup- sion outcomes was conducted by Holvast and colleagues port at baseline was a significant predictor of greater [25] among Dutch older adults. They found that a likelihood of being granted disability pensions during 1-point higher loneliness score was predictive of a the follow-up period (no effect size reported) [54, 55] 0.61-point higher depressive symptom severity score at and of more severe functional disability (beta 0.210 to follow-up (Beta = 0.61, 95% CI 0.12–1.11). For studies 0.215, 95% CI 0.084–0.393) [56]. There is also evidence which reported beta as the effect size, beta ranged from that greater perceived social support predicted better so- 0.10 to 0.61. Among the 13 studies, three articles had cial and work adjustment (beta − 0.222 to − 0.303, 95% high quality (****), four had medium quality (***), and CI -0.013 to − 0.006) [56], and buffered functional de- the other six received low quality ratings (**). However, clines in performance on activities of daily living (no ef- no obvious relationship was found between study quality fect size reported) [57]. However, after adjustment for and whether results were significant. potential confounders only two [56, 57] of the five stud- Six out of seven articles which used recovery/re- ies had significant results. mission of depression as their outcomes reported lower perceived social support or higher loneliness at baseline as a significant predictor of lower rates Schizophrenia/schizoaffective disorders of recovery/remission at follow-up. Three of the Two studies assessed patients with schizophrenia or seven studies adjusted for baseline depression sever- schizoaffective disorders to identify psychosocial predic- ity, and all of them reported significant results. For tors of health-related quality of life and functional out- example, in the study of Holvast et al. [25], the comes (Table 3). Ritsner and colleagues [58] followed a lonely respondents at baseline were reported to be sample of inpatients with schizophrenia or schizoaffec- less likely to achieve remission from their depressive tive disorders for 16 months and found that greater sup- disorder at follow-up compared with the non-lonely port from friends at baseline predicted better satisfaction respondents (OR = 0.25, 95% CI 0.08–0.80). Similarly, with life quality after 16 months (accounted for 2.9% of poorer perceived social support at baseline was a quality of life index scores at follow up examination). In significant predictor of poorer recovery one year an American study, greater perceived social support was Table 3 Summary of findings on schizophrenia and schizoaffective disorders Reference Predictor variable Outcome variable Results (++ < 0·05 adjusted; + < 0·05 unadjusted; − non-significant) Ritsner et al. (2006) [58] Perceived social support Quality of life ++ Higher friend support at baseline predicted better satisfaction with life quality after 16 months (accounted for 2.9% of quality of life index scores at follow up examination) Brekke et al. (2005) [59] Perceived social support Global functional outcome − Higher social support did not significantly predict (work, social functioning, and better global functional outcome at 12 months independent living); (p < 0.10). But social support became a much Social functioning domain ++ stronger and statistically significant predictor of social functioning domain Wang et al. BMC Psychiatry (2018) 18:156 Page 10 of 16 a strong predictor of better scores on a social function- recurrence, the other three had adjustment for baseline ing domain (no effect size reported), although it did not score on the outcome measure. predict the global functioning score (a composite of vo- cational and social functioning, and independent living) Anxiety disorders [59].However, neither of these studies adjusted for the The three studies of patients with anxiety disorders all re- outcome variable baseline scores. ported significant associations between perceived social support at baseline and outcomes at follow-up (Table 5). Bipolar disorder Two studies included people with diagnoses of generalised We found four papers that studied adults with a diagno- anxiety disorder, panic disorder, social anxiety disorder or sis of bipolar disorder (Table 4). The evidence regarding post-traumatic stress disorder. One study found that lower depressive symptoms was consistent and showed that perceived social support was predictive of more severe lower perceived social support predicted greater depres- anxiety (beta = − 0.15, CI [− 0.30, − 0.06], Ratios 8.85%) sion over time (beta − 0.14 to − 0.25, regression coeffi- and depressive symptoms (beta = − 0.16, CI [− 0.28, − cient − 1.33) [60–62]. Lower perceived support was also 0.08], Ratios 10.51%) at subsequent time points [33], and found to be a significant predictor of greater impairment the other one found that greater perceived social support in functioning (beta − 0.14 to − 0.67) [60, 61], and longer predicted a higher rate of remission at 6-month follow-up time to recovery (no effect size reported) [62]. Among (OR = 1.38, 95% CI Wald 1.09–1.75) [64]. In a study of remitted patients with prior diagnosis of bipolar I dis- older adults with generalised anxiety disorder, Shrestha et order, greater perceived social support reduced risk of al. [65] found that individuals with greater perceived social recurrence of any type (depressive or manic) at one year support at baseline reported greater average quality of life (OR = 0.92, 95% CI 0.85–0.99) [63]. With regard to se- over time (beta = 0.41), albeit without adjustment for the verity of manic symptoms, however, the results were not outcome variable baseline score. so consistent. In one study lower perceived support sig- nificantly predicted more severe manic symptoms on Mixed samples with various mental health problems follow-up assessment (beta = − 0.32) [61], but in other Two studies examined mixed samples of people with a two studies it was not linked with subsequent manic variety of diagnoses (Table 6). Beljouw et al. [66]ana- symptomatology [60, 62]. Apart from the study of lysed data from primary care patients with current anxiety Table 4 Summary of findings on bipolar disorder Reference Predictor variable Outcome variable Results (++ < 0·05 adjusted; + < 0·05 unadjusted; − non-significant) Koenders et al. (2015) [60] Perceived social Depressive symptomatology; ++ Lower perceived support predicted more depression support Depression related functional ++ related functional impairment during the subsequent impairment; 3 months (β (SE) = − 0.14 (0.03), p < 0.001), and with Manic symptomatology; more depressive symptomatology at the subsequent Manic related functional time point (β (SE) = − 0.14 (0.04), p = 0.002). No significant impairment associations between perceived social support and manic symptoms and impairment were observed Cohen et al. (2004) [63] Perceived social Recurrence ++ After controlling for clinical variables, lower social support support of any kind significantly predicted recurrence of any type at one year (β (SE) = − 0.09 (0.04), p = 0.03, OR = 0.92, 95% CI 0.85–0.99) Daniels (2000) [61] Perceived social Depressive symptomatology; ++ Lower perceived support was a significant predictor of support Manic symptomatology; ++ more severe depressive symptomatology after controlling 2 2 Functional impairment ++ for initial levels of depression (R = 0.67, F = 34.15, ΔR = 0.05, ΔF = 5.24, beta = − 0.25). Lower perceived support significantly predicted more severe manic symptomatology over three 2 2 months (R = 0.18, F = 3.74, ΔR = 0.10, ΔF = 4.18, beta = − 0.32). Lower perceived social support significantly predicted impairment in functioning in the participants who completed their life charts for 90 consecutive days, after controlling for initial levels of 2 2 functional impairment (R = 0.44, F = 5.48, ΔR = 0.41, ΔF = 10.22, beta = − 0.67). Johnson et al. (1999) [62] Perceived social Time to recovery; ++ Lower social support was a significant predictor of longer time support Severity of depressive ++ to recovery in Cox regression survival analyses (χ2 (1, N = 52) symptoms; − change = 5.89, one-tailed p < 0.01). In hierarchical multiple Severity of manic symptoms regression analyses, low social support predicted higher depression over time (regression coefficient = − 1.33, p < 0.01, R change = 0.07, F change = 11.70). Social support did not have significant impact on mania score at 6-month follow-up Wang et al. BMC Psychiatry (2018) 18:156 Page 11 of 16 Table 5 Summary of findings on anxiety disorders Reference Predictor variable Outcome variable Results (++ < 0·05 adjusted; + < 0·05 unadjusted; − non-significant) Jakubovski and Bloch (2016) [64] Perceived social Remission; ++ Generalised anxiety disorder: Greater amount of social support Response (a reduction ++ support predicted a higher rate of remission (OR = 1.38, of at least 40% symptoms 95% CI Wald 1.09–1.75, p = 0.0067) and a greater rate of at 6 months) response (OR = 1.33, 95% CI Wald 1.10–1.62, p = 0.0040) at 6-month follow-up. Social anxiety disorder: Greater amount of social support predicted a higher rate of remission (OR = 1.716, 95% CI Wald 1.028–2.867, p = 0.0391) at 6-month follow-up, but social support did not predict response. Social support did not predict remission or response for panic disorder or post-traumatic stress disorder Shrestha et al. (2015) [65] Perceived social Quality of life ++ Main effect of social support was significant such that support those with higher baseline social support reported higher average quality of life over time (b (SE) = 0.41 (0.08), p < 0.001) Dour et al. (2014) [33] Perceived social Anxiety symptoms; ++ Direct effects: Relations between perceived social support Depressive symptoms ++ support and depression were bidirectional at all follow-ups, whereas they were unidirectional between perceived social support and anxiety at 6- and 12-month follow-ups. Indirect effects: Intervention led to changes in 6- and/or 12-month perceived social support, that in turn led to subsequent changes in 18-month depression (b = − 0.16, CI [− 0.28, − 0.08], Ratios 10.51%) and anxiety (b = − 0.15, CI [− 0.30, − 0.06], Ratios 8.85%) or depressive disorders, and found that greater loneliness Discussion at baseline was predictive of more severe depressive (beta Main findings = 0.89) or anxiety symptoms (beta = 0.40) at 1-year We found 34 studies that reported quantitatively on the follow-up. However, after adjustment for baseline severity longitudinal relationship between perceived social sup- of depression or anxiety, only the relationship with de- port/loneliness at baseline and various outcomes of pression severity remained significant (beta = 0.39). Fleury mental illness at follow-up. Although substantial hetero- and colleagues [67] conducted a study among individuals geneity exists in the identified articles, some generalisa- with severe mental health problems including schizophre- tions can be made. There is substantial evidence that nia and other psychotic disorders and severe mood disor- less perceived social support at baseline tends to predict ders. They reported that greater perceived social support greater symptom severity, poorer recovery/remission was significantly predictive of higher subjective quality of and worse functional outcomes at follow-up among life at 18 months (beta 0.136 to 0.196, 95% CI 0.255 to people with depression, and preliminary evidence of a 3.410). However, adjustments for baseline measures in- similar relationship for people with bipolar disorder, or cluded functional ability in the community and diagnosis, anxiety disorders. There is also some evidence that but not baseline quality of life. greater loneliness is associated with more severe Table 6 Summary of findings on mixed samples with various mental health problems Reference Predictor variable Outcome variable Results (++ < 0·05 adjusted; + < 0·05 unadjusted; − non-significant) Fleury et al. (2013) [67] Perceived social Subjective quality ++ Social support variables at baseline accounted for 7.9% of support of life quality of life at 18-month follow-up. Among social support dimensions, higher perception of availability of social integration (β = 0.196, t = 3.472, p = 0.001, 95% CI [0.942, 3.410]) and reassurance of worth supports (β = 0.136, t = 2.397, p = 0.017, 95% CI [0.255, 2.597]) at baseline predicted better quality of life at 18-month follow-up Van Beljouw et al. (2010) [66] Loneliness Severity of ++ A higher symptom severity in depression at 1-year follow-up was depression; + predicted by more loneliness at baseline in both multilevel univariate Severity of anxiety linear regression analyses (β = 0.89, SE = 0.17, p < 0.001) and multilevel multivariate linear regression analyses (β = 0.39, SE = 0.16, p < 0.05). Positive associations were found between more symptom severity in anxiety at 1-year follow-up and loneliness at baseline by multilevel univariate linear regression analyses (β = 0.40, SE = 0.12, p < 0.01) (but not significant in multivariate analyses) Wang et al. BMC Psychiatry (2018) 18:156 Page 12 of 16 depression and anxiety symptoms and poorer remission although they all measure individuals’ subjective ap- from depression. An important consideration in inter- praisal of adequacy or impact of their relationships ra- preting findings is that depression is very likely to make ther than objective or structural social support. Both people more likely to appraise their social support as in- loneliness studies used a published measure of loneliness adequate and to feel emotionally lonely. However, a per- with well-established psychometric properties, but this sistent effect on outcomes is found in many studies with review shows that knowledge about the relationship be- adjustment for baseline depression severity. With regard tween loneliness and outcomes of mental health prob- to schizophrenia/schizoaffective disorders, only func- lems is still very limited. Finally, the studies in our tional outcomes have been studied and the small review had sample sizes ranging from 42 to 1004, and amount of available evidence suggests that greater per- diverse follow-up periods from a few months to ten ceived social support is predictive of better subjective years. The sample size of most studies is under 400 with quality of life and social functioning. This review, to our less than 100 participants in six articles. However, the knowledge, is the first to systematically examine longitu- consistency of positive findings from included studies, ir- dinal studies regarding the relationship between loneli- respective of their sample size, provides some confidence ness and closely related concepts and outcomes for that studies were not underpowered. adults of all ages and all types of mental illness. Other limitations of this review relate to the search strategy. Although our literature search was conducted Strengths and limitations of the included studies and of in six databases and a variety of search terms were ap- this review plied, the search might not be exhaustive. Some relevant Generally, the quality of included studies is acceptable studies may have been missed if they did not use “sub- and most studies were assigned at least *** as their over- jective or personal or perceived or quality” five or fewer all quality scores in accordance with the methodological words apart from “social support”. Some very old papers quality criteria of MMAT. However, some methodo- might not be indexed in electronic databases, and thus logical issues in the published literature may limit what cannot be searched. Eligible studies are only from seven can be inferred from the studies. Many studies did not countries and most of them were conducted in North have comprehensive information about percentage of America. Very few papers in other languages were re- complete outcome data, baseline response rate, or trieved and none of them could be included in our re- follow-up rate, resulting in lower quality assessment rat- view, although we did search for them and read their ings. We did assess whether studies adjusted for baseline abstracts. It is also worth noting that the extent of any measurements on the outcomes. Some did not, increas- reporting bias is uncertain as studies which did not find ing uncertainty about the direction of causation (al- a positive result might not be published. Another limita- though if the baseline outcome measure which included tion refers to the scope of our review. We restricted the random errors was introduced as a covariate, regression search to the most common mental disorders, including to the mean might lead to biased results according to schizophrenia and schizoaffective disorder, psychosis in Lord’s paradox [68]). A large majority of the 23 studies general, depression, bipolar disorder, and anxiety disor- that did adjust for baseline outcome measures still found ders. The associations between loneliness and perceived loneliness/perceived social support to be predictive of social support and other mental health problems need outcomes. This suggests that there is a real effect of further investigation. Additionally, we focused on one loneliness/lack of social support on outcomes. However, direction of causation only: the effect of baseline loneli- it is likely that the relationship can be a circular one, ness and poor perceived social support on mental health with loneliness/lack of social support resulting in more outcomes at follow up. Psychiatric symptoms probably severe symptoms, and more severe symptoms exacerbat- also influence loneliness and perceived social support, ing loneliness/lack of social support. but this was not the research question on which we fo- The consistency of findings across a variety of settings, cused in this review. measures of the exposure, and population groups in- creases confidence in the generalisability of the review’s Research implications findings. The retrieved articles encompassed varying Most studies included in our review focused on depres- populations including older and younger groups, and sion, with other types of mental health problems repre- people recruited in primary care, inpatient and out- sented by fewer than five studies each. Nevertheless, patient settings, and were carried out around the world. some significant relationships have been found between Most studies of perceived social support used loneliness and/or perceived social support and outcomes well-developed scales where psychometric properties of those mental disorders. Gayer-Anderson and Morgan have been established. The measures used varied regard- [46] systematically examined evidence on social net- ing the dimensions and types of social support assessed, works and social support in early psychosis. They found Wang et al. BMC Psychiatry (2018) 18:156 Page 13 of 16 some tentative evidence that deficits in social networks on symptoms, recovery, and functioning is an important first and support preceded the onset of psychosis, but it was step, but also promoting awareness amongst service users difficult to disentangle direction of causation as almost and the wider public – so that people may feel more moti- all the studies included were cross-sectional and they vated to seek relevant help or to try to change their own situ- did not report whether social relationships influence ation, particularly in depression but probably in other mental outcomes of psychosis. Given that the prevalence of health problems studied too. loneliness in people with psychosis was comparable to The development of effective interventions to promote that in people with depression, it is surprising that re- social support and reduce loneliness is required to ad- search about impact of loneliness/perceived social sup- dress the current evidence gap, manifested by the ab- port on psychosis is scarce. Similarly, social relationships sence of recommendations in this important social were shown to be related to bipolar disorder and anxiety domain in current policy guidance. In the UK for ex- disorders, but there is a lack of evidence to discern cause ample, the National Health Service (NHS) Five Year For- and effect [69, 70]. Therefore more systematic explor- ward View [71] refers to a series of plans to improve the ation is needed about how loneliness and perceived so- quality of mental health services and reduce ‘burden’ on cial support affect conditions such as psychosis, bipolar the NHS. Access to psychological therapies, waiting disorder and anxiety disorders. standards and better physical healthcare are highlighted Additionally, more longitudinal research with long-term but there is no specific mention of managing the signifi- follow-up (and repeated measures) is essential to untangle cant problems of loneliness or limited social relation- the direction of effect in the relationship between loneli- ships. International evidence that poor perceived ness/perceived social support and poor outcomes. Among support from social relationships leads to increased ser- the 34 eligible studies only five articles involve a vice use and poorer outcomes across a range of diagnos- long-term follow-up period (over 2 years). Thus there is a tic groups should inform future policy in this area. Also need to establish the longer term associations of loneliness in the UK, the latest National Institute for Clinical Ex- and perceived social support. As well its effects on longer cellence (NICE) guidance on illnesses such as depression term mental health outcomes, loneliness may contribute and schizophrenia, does not recommend social interven- to the adverse physical health outcomes and increased tions apart from employment support [72, 73]. mortality of people with severe mental health problems. Clinicians may doubt whether loneliness and limited We also found that the relationship between perceived support from interpersonal relationships are appropriate social support and depression was studied far more often or feasible as targets for intervention. However, potential and is thus far more clearly established than the rela- interventions are becoming available in a variety of sec- tionship between loneliness and depression. Only two tors. Around the world, approaches are being developed studies retrieved for our review included loneliness as an to try to reduce loneliness among older people in the gen- independent variable for outcomes of mental disorders. eral population, with potential to be adapted to other They found that loneliness at baseline predicted depres- groups in the population at risk of adverse effects from sion and anxiety severity and remission from depression poor social support. In the UK, a variety of approaches to [25, 66]. However, the few longitudinal studies of loneli- social relationships and social participation are being de- ness do not allow definitive conclusions. Therefore more veloped primarily in the charitable sector and in primary longitudinal research is needed in clinical samples to try care [74]. Social prescribing projects have proliferated in to achieve a clear understanding of the impact of loneli- the UK in recent years [75]. Social prescribing is not pre- ness on the course of mental health problems. cisely defined, but typically refers to: navigation - the process of linking support for people to access community activities helpful to wellbeing and participation; and/or Clinical and policy implications funding and providing these activities in a community or There are a number of clinical and policy implications from group setting [76]. As yet however, social prescribing the finding that poor perceived social support has a signifi- models are numerous and poorly defined [75], and there cant impact on outcomes in depression. Firstly, it highlights is a lack of robust evidence regarding their effectiveness the need to pay sufficient attention to the social relationships [76]. Psychological approaches, such as Cognitive Behav- and social support needs of people with mental health prob- ioural Therapy and Mindfulness, have also been used to lems. Social activities, or thinking about relationships, can be help people change their thinking about social relation- overlooked in clinical consultations – in favour of medica- ships: some promising results have been reported, espe- tions or psychological therapies, and there have been recent cially with older adult populations [77]. Thus there are calls to raise the profile of social factors in mental health care approaches available with potential to be adapted and and mental health research [16]. Raising practitioners’ aware- tested for people with mental health problems, to try to al- ness of the beneficial effects of good perceived social support leviate the adverse effects identified in this paper. There is Wang et al. BMC Psychiatry (2018) 18:156 Page 14 of 16 also a need to consider public understanding of the im- Acknowledgments We are grateful for the help of UCL Library staff for consultation and portance of nurturing social relationships, as the high guidance in the search strategy. We would like to thank the authors of prevalence of loneliness is not only an individual but ne- screened papers who responded to our emails for their support. cessarily also a community and societal level problem. Authors’ contributions Thus people with mental health problems, like other SJ, JW and BLE conceived the review. SJ and BLE commented on search groups in the population who are vulnerable to the effects strategy and review protocol. JW developed the search strategy and review of loneliness, are likely to benefit from an approach to protocol, did the systematic search, and wrote the first draft and co-ordinated further drafts. JW and FM independently screened and selected papers for loneliness that also takes account of community resources inclusion, extracted data, and assessed the methodological quality of each and how they might be enhanced [78]. study. RM helped screen reference lists of included studies and extract data from relevant studies. SJ resolved queries about inclusion/exclusion and disagreements between JW and FM during the review process. SJ, BLE, FM, and RM contributed comments and suggestions to the drafts. All authors read and Conclusions approved the final manuscript. This systematic review has identified prospective studies in the area of loneliness/perceived social support and outcomes Ethics approval and consent to participate Not applicable. of mental health problems. We found substantial evidence that in depression, poorer perceived social support is associ- Competing interests ated with poorer outcomes in terms of symptoms, recovery The authors declare that they have no competing interests. and functioning. There is some preliminary evidence of a similar relationship in bipolar and anxiety disorders, and of a Publisher’sNote relationship between greater perceived social support and Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. better quality of life and functioning in schizophrenia. 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Associations between loneliness and perceived social support and outcomes of mental health problems: a systematic review

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Abstract

Background: The adverse effects of loneliness and of poor perceived social support on physical health and mortality are established, but no systematic synthesis is available of their relationship with the outcomes of mental health problems over time. In this systematic review, we aim to examine the evidence on whether loneliness and closely related concepts predict poor outcomes among adults with mental health problems. Methods: We searched six databases and reference lists for longitudinal quantitative studies that examined the relationship between baseline measures of loneliness and poor perceived social support and outcomes at follow up. Thirty-four eligible papers were retrieved. Due to heterogeneity among included studies in clinical populations, predictor measures and outcomes, a narrative synthesis was conducted. Results: We found substantial evidence from prospective studies that people with depression who perceive their social support as poorer have worse outcomes in terms of symptoms, recovery and social functioning. Loneliness has been investigated much less than perceived social support, but there is some evidence that greater loneliness predicts poorer depression outcome. There is also some preliminary evidence of associations between perceived social support and outcomes in schizophrenia, bipolar disorder and anxiety disorders. Conclusions: Loneliness and quality of social support in depression are potential targets for development and testing of interventions, while for other conditions further evidence is needed regarding relationships with outcomes. Keywords: Loneliness, Perceived social support, Outcomes, Mental health problems, Systematic review Background [5, 6]. They are also predictive of development of coron- There is increasing interest in the effects of social rela- ary heart disease and stroke [7], increases in systolic tions on health, and in the service delivery and policy blood pressure [8, 9], and chronic pain [10, 11] in longi- implications of such effects [1]. Loneliness has been a tudinal studies. The effect of loneliness on physical particularly prominent focus in recent research on phys- health may be via biological, psychological and/or behav- ical health [2–4]. For instance, two meta-analytic reviews ioural mechanisms, including physiological functioning, have reported that loneliness and poor social support neuroendocrine effects, gene effects, immune function- are associated with higher mortality rates, and that the ing, perception of stressful events, health behaviours and effect is comparable with some well-established risk sleep quality [2, 12, 13]. In contrast, while loneliness and factors such as obesity, physical inactivity, and smoking lack of social support are well-documented problems among mental health service users [14], they have not been prominent in research, mental health service delivery and * Correspondence: s.johnson@ucl.ac.uk policy. Until recently, there has tended to be less focus on Division of Psychiatry – University College London, 6th Floor, Maple House, the social determinants of mental health than on genetics 149 Tottenham Court Road, London W1T 7NF, England Camden and Islington NHS Foundation Trust, St Pancras Hospital, 4 St and neurobiology, but recent integrated aetiological models, Pancras Way, London NW1 0PE, England © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Wang et al. BMC Psychiatry (2018) 18:156 Page 2 of 16 such as the integrated sociodevelopmental-cognitive model, inform the development of preventive and therapeutic bring social factors into the neuroscientific mainstream, interventions for which there is not as yet an evidence with increasing evidence that such factors need to be base. An important question in evaluating the available included to achieve models of good explanatory value [15– evidence is how far loneliness is conceptually and empir- 17]. An increasing focus on loneliness has also been driven ically distinct from other concepts and measures related by recognition of its high prevalence, and of its wide ran- to social relationships. Loneliness has been shown to be ging impacts on physical health and mental well-being [17]. only moderately correlated with more objectively mea- Despite this increasing recognition of its importance, to sured concepts such as social isolation, social network date no systematic synthesis of the evidence on the rela- size and objective social support received from others tionship between loneliness and the outcomes of mental [30, 31]. However, subjectively rated concepts related to health problems has been published. social relationships are less easy to distinguish clearly Loneliness has been defined as a negative emotional from loneliness [32]. For example, perceived social sup- state that occurs when there is “a discrepancy between… port refers to people’s beliefs about how much support is the desired and achieved patterns of social interaction” potentially available from their relationships and social [18]. Loneliness is sometimes seen as an essentially uni- contacts and about the quality of this support [33, 34]. dimensional concept, sometimes as comprising two di- This is distinct from received social support, a rating of mensions. Weiss [19] proposed a multidimensional how often someone reports receiving particular support- concept of loneliness, categorising loneliness into social ive behaviours [33, 34]. Measures of perceived social and emotional dimensions. Social loneliness derived support assess the quality or adequacy of social support from “the absence of socially integrative relationships”, from a subjective perspective. For instance, the two while emotional loneliness stemmed from the absence of widely used measures, the Multi-dimensional Scale of “a close emotional attachment” [19]. Social loneliness Perceived Social Support (MSPSS) [35] and the Subject- occurs when a person does not have a wider social net- ive Support Subscale of Duke Social Support Index work as desired, which can lead to the feelings of bore- (DSSI) [36], consist of items such as “How often do you dom, exclusion and marginality [19, 20]. In contrast, feel lonely?”, “Can you talk about your deepest prob- emotional loneliness occurs when someone is missing an lems?”, “I have friends with whom I can share joys and intimate relationship, which can result in distress and ap- sorrows”, which have a high degree of overlap with lone- prehension [19, 20]. Psychometrically robust self-report liness measures. Likewise, measures of confiding rela- measures of loneliness have been developed and used ex- tionships assess the extent to which people feel close to tensively in research on physical health and on older and able to talk intimately with other people [37, 38]. people, including the University of California at Los Studies have found large negative correlations between Angeles (UCLA) Loneliness Scale [21] and the de loneliness and perceived social support [39–42]. Thus Jong-Gierveld Loneliness Scale [22]. Feelings of loneliness these concepts resemble loneliness as subjective evalua- are more prevalent among people with mental illness than tions of the quality and impact of social relationships: in the general population [23, 24]. In a study of older given this conceptual overlap, this paper includes them adults with major depression, dysthymia, or minor depres- along with loneliness. sion, 83% of the respondents reported loneliness and 38% Three previous systematic reviews have explored the reported severe loneliness [25]. By comparison, only 32% relationship between social relations and depression in of non-depressed elderly people were lonely and 4% se- general population [43, 44], or older adults [45], but in- verely lonely using the same loneliness scale [26]. In a cluded both cross-sectional and prospective studies. One comparison of people with psychosis and a general popu- further review looked at the relationship between social lation sample with similar demographic characteristics, networks and support and early psychosis in people with the prevalence of loneliness among people with psychosis first episode psychosis and in general population sam- was 79.9% compared with 35% in the general population ples, but included no prospective studies [46]. To our [27]. For people with depression, cross-sectional studies knowledge, there is no systematic review which summa- have found up to 40% of respondents feeling lonely most rises and synthesises the evidence regarding the relation- of the time [28], with a tenfold increase in the odds of be- ship between loneliness and perceived social support ing lonely compared to the general population [29]. and the course of existing mental health problems, and Given the high prevalence of loneliness among people which includes only prospective studies, from which in- with mental health problems and the evidence for its ferences about the direction of causation may be drawn. harmful effects in other populations, good quality evi- Our review will fill this gap, and will provide useful evi- dence is needed on its impact on recovery from mental dence about how far and in what context loneliness and health problems and on the health and social function- perceived social support may influence mental health re- ing of mental health service users. This has potential to covery. Thus the aim of the current paper is to Wang et al. BMC Psychiatry (2018) 18:156 Page 3 of 16 synthesise the available evidence as to whether higher outcomes. Studies in which any of the following out- levels of loneliness and poorer perceived social support comes were measured at follow-up were eligible for have an adverse effect on outcomes in adults of all ages inclusion: with existing mental health problems. 1) Relapse: recurrent episodes following recovery at Methods baseline of mental illness meeting the criteria of A systematic review was conducted of the scientific litera- DSM or ICD, or of other reliable and valid ture addressing the question of whether loneliness and low instruments such as the Center for Epidemiologic perceived social support are associated longitudinally with Studies Depression Scale (CES-D), and proxy poorer outcomes among adults of all ages with a range of measures of acute relapse such as admission to mental health problems. The review’s protocol was regis- psychiatric hospital/crisis services/acute mental tered on PROSPERO, which is an international database of health services. prospective systematic reviews with health related out- 2) Measures of functioning or of recovery: recovery of comes (registration number: CRD42015014784) [47]. function, social functioning, self-rated recovery, quality of life, and disability. Inclusion criteria 3) Symptom severity: level of symptoms, symptom Types of study: The review included longitudinal studies improvement or deterioration. in which the relationship between baseline measures of 4) Global outcome: overall outcome rating combining loneliness and poor perceived social support and out- different aspects of mental health and functioning, comes at follow up was examined using quantitative such as the Health of the Nation Outcome Scales measures. (HoNOS). Participants: Participants in the included studies were adults with mental illnesses, specifically schizophrenia Search strategy and schizoaffective disorder, psychosis in general, de- A systematic search of the following six electronic data- pression, bipolar disorder, and anxiety disorders. Clinical bases was undertaken: Medline, PsycINFO, Embase, populations were included however diagnosis was made, Web of Science, CINAHL and Cochrane Library (1891 for example clinical diagnoses, ratings according to the to April 2016). No language and publication period re- criteria of the Diagnostic and Statistical Manual of Men- strictions were applied. Search terms for loneliness and re- tal Disorders (DSM) or the International Classification lated concepts were combined with terms for mental of Diseases (ICD), or use of reliable and valid instru- disorders and outcomes. Searches were conducted using ments such as the Mini-International Neuropsychiatric both subject headings (MeSH terms) and text words within Interview (M.I.N.I.). We excluded studies with samples title and abstract. Search terms were adapted as required of children under 16 years old, people with intellectual for different databases (for full details, see Additional file 1). disabilities or organic mental disorders including demen- The search terms used in Medline are as follows: tia, or cohorts assembled on the basis of a primary phys- ical illness diagnosis. 1) Loneliness: loneliness [MeSH] OR loneliness OR Exposure variables: Included studies used quantitative lonely OR social support adj5 (subjective or measures of loneliness or of related concepts that in- personal or perceived or quality) OR confiding volve a subjective rather than objective appraisal of so- relationship* cial relationships, such as perceived social support or 2) Mental disorders: mental disorders [MeSH]. exp. confiding relationships. Concepts based on objective rat- OR mental OR psychiatr* OR schizo* OR psychosis ings of the size and functioning of social networks, such OR psychotic OR depress* OR mania* OR manic as social isolation and social network size, were ex- OR bipolar adj5 (disorder or disease or illness) OR cluded. Social capital was also excluded as it relates to anxiety disorders [MeSH]. exp. characteristics of society or communities as a whole as 3) Outcomes: prognosis [MeSH] OR outcome* OR well as individuals’ appraisal of their relationships, and is recurren* OR relapse OR admission OR conceptually distinct from loneliness [32]. We included hospitali?ation OR crisis OR admitted OR detained studies only if exposure variables assessed subjective ap- OR detention OR recovery of function [MeSH] OR praisal of overall social connectedness, rather than the “social functioning” OR “self-rated recovery” OR quality of specific relationships: therefore, measures of “quality of life” OR “symptom severity” OR support from partner and quality of a specific significant disability relationship were excluded. Outcomes: The review included a wide variety of out- Apart from outcome terms, we searched “onset” and comes, ranging from clinical outcomes to functioning related terms as searches were conducted simultaneously Wang et al. BMC Psychiatry (2018) 18:156 Page 4 of 16 for this and a companion systematic review on loneliness narrative synthesis of results as the anticipated hetero- as a risk factor for the onset of psychiatric disorders in geneity of included studies, for example in samples, pre- the general population. Reference lists of studies identi- dictor measures and outcomes, made a meta-analysis fied through the electronic search for inclusion in the re- inappropriate. The main results have been stratified by view and of review articles were manually searched for type of mental health problem investigated and tables further relevant studies. Relevant studies reported in dis- and text were used to summarise the data. sertations, conference reports or other sources other than published journals were searched using the free text Results and keyword searches from the following two sources: Literature search Zetoc (indexing and abstracting database of conference Our initial database search retrieved 13,076 records (see proceedings) and OpenGrey (system for information on Fig. 1). After excluding duplicates and screening titles grey literature in Europe). When necessary and possible, and abstracts to exclude obviously irrelevant papers, 797 we sent emails to authors to request full text or clarify full-text articles were assessed for eligibility. 734 studies some uncertainties. were excluded because: i) they were not longitudinal Selection of studies for inclusion in the review was quantitative studies; ii) they assessed a form of social re- made independently by two reviewers (J.W. & F.M.). Ti- lationships conceptually distinct from loneliness or per- tles of all identified studies were screened. The abstracts ceived social support; iii) they analysed the relationship of potentially relevant studies were read; the full text of between change scores in loneliness and outcome vari- studies still considered potentially relevant was then re- ables, rather than baseline loneliness as a predictor of trieved and read. All studies included by one assessor outcome; or iv) they investigated a sample consisting of were confirmed by the other reviewer to check adher- children under 16 years old or of people with primary ence to inclusion criteria in study selection. 800 studies diagnoses of drug and alcohol disorders, personality dis- excluded by one assessor were checked by the other re- orders, post-traumatic stress disorder (PTSD), learning viewer to establish reliability of our study selection. The disabilities or organic mental disorders, or of people re- agreement between reviewers was higher than 99%. cruited as having specific physical illnesses. Twenty-two Queries about inclusion/exclusion were resolved through further papers were retrieved by hand-searching the ref- discussion with a third reviewer (S.J.). erence lists of the papers already identified. Of the resulting 85 studies, 34 articles about outcomes of men- Data extraction, quality assessment and synthesis tal disorders among people with existing mental health A structured template was developed to extract relevant problems were included in this review. The other 51 pa- data from eligible papers. Two review authors (J.W. & pers will be reported in a companion systematic review F.M.) independently extracted data and assessed their regarding the relationship between loneliness and onset methodological quality. Extracted data and quality as- of mental health problems in the general population. sessment scores were checked by a second reviewer for The search results are reported as a Prisma diagram in 20% of papers. Disagreements between the two assessors the Fig. 1. were resolved through discussion with a third review au- thor (S.J.). The methodological quality of each study in- Eligible papers cluded in the review was assessed using a standard form The 34 eligible papers were from seven countries, in- adapted from the Mixed Methods Appraisal Tool cluding 23 from North America, 10 from Europe and (MMAT) – Version 2011 [48]. The MMAT has been de- one from Israel. These papers consisted of 23 studies signed for appraisal of the methodological quality for with samples of people with depression, two focusing on qualitative, quantitative and mixed methods studies. For schizophrenia or schizoaffective disorders, four on bipo- quantitative studies it includes criteria relevant to rando- lar disorder, and three on anxiety disorders. Two further mised controlled, non-randomised, and descriptive stud- studies included people with a mixture of mental health ies. For the purposes of our review, we used the criteria problems (Table 1). Only two studies directly assessed for the quantitative non-randomised domain (Cohort loneliness, and most of the studies used various scales to study version). As there are four criteria for this domain measure perceived social support. Nearly half of in- following two screening questions, the overall quality cluded papers studied symptom severity as an outcome, score was presented using descriptors *, **, ***, and ****, a third of the papers assessed recovery/remission, and a ranging from * (one criterion met) to **** (all criteria third of the papers included other outcomes such as met). The four criteria related to selection bias, meas- quality of life, disability pension qualification, functional urement quality, adjustment for confounders, and per- impairment or life satisfaction. The sample sizes of six centage of complete outcome data/response rate/ studies in our review exceeded 400, 22 were between follow-up rate (see Additional file 2). We conducted a 100 and 400, and six were less than 100. Six studies had Wang et al. BMC Psychiatry (2018) 18:156 Page 5 of 16 Fig. 1 Studies selection flowchart short length of follow-up (less than one year), 23 follow- significant predictor of higher depressive symptom se- ing up the cohorts for one to two years, and five for over verity at follow-ups (Table 2). Nine of these eleven pa- two years. With regard to quality assessment, five studies pers conducted multivariable analyses including were assigned a maximum score of four (****) as their adjusting for baseline depression severity. In eight of overall quality scores, 16 studies had a score of three these nine papers, the relationship between baseline (***) and 13 papers had two (**) according to the loneliness and depressive symptom outcome remained appraisal criteria of MMAT. Most studies had lower significant. For example, among the three studies with quality assessment ratings because they did not report high quality scores (****), Blazer and colleagues [49] and the percentage of complete outcome data, response rate Brugha and colleagues [50] followed cohorts of adults or follow-up rate (for full details, see Additional file 2). with depression in America and the UK respectively. They reported that poorer subjective social support at Depression baseline was predictive of poorer outcomes at follow-up, Among the 23 papers with samples of people with de- outcomes including poorer life satisfaction (beta = 0.10, pression, 13 studies assessed depression severity as an B = 0.37), worse depressive symptoms (beta = 0.10, B = outcome. Eleven of these found that poorer perceived 0.30) [49], and more severe psychiatric status (regression social support or greater loneliness at baseline was a coefficient = − 1.46) [50]. In the third study rated as high Wang et al. BMC Psychiatry (2018) 18:156 Page 6 of 16 Table 1 Summary of characteristics of included studies Condition studied Predictor variable Outcomes Sample size range (median) Length of follow-up Follow-up rate range (median) Quality score Depression (n = 23) Perceived social support (n = 22) Symptom severity (n = 13) 66–604 (239) Short (n =4) 60.6–100% (81.9%) **** (n =4) Loneliness (n =1) Recovery/remission (n =7) Medium (n = 14) *** (n = 11) Functional outcomes (n =5) Long (n =5) ** (n =8) Schizophrenia/schizoaffective Perceived social support (n = 2) Functional outcomes (n = 2) 139–148 (143.5) Medium (n = 2) 71.9–100% (86.0%) *** (n =1) disorders (n =2) ** (n =1) Bipolar disorder (n = 4) Perceived social support (n = 4) Symptom severity (n =3) 42–173 (55.5) Short (n =1) 71.1–100% (86.4%) *** (n =2) Recovery/remission (n =2) Medium (n = 3) ** (n =2) Functional outcomes (n =2) Anxiety disorders (n = 3) Perceived social support (n = 3) Symptom severity (n =1) 134–1004 (1004) Short (n =1) 80–87% (81.0%) **** (n =1) Recovery/remission (n =1) Medium (n =2) *** (n =1) Functional outcomes (n =1) ** (n =1) Mixed samples with various mental Perceived social support (n =1) Symptom severity (n =1) 352–743 (547.5) Medium (n = 2) 79.9–84.4% (82.2%) *** (n =1) health problems (n = 2) Loneliness (n =1) Functional outcomes (n =1) ** (n =1) Length of follow-up: Short = < 1 year; Medium = 1–2 years; Long = > 2 years. ** = two criteria of MMAT met. *** = three criteria of MMAT met. **** = all criteria of MMAT met Wang et al. BMC Psychiatry (2018) 18:156 Page 7 of 16 Table 2 Summary of findings on depression Reference Predictor Outcome variable Results (++ < 0·05 adjusted; + < 0·05 unadjusted; − variable non-significant) Hybels et al. (2016) [79] Perceived social Trajectory class ++ Patients in the persistent moderate depression class had support (quick recovery, lower levels of baseline subjective social support compared slow recovery, with patients in the quick recovery class (OR (95%CI) = 0.91 persistent moderate, (0.83, 0.98)). Patients in the persistent high depression class and persistent high) had lower levels of baseline subjective social support compared with those in the quick recovery class (OR (95%CI) = 0.83 (0.75, 0.92)) Holvast et al. (2015) [25] Loneliness Symptom severity; ++ In the fully adjusted model, a 1-point higher baseline Remission ++ loneliness score predicted a 0·61-point higher depressive symptom severity score at follow-up (Beta = 0.61, 95% CI 0.12–1.11, p = 0.02). Logistic regression analysis showed that while adjusting for social network size and potential confounders, the very severely lonely respondents were less likely to achieve remission from their depressive disorder compared with the non-lonely respondents (OR = 0.25, 95% CI 0.08–0.80, p = 0.02). Holma et al. (2012) [54] Perceived social Disability pensions + Lower perceived social support at baseline predicted greater support likelihood of being granted a disability pension over 5 year follow-up on univariate analysis (p = 0.031), but not significant in multivariate analyses where the outcome was the interval time to the date the pension was granted Backs-Dermott et al. (2010) [80] Perceived social Relapse versus stable ++ Lower perceived social support from a significant other support remitted (standardized discriminant function coefficient 0.48) and lower perceived social support from friends (standardized coefficient 0.35) at baseline predicted greater likelihood of depressive relapse at one-year follow-up. The Discriminant Function Analysis was significant, Wilk’s Lambda = 0.69, x (5) = 16.35, p = 0.006 Bosworth et al. (2008) [81] Perceived social Depression severity ++ Poorer subjective social support was a significant predictor support of more severe depression at 12 months. Standardized beta = − 0.13, p = 0.05 Rytsala et al. (2007) [55] Perceived social Work disability + Lower perceived social support at 6 month was a significant support allowances predictor of greater likelihood of being granted disability allowances at 18 months (F = 6.3, p = 0.013), but not significant in multivariate analysis Rytsala et al. (2006) [56] Perceived social Functional disability; ++ Lower perceived social support at baseline was a significant support Social and work ++ predictor of more severe functional disability at 6 months adjustment; − (B = 0.232, β = 0.210, p = 0.002, 95% CI 0.084 to 0.379), and Days spent ill in poorer social and work adjustment at 6 months (B = − 0.008, bed or not β = − 0.222, p = 0.001, 95% CI -0.013 to − 0.003). Lower perceived social support at 6 months was one of the most significant factors predicting more severe functional disability at 18 months (B = 0.240, β = 0.215, p = 0.002, 95% CI 0.088 to 0.393), and poorer social and work adjustment at 18 months (B = − 0.011, β = − 0.303, p‹0.001, 95% CI -0.015 to − 0.006). But perceived social support did not predict any days spent ill in bed or not Leskela et al. (2006) [51] Perceived social Severity of depression + Lower perceived social support at 6 months predicted support more severe depression at 18 months in original zero-order correlation (r = − 0.392, p < 0.001) and within-group standardised correlation (r = − 0.230, p = 0.001) among all patients, but not significant in multivariate analysis. In full remission group at 6 months (n = 67), lower perceived social support at 6 months predicted higher level of depressive symptoms at 18 months in multivariate analysis (r = − 0.321, p = 0.012) Steffens et al. (2005) [82] Perceived social Severity of depression ++ Lower subjective social support at baseline predicted more support severe depression over time (estimate − 0.5641, p = 0.0002) Ezquiaga et al. (2004) [83] Perceived social Episode remission – Higher perceived social support at baseline did not predict support remission at 12 months in univariate analysis (p = 0.33), and it was not included in multivariate analysis Wang et al. BMC Psychiatry (2018) 18:156 Page 8 of 16 Table 2 Summary of findings on depression (Continued) Reference Predictor Outcome variable Results (++ < 0·05 adjusted; + < 0·05 unadjusted; − variable non-significant) Reference Predictor Outcome variable Results (++ < 0·05 adjusted; + < 0·05 unadjusted; − variable non-significant) Gasto et al. (2003) [84] Perceived social Severity of residual ++ Lower subjective social support at baseline predicted support symptoms higher intensity of residual symptoms at 9 months in remitters (standardized β = 0.41, p < 0.001) Bosworth et al. (2002) [53] Perceived social Time-to-remission ++ Lower subjective social support at baseline (Hazard support Ratio = 0.47, 95% CI: 0.31–0.71, p = 0.003) was a significant predictor of longer time to remission Bosworth et al. (2002) [52] Perceived social Remission ++ Lower baseline levels of subjective social support support (OR = 1.21, 95% CI: 1.09–1.35, p < 0.001) predicted poorer recovery one year later Triesch (2002) [85] Perceived social Severity of depressive − Lower perceived social support at baseline did not support symptoms; − predict more severe depression (β = − 0.17) or poorer Quality of life quality of life (β = − 0.12) at 3 months Hays et al. (2001) [57] Perceived social Activities of daily living ++ There was modest support for hypothesis that baseline support subjective social support predicted functional declines at 1 year. There was partial support for hypothesis that the buffering effects of social support against functional decline would be strongest among the most severely depressed patients Oxman and Hull (2001) [86] Perceived social Depression severity ++ Greater perceived social support predicted subsequent support decreases in depression among participants randomly assigned to placebo group (6-week depression − 0.18, p < 0.05; 11-week depression − 0.22, p < 0.05), but not significant among paroxetine group or Problem-Solving Treatment for Primary Care group Brummett et al. (2000) [87] Perceived social Depressive symptoms – Higher levels of received support at baseline significantly support predicted decreases in depressive symptoms at both 6 months and 1 year, whereas subjective support did not significantly predict changes in depressive symptoms at either point in time Sherbourne et al. (1995) [88] Perceived social Number of depressive ++ Decreased number of depressive symptoms between support symptoms baseline and 2-year follow-up was predicted by social support at baseline (standardised regression coefficients = 0.12, zero-order Pearson product-moment correlations = 0.16, p < 0.05). Among the subset of patients who had current depressive disorder at baseline, perceived social support was not significantly related to remission. Among patients without current depressive disorder at baseline (subthreshold depression), patients with higher level of perceived social support were less likely to experience a new depressive episode during 2-year period: odds ratio = 0.96 (CI:0.95, 0.98) Blazer et al. (1992) [49] Perceived social Decreased life satisfaction ++ Impaired subjective support at baseline was predictive support symptoms; of poorer outcome at 12-month follow-up in both models: Endogenous symptoms decreased life satisfaction symptoms (b = 0.10, B = 0.37, p ≤ 0.001), endogenous symptoms (b = 0.10, B = 0.30, p≤ 0.01) Blazer et al. (1991) [89] Perceived social Depressive symptoms + Intercorrelation between social support at baseline and support depression score at 6 months: − 0.41, p < 0.001. Intercorrelation between social support at baseline and depression score at 12 months: − 0.34, p < 0.001 Brugha et al. (1990) [50] Perceived social Symptom severity ++ After controlling for the two significant clinical predictors, support a significant main effect was found in total sample for lower satisfaction with support at baseline on more severe psychiatric status at 4 months (regression coefficient = − 1.46, p < 0.05) Wang et al. BMC Psychiatry (2018) 18:156 Page 9 of 16 Table 2 Summary of findings on depression (Continued) Reference Predictor Outcome variable Results (++ < 0·05 adjusted; + < 0·05 unadjusted; − variable non-significant) George et al. (1989) [90] Perceived social Depressive symptoms ++ Impaired subjective social support at baseline is a support significant predictor of higher numbers of CES-D symptoms at follow-up (b = 8.88, B = 0.20, p ≤ 0.05) Krantz and Moos (1988) [91] Perceived social Remitted, partially + Lower quality of relationships at baseline predicted support remitted, and poorer remission status after 1 year (χ = 10.21, p < 0.01) nonremitted quality, Leskela and colleagues [51] assessed adults with later (OR = 1.21, 95% CI 1.09–1.35) [52], and of lon- major depressive disorder and found that lower per- ger time-to-remission in a study of initially de- ceived social support six months after initial assessment pressed elderly individuals (Hazard Ratio = 0.47, 95% predicted more severe depression at 18 months among CI 0.31–0.71) [53]. However, none of the seven stud- all participants, although this relationship only remained ies had high quality scores (****), with five receiving significant in multivariable analysis for the group who medium (***), and two low scores (**). had remitted following initial assessment (r = − 0.321). With regard to functional outcomes (five articles), The only study using loneliness as a predictor of depres- three studies have found that lower perceived social sup- sion outcomes was conducted by Holvast and colleagues port at baseline was a significant predictor of greater [25] among Dutch older adults. They found that a likelihood of being granted disability pensions during 1-point higher loneliness score was predictive of a the follow-up period (no effect size reported) [54, 55] 0.61-point higher depressive symptom severity score at and of more severe functional disability (beta 0.210 to follow-up (Beta = 0.61, 95% CI 0.12–1.11). For studies 0.215, 95% CI 0.084–0.393) [56]. There is also evidence which reported beta as the effect size, beta ranged from that greater perceived social support predicted better so- 0.10 to 0.61. Among the 13 studies, three articles had cial and work adjustment (beta − 0.222 to − 0.303, 95% high quality (****), four had medium quality (***), and CI -0.013 to − 0.006) [56], and buffered functional de- the other six received low quality ratings (**). However, clines in performance on activities of daily living (no ef- no obvious relationship was found between study quality fect size reported) [57]. However, after adjustment for and whether results were significant. potential confounders only two [56, 57] of the five stud- Six out of seven articles which used recovery/re- ies had significant results. mission of depression as their outcomes reported lower perceived social support or higher loneliness at baseline as a significant predictor of lower rates Schizophrenia/schizoaffective disorders of recovery/remission at follow-up. Three of the Two studies assessed patients with schizophrenia or seven studies adjusted for baseline depression sever- schizoaffective disorders to identify psychosocial predic- ity, and all of them reported significant results. For tors of health-related quality of life and functional out- example, in the study of Holvast et al. [25], the comes (Table 3). Ritsner and colleagues [58] followed a lonely respondents at baseline were reported to be sample of inpatients with schizophrenia or schizoaffec- less likely to achieve remission from their depressive tive disorders for 16 months and found that greater sup- disorder at follow-up compared with the non-lonely port from friends at baseline predicted better satisfaction respondents (OR = 0.25, 95% CI 0.08–0.80). Similarly, with life quality after 16 months (accounted for 2.9% of poorer perceived social support at baseline was a quality of life index scores at follow up examination). In significant predictor of poorer recovery one year an American study, greater perceived social support was Table 3 Summary of findings on schizophrenia and schizoaffective disorders Reference Predictor variable Outcome variable Results (++ < 0·05 adjusted; + < 0·05 unadjusted; − non-significant) Ritsner et al. (2006) [58] Perceived social support Quality of life ++ Higher friend support at baseline predicted better satisfaction with life quality after 16 months (accounted for 2.9% of quality of life index scores at follow up examination) Brekke et al. (2005) [59] Perceived social support Global functional outcome − Higher social support did not significantly predict (work, social functioning, and better global functional outcome at 12 months independent living); (p < 0.10). But social support became a much Social functioning domain ++ stronger and statistically significant predictor of social functioning domain Wang et al. BMC Psychiatry (2018) 18:156 Page 10 of 16 a strong predictor of better scores on a social function- recurrence, the other three had adjustment for baseline ing domain (no effect size reported), although it did not score on the outcome measure. predict the global functioning score (a composite of vo- cational and social functioning, and independent living) Anxiety disorders [59].However, neither of these studies adjusted for the The three studies of patients with anxiety disorders all re- outcome variable baseline scores. ported significant associations between perceived social support at baseline and outcomes at follow-up (Table 5). Bipolar disorder Two studies included people with diagnoses of generalised We found four papers that studied adults with a diagno- anxiety disorder, panic disorder, social anxiety disorder or sis of bipolar disorder (Table 4). The evidence regarding post-traumatic stress disorder. One study found that lower depressive symptoms was consistent and showed that perceived social support was predictive of more severe lower perceived social support predicted greater depres- anxiety (beta = − 0.15, CI [− 0.30, − 0.06], Ratios 8.85%) sion over time (beta − 0.14 to − 0.25, regression coeffi- and depressive symptoms (beta = − 0.16, CI [− 0.28, − cient − 1.33) [60–62]. Lower perceived support was also 0.08], Ratios 10.51%) at subsequent time points [33], and found to be a significant predictor of greater impairment the other one found that greater perceived social support in functioning (beta − 0.14 to − 0.67) [60, 61], and longer predicted a higher rate of remission at 6-month follow-up time to recovery (no effect size reported) [62]. Among (OR = 1.38, 95% CI Wald 1.09–1.75) [64]. In a study of remitted patients with prior diagnosis of bipolar I dis- older adults with generalised anxiety disorder, Shrestha et order, greater perceived social support reduced risk of al. [65] found that individuals with greater perceived social recurrence of any type (depressive or manic) at one year support at baseline reported greater average quality of life (OR = 0.92, 95% CI 0.85–0.99) [63]. With regard to se- over time (beta = 0.41), albeit without adjustment for the verity of manic symptoms, however, the results were not outcome variable baseline score. so consistent. In one study lower perceived support sig- nificantly predicted more severe manic symptoms on Mixed samples with various mental health problems follow-up assessment (beta = − 0.32) [61], but in other Two studies examined mixed samples of people with a two studies it was not linked with subsequent manic variety of diagnoses (Table 6). Beljouw et al. [66]ana- symptomatology [60, 62]. Apart from the study of lysed data from primary care patients with current anxiety Table 4 Summary of findings on bipolar disorder Reference Predictor variable Outcome variable Results (++ < 0·05 adjusted; + < 0·05 unadjusted; − non-significant) Koenders et al. (2015) [60] Perceived social Depressive symptomatology; ++ Lower perceived support predicted more depression support Depression related functional ++ related functional impairment during the subsequent impairment; 3 months (β (SE) = − 0.14 (0.03), p < 0.001), and with Manic symptomatology; more depressive symptomatology at the subsequent Manic related functional time point (β (SE) = − 0.14 (0.04), p = 0.002). No significant impairment associations between perceived social support and manic symptoms and impairment were observed Cohen et al. (2004) [63] Perceived social Recurrence ++ After controlling for clinical variables, lower social support support of any kind significantly predicted recurrence of any type at one year (β (SE) = − 0.09 (0.04), p = 0.03, OR = 0.92, 95% CI 0.85–0.99) Daniels (2000) [61] Perceived social Depressive symptomatology; ++ Lower perceived support was a significant predictor of support Manic symptomatology; ++ more severe depressive symptomatology after controlling 2 2 Functional impairment ++ for initial levels of depression (R = 0.67, F = 34.15, ΔR = 0.05, ΔF = 5.24, beta = − 0.25). Lower perceived support significantly predicted more severe manic symptomatology over three 2 2 months (R = 0.18, F = 3.74, ΔR = 0.10, ΔF = 4.18, beta = − 0.32). Lower perceived social support significantly predicted impairment in functioning in the participants who completed their life charts for 90 consecutive days, after controlling for initial levels of 2 2 functional impairment (R = 0.44, F = 5.48, ΔR = 0.41, ΔF = 10.22, beta = − 0.67). Johnson et al. (1999) [62] Perceived social Time to recovery; ++ Lower social support was a significant predictor of longer time support Severity of depressive ++ to recovery in Cox regression survival analyses (χ2 (1, N = 52) symptoms; − change = 5.89, one-tailed p < 0.01). In hierarchical multiple Severity of manic symptoms regression analyses, low social support predicted higher depression over time (regression coefficient = − 1.33, p < 0.01, R change = 0.07, F change = 11.70). Social support did not have significant impact on mania score at 6-month follow-up Wang et al. BMC Psychiatry (2018) 18:156 Page 11 of 16 Table 5 Summary of findings on anxiety disorders Reference Predictor variable Outcome variable Results (++ < 0·05 adjusted; + < 0·05 unadjusted; − non-significant) Jakubovski and Bloch (2016) [64] Perceived social Remission; ++ Generalised anxiety disorder: Greater amount of social support Response (a reduction ++ support predicted a higher rate of remission (OR = 1.38, of at least 40% symptoms 95% CI Wald 1.09–1.75, p = 0.0067) and a greater rate of at 6 months) response (OR = 1.33, 95% CI Wald 1.10–1.62, p = 0.0040) at 6-month follow-up. Social anxiety disorder: Greater amount of social support predicted a higher rate of remission (OR = 1.716, 95% CI Wald 1.028–2.867, p = 0.0391) at 6-month follow-up, but social support did not predict response. Social support did not predict remission or response for panic disorder or post-traumatic stress disorder Shrestha et al. (2015) [65] Perceived social Quality of life ++ Main effect of social support was significant such that support those with higher baseline social support reported higher average quality of life over time (b (SE) = 0.41 (0.08), p < 0.001) Dour et al. (2014) [33] Perceived social Anxiety symptoms; ++ Direct effects: Relations between perceived social support Depressive symptoms ++ support and depression were bidirectional at all follow-ups, whereas they were unidirectional between perceived social support and anxiety at 6- and 12-month follow-ups. Indirect effects: Intervention led to changes in 6- and/or 12-month perceived social support, that in turn led to subsequent changes in 18-month depression (b = − 0.16, CI [− 0.28, − 0.08], Ratios 10.51%) and anxiety (b = − 0.15, CI [− 0.30, − 0.06], Ratios 8.85%) or depressive disorders, and found that greater loneliness Discussion at baseline was predictive of more severe depressive (beta Main findings = 0.89) or anxiety symptoms (beta = 0.40) at 1-year We found 34 studies that reported quantitatively on the follow-up. However, after adjustment for baseline severity longitudinal relationship between perceived social sup- of depression or anxiety, only the relationship with de- port/loneliness at baseline and various outcomes of pression severity remained significant (beta = 0.39). Fleury mental illness at follow-up. Although substantial hetero- and colleagues [67] conducted a study among individuals geneity exists in the identified articles, some generalisa- with severe mental health problems including schizophre- tions can be made. There is substantial evidence that nia and other psychotic disorders and severe mood disor- less perceived social support at baseline tends to predict ders. They reported that greater perceived social support greater symptom severity, poorer recovery/remission was significantly predictive of higher subjective quality of and worse functional outcomes at follow-up among life at 18 months (beta 0.136 to 0.196, 95% CI 0.255 to people with depression, and preliminary evidence of a 3.410). However, adjustments for baseline measures in- similar relationship for people with bipolar disorder, or cluded functional ability in the community and diagnosis, anxiety disorders. There is also some evidence that but not baseline quality of life. greater loneliness is associated with more severe Table 6 Summary of findings on mixed samples with various mental health problems Reference Predictor variable Outcome variable Results (++ < 0·05 adjusted; + < 0·05 unadjusted; − non-significant) Fleury et al. (2013) [67] Perceived social Subjective quality ++ Social support variables at baseline accounted for 7.9% of support of life quality of life at 18-month follow-up. Among social support dimensions, higher perception of availability of social integration (β = 0.196, t = 3.472, p = 0.001, 95% CI [0.942, 3.410]) and reassurance of worth supports (β = 0.136, t = 2.397, p = 0.017, 95% CI [0.255, 2.597]) at baseline predicted better quality of life at 18-month follow-up Van Beljouw et al. (2010) [66] Loneliness Severity of ++ A higher symptom severity in depression at 1-year follow-up was depression; + predicted by more loneliness at baseline in both multilevel univariate Severity of anxiety linear regression analyses (β = 0.89, SE = 0.17, p < 0.001) and multilevel multivariate linear regression analyses (β = 0.39, SE = 0.16, p < 0.05). Positive associations were found between more symptom severity in anxiety at 1-year follow-up and loneliness at baseline by multilevel univariate linear regression analyses (β = 0.40, SE = 0.12, p < 0.01) (but not significant in multivariate analyses) Wang et al. BMC Psychiatry (2018) 18:156 Page 12 of 16 depression and anxiety symptoms and poorer remission although they all measure individuals’ subjective ap- from depression. An important consideration in inter- praisal of adequacy or impact of their relationships ra- preting findings is that depression is very likely to make ther than objective or structural social support. Both people more likely to appraise their social support as in- loneliness studies used a published measure of loneliness adequate and to feel emotionally lonely. However, a per- with well-established psychometric properties, but this sistent effect on outcomes is found in many studies with review shows that knowledge about the relationship be- adjustment for baseline depression severity. With regard tween loneliness and outcomes of mental health prob- to schizophrenia/schizoaffective disorders, only func- lems is still very limited. Finally, the studies in our tional outcomes have been studied and the small review had sample sizes ranging from 42 to 1004, and amount of available evidence suggests that greater per- diverse follow-up periods from a few months to ten ceived social support is predictive of better subjective years. The sample size of most studies is under 400 with quality of life and social functioning. This review, to our less than 100 participants in six articles. However, the knowledge, is the first to systematically examine longitu- consistency of positive findings from included studies, ir- dinal studies regarding the relationship between loneli- respective of their sample size, provides some confidence ness and closely related concepts and outcomes for that studies were not underpowered. adults of all ages and all types of mental illness. Other limitations of this review relate to the search strategy. Although our literature search was conducted Strengths and limitations of the included studies and of in six databases and a variety of search terms were ap- this review plied, the search might not be exhaustive. Some relevant Generally, the quality of included studies is acceptable studies may have been missed if they did not use “sub- and most studies were assigned at least *** as their over- jective or personal or perceived or quality” five or fewer all quality scores in accordance with the methodological words apart from “social support”. Some very old papers quality criteria of MMAT. However, some methodo- might not be indexed in electronic databases, and thus logical issues in the published literature may limit what cannot be searched. Eligible studies are only from seven can be inferred from the studies. Many studies did not countries and most of them were conducted in North have comprehensive information about percentage of America. Very few papers in other languages were re- complete outcome data, baseline response rate, or trieved and none of them could be included in our re- follow-up rate, resulting in lower quality assessment rat- view, although we did search for them and read their ings. We did assess whether studies adjusted for baseline abstracts. It is also worth noting that the extent of any measurements on the outcomes. Some did not, increas- reporting bias is uncertain as studies which did not find ing uncertainty about the direction of causation (al- a positive result might not be published. Another limita- though if the baseline outcome measure which included tion refers to the scope of our review. We restricted the random errors was introduced as a covariate, regression search to the most common mental disorders, including to the mean might lead to biased results according to schizophrenia and schizoaffective disorder, psychosis in Lord’s paradox [68]). A large majority of the 23 studies general, depression, bipolar disorder, and anxiety disor- that did adjust for baseline outcome measures still found ders. The associations between loneliness and perceived loneliness/perceived social support to be predictive of social support and other mental health problems need outcomes. This suggests that there is a real effect of further investigation. Additionally, we focused on one loneliness/lack of social support on outcomes. However, direction of causation only: the effect of baseline loneli- it is likely that the relationship can be a circular one, ness and poor perceived social support on mental health with loneliness/lack of social support resulting in more outcomes at follow up. Psychiatric symptoms probably severe symptoms, and more severe symptoms exacerbat- also influence loneliness and perceived social support, ing loneliness/lack of social support. but this was not the research question on which we fo- The consistency of findings across a variety of settings, cused in this review. measures of the exposure, and population groups in- creases confidence in the generalisability of the review’s Research implications findings. The retrieved articles encompassed varying Most studies included in our review focused on depres- populations including older and younger groups, and sion, with other types of mental health problems repre- people recruited in primary care, inpatient and out- sented by fewer than five studies each. Nevertheless, patient settings, and were carried out around the world. some significant relationships have been found between Most studies of perceived social support used loneliness and/or perceived social support and outcomes well-developed scales where psychometric properties of those mental disorders. Gayer-Anderson and Morgan have been established. The measures used varied regard- [46] systematically examined evidence on social net- ing the dimensions and types of social support assessed, works and social support in early psychosis. They found Wang et al. BMC Psychiatry (2018) 18:156 Page 13 of 16 some tentative evidence that deficits in social networks on symptoms, recovery, and functioning is an important first and support preceded the onset of psychosis, but it was step, but also promoting awareness amongst service users difficult to disentangle direction of causation as almost and the wider public – so that people may feel more moti- all the studies included were cross-sectional and they vated to seek relevant help or to try to change their own situ- did not report whether social relationships influence ation, particularly in depression but probably in other mental outcomes of psychosis. Given that the prevalence of health problems studied too. loneliness in people with psychosis was comparable to The development of effective interventions to promote that in people with depression, it is surprising that re- social support and reduce loneliness is required to ad- search about impact of loneliness/perceived social sup- dress the current evidence gap, manifested by the ab- port on psychosis is scarce. Similarly, social relationships sence of recommendations in this important social were shown to be related to bipolar disorder and anxiety domain in current policy guidance. In the UK for ex- disorders, but there is a lack of evidence to discern cause ample, the National Health Service (NHS) Five Year For- and effect [69, 70]. Therefore more systematic explor- ward View [71] refers to a series of plans to improve the ation is needed about how loneliness and perceived so- quality of mental health services and reduce ‘burden’ on cial support affect conditions such as psychosis, bipolar the NHS. Access to psychological therapies, waiting disorder and anxiety disorders. standards and better physical healthcare are highlighted Additionally, more longitudinal research with long-term but there is no specific mention of managing the signifi- follow-up (and repeated measures) is essential to untangle cant problems of loneliness or limited social relation- the direction of effect in the relationship between loneli- ships. International evidence that poor perceived ness/perceived social support and poor outcomes. Among support from social relationships leads to increased ser- the 34 eligible studies only five articles involve a vice use and poorer outcomes across a range of diagnos- long-term follow-up period (over 2 years). Thus there is a tic groups should inform future policy in this area. Also need to establish the longer term associations of loneliness in the UK, the latest National Institute for Clinical Ex- and perceived social support. As well its effects on longer cellence (NICE) guidance on illnesses such as depression term mental health outcomes, loneliness may contribute and schizophrenia, does not recommend social interven- to the adverse physical health outcomes and increased tions apart from employment support [72, 73]. mortality of people with severe mental health problems. Clinicians may doubt whether loneliness and limited We also found that the relationship between perceived support from interpersonal relationships are appropriate social support and depression was studied far more often or feasible as targets for intervention. However, potential and is thus far more clearly established than the rela- interventions are becoming available in a variety of sec- tionship between loneliness and depression. Only two tors. Around the world, approaches are being developed studies retrieved for our review included loneliness as an to try to reduce loneliness among older people in the gen- independent variable for outcomes of mental disorders. eral population, with potential to be adapted to other They found that loneliness at baseline predicted depres- groups in the population at risk of adverse effects from sion and anxiety severity and remission from depression poor social support. In the UK, a variety of approaches to [25, 66]. However, the few longitudinal studies of loneli- social relationships and social participation are being de- ness do not allow definitive conclusions. Therefore more veloped primarily in the charitable sector and in primary longitudinal research is needed in clinical samples to try care [74]. Social prescribing projects have proliferated in to achieve a clear understanding of the impact of loneli- the UK in recent years [75]. Social prescribing is not pre- ness on the course of mental health problems. cisely defined, but typically refers to: navigation - the process of linking support for people to access community activities helpful to wellbeing and participation; and/or Clinical and policy implications funding and providing these activities in a community or There are a number of clinical and policy implications from group setting [76]. As yet however, social prescribing the finding that poor perceived social support has a signifi- models are numerous and poorly defined [75], and there cant impact on outcomes in depression. Firstly, it highlights is a lack of robust evidence regarding their effectiveness the need to pay sufficient attention to the social relationships [76]. Psychological approaches, such as Cognitive Behav- and social support needs of people with mental health prob- ioural Therapy and Mindfulness, have also been used to lems. Social activities, or thinking about relationships, can be help people change their thinking about social relation- overlooked in clinical consultations – in favour of medica- ships: some promising results have been reported, espe- tions or psychological therapies, and there have been recent cially with older adult populations [77]. Thus there are calls to raise the profile of social factors in mental health care approaches available with potential to be adapted and and mental health research [16]. Raising practitioners’ aware- tested for people with mental health problems, to try to al- ness of the beneficial effects of good perceived social support leviate the adverse effects identified in this paper. There is Wang et al. BMC Psychiatry (2018) 18:156 Page 14 of 16 also a need to consider public understanding of the im- Acknowledgments We are grateful for the help of UCL Library staff for consultation and portance of nurturing social relationships, as the high guidance in the search strategy. We would like to thank the authors of prevalence of loneliness is not only an individual but ne- screened papers who responded to our emails for their support. cessarily also a community and societal level problem. Authors’ contributions Thus people with mental health problems, like other SJ, JW and BLE conceived the review. SJ and BLE commented on search groups in the population who are vulnerable to the effects strategy and review protocol. JW developed the search strategy and review of loneliness, are likely to benefit from an approach to protocol, did the systematic search, and wrote the first draft and co-ordinated further drafts. JW and FM independently screened and selected papers for loneliness that also takes account of community resources inclusion, extracted data, and assessed the methodological quality of each and how they might be enhanced [78]. study. RM helped screen reference lists of included studies and extract data from relevant studies. SJ resolved queries about inclusion/exclusion and disagreements between JW and FM during the review process. SJ, BLE, FM, and RM contributed comments and suggestions to the drafts. All authors read and Conclusions approved the final manuscript. This systematic review has identified prospective studies in the area of loneliness/perceived social support and outcomes Ethics approval and consent to participate Not applicable. of mental health problems. We found substantial evidence that in depression, poorer perceived social support is associ- Competing interests ated with poorer outcomes in terms of symptoms, recovery The authors declare that they have no competing interests. and functioning. There is some preliminary evidence of a similar relationship in bipolar and anxiety disorders, and of a Publisher’sNote relationship between greater perceived social support and Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. better quality of life and functioning in schizophrenia. 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BMC PsychiatrySpringer Journals

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