| BackgroundDepression has become one of the major global public health threats,with depression ranking 13th in the disease burden of all diseases and 1st in the disease burden of mental disorders in 2019.It is speculated that by 2030,depression will be the second leading cause of disease burden and disability worldwide.It affects up to 322 million people worldwide and can lead to many adverse outcomes,such as suicide,self-injury,and cardiovascular disease,as well as placing tremendous stress on patients’ families,health care providers,and socioeconomics.Despite advances in pharmacological and psychological treatment options for depression,the annual prevalence of depression in the Western world remains high.Therefore,it has become important to learn more about the potentially modifiable risk factors associated with depression.Loneliness is a subjective feeling of unmet social needs,loss of connection and lack of belonging,while social isolation is the objective limited or lack of social contact with others.Loneliness and social isolation were significant predictors of death.Previous studies have shown an association between loneliness and social isolation and the incidence of depression.However,most previous studies had focused only on loneliness or social isolation,or had combined the two into a single concept.Therefore,there is still uncertainty about whether there is an interaction between the two that affects the onset of depression.In addition,most studies on the relationship between loneliness,social isolation,and depression had used self-reported forms of depression rather than hospital diagnosis,which may be subject to information bias.Therefore,further research is needed to investigate the relationship between loneliness,social isolation and the onset of depression.AimsUsing follow-up data from the UK Biobank study,this study aimed to explore:1.The relationship between loneliness and the incidence of depression;2.The relationship between social isolation and depression incidence;3.The interactive effects of loneliness and social isolation on the risk of depression incidence.Methods1.Study subjectsThe study population was drawn from UK Biobank,which was a longitudinal study tracking the health status of more than 500,000 voluntary participants aged 38 to 79 years.Participants in the study were registered with the National Health System(NHS)in the UK and lived within 25 miles of the assessment center and signed informed consent.After excluding dropouts from follow-up,those with depression at baseline,those with deficits in loneliness and social isolation,and those with missing covariates,a total of 339051 individuals were included in this study.2,Statistical analysis(1)Baseline characteristics of the study subjects were statistically described according to the presence or absence of loneliness,and social isolation and depression,respectively.Continuous variables were expressed as medians(25th percentile,75th percentile)and the Mann-whitney U test was used to compare differences between groups.Categorical variables were expressed as frequency(percentage)and compared between groups by χ2 test.(2)The follow-up endpoint event in this study was depression incidence,and the followup period was calculated from the date of participation in the assessment center,and the observed endpoints were first diagnosis of depression,loss to follow-up,death,or end of current follow-up,whichever event occurred first.Cumulative incidence curves for the study population were plotted using the Kaplan-Meier method,and Log-Rank was used to test for differences in cumulative risk curves for the incidence of depression in the study population under different conditions of loneliness and social isolation.(3)Cox proportional risk regression models were used to assess the relationship between loneliness,social isolation and depression incidence,and subgroup analyzes of age,gender,race,smoking status,alcohol consumption frequency,and physical activity were conducted.Finally,we analyzed whether there were additive and multiplicative effects between loneliness and social isolation.In addition,sensitivity analysis was done excluding patients with depression incidence in the first year of follow-up.The results were presented as Hazard ratios(HR)with 95%confidence intervals(95%CI).Proportional risk assumption was tested using Schoenfeld residuals.All statistical analyzes were performed using SPSS 24.0(IBM Corp,Armonk,New York)and R 4.1.0 software(including the ’survival’ package,the ’interactionR’ package,’forestplot’package,and ’survminer’ package).Statistical tests were all performed using two-sided tests,and differences were considered statistically significant when P<0.05.Results1.Baseline characteristics of the study populationA total of 339051 study subjects were included in this study,with a median baseline age of 58 years.The minimum age was 38 years old and the maximum age was 73 years old.There were 164354 males(48.47%)and 174697 females(51.53%).The median follow-up time was 12.45 years(IQR:11.62-13.18),and the longest follow-up time was 15.16 years.Depression occurred in 13096 study subjects at the end of the study,with a cumulative incidence of 3.86%.The distribution of depression incidence was different among study subjects with different age,gender,race,region,body mass index,education level,employment status,Townsend deprivation index,smoking status,frequency of alcohol consumption,physical activity,and sleep duration,with statistically significant differences(P<0.05).2.The relationship between loneliness and the incidence of depressionThe incidence of depression among those with loneliness was 8.39%(1130/13475);while the incidence of depression among those without loneliness was 3.68%(11966/325576).LogRank test showed that the cumulative incidence of depression differed statistically significantly(P<0.001)among different loneliness conditions,with the group with loneliness being higher than the group without loneliness.Multivariable Cox regression showed that after adjusting for variables such as age,gender,smoking status and drinking frequency as well as social isolation,the risk of developing depression for people with loneliness was 1.77 times as high as in those without loneliness(HR=1.77,95%CI=1.67-1.89).Stratified analyzes showed that in the univariate model,having loneliness had a greater effect on the incidence of depression in men compared to those without loneliness(men:HR=2.64,95%CI=2.42-2.88),but after multivariable adjustment,it was found that differences were not statistically significant(P>0.05).3.The relationship between social isolation and incidence of depressionThe incidence of depression among socially isolated individuals was 5.58%(1557/27909);while the incidence of depression among those without social isolation was 3.71%(11539/311142).Log-Rank test showed that the difference in cumulative incidence of depression across social isolation was statistically significant(P<0.001),with the group with social isolation being higher than the group without social isolated group.The full model showed that the risk of developing depression for people with social isolation was 1.14 times as high as in those without social isolation(HR=1.14,95%CI=1.08-1.21).In the gender subgroup,the risk of depression incidence was 1.17 times(HR=1.17,95%CI=1.08-1.28)and 1.09 times(HR=1.09,95%CI=1.02-1.18)as high as in men and women with social isolation than without social isolation,respectively,with a larger effect in men(Pinteraction<0.05).4.The interaction effect of loneliness and social isolationUsing no loneliness and no social isolation as a reference,the risk of depression in those with social isolation was 1.16 times as high as in those without social isolation in the absence of loneliness,that is,the main effect of social isolation was HR=1.16(95%CI:1.10-1.24).In the absence of social isolation,the risk of depression in those with loneliness was 1.83 times as high as in those without loneliness,that is,the main effect of loneliness was HR=1.83(95%CI:1.70-1.96).There was no additive interaction between loneliness and social isolation.After controlling for covariates such as gender,region,race,smoking status,and physical activity,the interaction term for loneliness and social isolation was included in the model,and it was found that loneliness and social isolation still increased the risk of depression(loneliness:HR=1.83,95%CI=1.70-1.96;social isolation:HR=1.16,95%CI=1.10-1.24),but the multiplicative term of loneliness and social isolation was not statistically significant(HR=0.89,95%CI=0.77-1.03).5.Sensitivity analysisAfter excluding newly depressed patients in the first year of follow-up,both loneliness and social isolation increased the risk of depression(P<0.05),but there was no additive or multiplicative interaction between loneliness and social isolation(P>0.05).Conclusions1.Both loneliness and social isolation are risk factors for the incidence of depression.2.The modifying effect of gender on the degree of association between social isolation and the risk of developing depression was more significant in men,but no modifying effect of age,race,smoking status,frequency of alcohol consumption,and physical activity was found.3.There was no interaction effect of loneliness and social isolation on the risk of depression incidence. |
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