Association between social isolation and depression: Evidence from longitudinal and Mendelian randomization analyses

Increasing evidence shows that social isolation and depression are likely to interact with each other, yet the direction and causality of the association are not clear. This study aims to examine the possible reciprocity in the relationship between social isolation and depression. This study fitted a cross-lagged panel model (CLPM) by using data from the English Longitudinal Study of Aging (ELSA, 2014–2019, n = 6787) to examine the temporal relationship between social isolation and depressive symptoms in older adults. We then conducted two-sample bidirectional Mendelian randomization (MR) analyses by using independent genetic variants associated with multiple social isolation phenotypes (n = 448,858-487,647) and with depression (n = 215,644-2,113,907) as genetic instruments from genome-wide association studies to assess the causality between social isolation and onset of depression. The CLPM in the ELSA cohort showed a significant and positive lagged effect of social isolation on depressive symptoms (β = 0.037, P < .001). The reverse cross-lagged path from depressive symptoms to social isolation was also statistically significant (β = 0.039, P < .001). In two-sample bidirectional MR, the genetically predicted loneliness and social isolation combined phenotype (LNL-ISO) was positively associated with occurrence of depression (OR = 1.88, 95 % CI: 1.41–2.50, P < .001), vice versa (OR = 1.16, 95 % CI:1.13–1.20, P < .001). The self-report nature of the assessments and missing data are study limitations. These findings suggest a bidirectional relationship between social isolation and depression. It is important to develop interventions that highlight the reciprocal consequences of improving either mental health or social connection in older adults.