Loneliness, Anxiety Symptoms, Depressive Symptoms, and Suicidal Ideation in the All of Us Dataset

Importance: Although anxiety symptoms and depressive symptoms are linked with increases in suicidal ideation, they leave much of the variance in suicidal ideation unexplained. Loneliness may mediate the links between anxiety symptoms and suicidal ideation as well as depressive symptoms and suicidal ideation. Objective: To analyze the mediating role of loneliness in the association between anxiety symptoms and suicidal ideation as well as in the association between depressive symptoms and suicidal ideation. Design, Setting, and Participants: This cross-sectional study used data collected between May 31, 2017, and October 1, 2023, from 62 685 US adults who completed the self-report mental health survey portion of the National Institutes of Health's All of Us Research Program. Main Outcomes and Measures: Self-report surveys estimated anxiety symptoms (using the 7-item Generalized Anxiety Disorder scale), depressive symptoms (using the first 8 items of the 9-item Patient Health Questionnaire [PHQ-9]), loneliness (using the UCLA Loneliness Scale), and suicidal ideation (using item 9 of the PHQ-9). Analyses were conducted in August of 2025. Results: The analytic sample of 62 685 individuals had a mean (SD) age of 61.8 (16.1) years and included 40 749 women (65.0%). Anxiety symptoms (r = 0.33; P < .001), depressive symptoms (r = 0.39; P < .001), and loneliness (r = 0.31; P < .001) correlated with suicidal ideation. When controlling for gender and race and ethnicity, depressive symptoms (B = 0.017 [95% CI, 0.017-0.019]), anxiety symptoms (B = 0.004 [95% CI, 0.004-0.006]), and loneliness (B = 0.007 [95% CI, 0.007-0.008]) accounted for significant variability in suicidal ideation. Loneliness partially mediated the association between anxiety symptoms (average causal mediation effect = 0.01; proportion mediated, 0.25; total association, 0.03; P < .001) and suicidal ideation as well as depressive symptoms (average causal mediation effect = 0.003; proportion mediated, 0.10; total association, 0.02; P < .001) and suicidal ideation, indicating the associations of anxiety and depressive symptoms with suicidal ideation were in part mediated by loneliness. Conclusions and Relevance: In this cross-sectional study of 62 685 participants from the All of Us Research Program, loneliness partially mediated the association between anxiety symptoms and suicidal ideation as well as depressive symptoms and suicidal ideation. Targeting and reducing loneliness may present a transdiagnostic approach to arrest the progression from anxiety and depressive symptoms toward suicidal ideation.