Evidence map›Paper›PMID 41205074›Full record

ArticleEuropean archives of psychiatry and clinical neuroscience2026

Identification of genetic associations and key influences contributing to the pathway from social isolation or loneliness to depression.

Wenxi Sun, Chao Sun, Haonan Zhang, Ping Sun, Huihui Song, Xiaohui Wu, Jun Chen, Yiru Fang, Xiaobin Zhang

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Article in European archives of psychiatry and clinical neuroscience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

9 authors.

Wenxi SunSuzhou Guangji Hospital, Suzhou, Jiangsu Province, China.
Chao SunSuzhou Guangji Hospital, Suzhou, Jiangsu Province, China.
Haonan ZhangClinical Research Center, Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China.
Ping SunQingdao Mental Health Center, Qingdao, 266034, China.
Huihui SongSuzhou Guangji Hospital, Suzhou, Jiangsu Province, China.
Xiaohui WuClinical Research Center, Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China.
Jun ChenClinical Research Center, Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China.
Yiru FangClinical Research Center, Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China.
Xiaobin ZhangSuzhou Guangji Hospital, Suzhou, Jiangsu Province, China. Zhangxiaobim@163.com.ORCID http://orcid.org/0000-0002-0577-5951

Funding

Geriatric Research Education and Clinical Center SZXK202116Key Laboratory in Science and Technology Development Project of Suzhou SZS2024016National Mentorship Training Program for Young Health Professionals in Suzhou Qngg2022027Science and Technology Commission of Shanghai Municipality 2018SHZDZX05Suzhou clinical Medical Center for mood disorders Szlcyxzx202109Suzhou Key Technologies Program SKY2021063Suzhou Science and Technology Development Programme Youth Project SKYD2023160
6 · The paper itself

Abstract

backgroundObservational studies have found isolation or loneliness to be associated with depression. However, the causal relationship between isolation or loneliness and depression, as well as the mediating factors involved, remains unclear.

methodsThis study aims to establish the causal effects of social isolation and loneliness on depression and to identify key mediators using a two-sample Mendelian randomization (MR) approach. Using genetic variants from the UK Biobank (N = 455,364 for social isolation/loneliness; N = 462,933 for depression), we applied univariate and multivariate MR (UVMR and MVMR) to assess causal relationships and mediation effects.

resultsGenetically predicted social isolation and loneliness (β = 0.188, 95% CI 0.109, 0.268, P = 3.594e-06) were significantly associated with increased depression levels. Of the 25 potential risk factors for depression, two were identified as mediators of the relationship between isolation, loneliness, and depression: neuroticism (mediation ratio: 54.3% [95% CI: 43.1%, 65.5%]) and insomnia (15.5% [95% CI: 7.7%, 23.3%]). Multiple sensitivity analyses confirmed the robustness of the findings.

conclusionThis study provides genetic evidence that social isolation and loneliness causally contribute to increased depression risk, with neuroticism and insomnia as key mediators, though generalizability to non-European populations requires further investigation.

Indexed as

DepressionLonelinessSocial IsolationAgedFemaleHumansMaleMendelian Randomization AnalysisMiddle AgedNeuroticismUnited KingdomCausalityDepressionMediation analysesMendelian randomizationNeuroticismSleeplessnessSocial isolation

Identifiers

PMID41205074

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.