The inflammatory and genetic mechanisms underlying the cumulative effect of co-occurring pain conditions on depression
Chronic pain conditions frequently coexist and share common genetic vulnerabilities. Despite evidence showing associations between pain and depression, the additive effect of co-occurring pain conditions on depression risk and the underlying mechanisms remain unclear. Leveraging data from 431,038 UK Biobank participants with 14-year follow-up, we found a significantly increased risk of depression incidence in individuals reporting pain, irrespective of body site or duration (acute or chronic), compared with pain-free individuals. The depression risk increased with the number of co-occurring pain sites. Mendelian randomization supported potential causal inference. We constructed a composite pain score by combining individual effects of acute or chronic pain conditions across eight body sites in a weighted manner. We found that depression risks increased monotonically in parallel with composite pain scores. Moreover, some inflammatory markers, including C-reactive protein, partially mediated the association between composite pain scores and depression risk. Considering the high prevalence of comorbid depression and pain, pain screening may help identify high-risk individuals for depression.
Authors
- Rongtao Jiang (ORCID: https://orcid.org/0000-0003-4657-0079)
- Paul Geha (ORCID: https://orcid.org/0000-0002-0537-7216)
- Zening Fu (ORCID: https://orcid.org/0000-0002-1591-4900)
- Dustin Scheinost (ORCID: https://orcid.org/0000-0002-6301-1167)
- Vince D. Calhoun (ORCID: https://orcid.org/0000-0001-9058-0747)
- Wei Dai (ORCID: https://orcid.org/0000-0002-1921-4100)
- Marisa N. Spann (ORCID: https://orcid.org/0000-0001-6162-9521)
- Matthew Rosenblatt (ORCID: https://orcid.org/0000-0002-3894-6198)
- Jing Sui （Beijing Normal University）， my correct affiliation is beijing normal university, not Qingdao University of Science and Technology, please correct the current affiliation. Thank you (ORCID: https://orcid.org/0000-0001-6837-5966)
- Maya Foster (ORCID: https://orcid.org/0000-0002-1617-1811)
- Yunhe Wang (ORCID: https://orcid.org/0000-0002-0923-1441)
Institutions
- Georgia Institute of Technology (US)
- Emory University (US)
- Georgia State University (US)
- Beijing Normal University (CN)
- Columbia University Irving Medical Center (US)
- University of Rochester Medical Center (US)
- Yale University (US)
- University of Oxford (GB)
- Center for Translational Research in Neuroimaging and Data Science (US)
Publication Details
- Journal
- Science Advances
- Published
- 2025-04-02
- DOI
- https://doi.org/10.1126/sciadv.adt1083
- Citations
- 19
- Primary Topic
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Type
- article
- Field-Weighted Citation Impact
- 27.95