The inflammatory and genetic mechanisms underlying the cumulative effect of co-occurring pain conditions on depression
Rongtao Jiang, Paul Geha, Matthew Rosenblatt, Yunhe Wang, Zening Fu, Maya Foster, Wei Dai, Vince D. Calhoun, 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, Marisa N. Spann, Dustin Scheinost
Abstract
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.