Association of chronic pain with suicide attempt and death by suicide: A two-sample Mendelian randomization
Bibliographic record
Abstract
Abstract Prior studies have suggested an association between chronic pain and suicidal behavior. However, evidence supporting the causal nature of this association, and the role played by depression, remain difficult to establish due to confounding. We investigated associations of chronic pain with suicide attempt and death by suicide as well as the mediating role of depression in this association using a genetically informed method strengthening causal inference. We conducted a two-sample Mendelian randomization. Independent SNPs (N=97) from the Multisite Chronic Pain GWAS (NGWAS=387,649) were used as instrumental variables to test associations of chronic pain with suicide attempt (measured from hospital records; NGWAS=50,264) and death by suicide (measured from official death causes; NGWAS=18,085). Indirect associations of chronic pain with suicide attempt and death by suicide via major depressive disorder (NGWAS=173,005) were estimated. Primary analyses were supported by a range of sensitivity and outlier analyses.We found evidence supporting the contribution of chronic pain to increasing the risk of suicide attempt (OR=1.67, CI=1.21-2.35) and death by suicide (OR=2.00, CI=1.10-3.62). Associations were consistent across sensitivity analysis methods, and no evidence for outliers driving these associations was found. Through mediation analyses, we found that major depressive disorder explained a substantial proportion of the association between chronic pain and suicide attempt (proportion mediated=39%; ORindirect association=1.32, CI=1.09-1.61) and death by suicide (proportion mediated=34%; ORindirect association=1.40, CI=1.13-1.73). Our findings suggest that both pain management interventions and prevention of depression are likely to be effective strategies to reduce suicide risk in individuals with chronic pain.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.044 | 0.075 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.003 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".