Sex differences in the inflammation-depression link: A systematic review and meta-analysis
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Bibliographic record
Abstract
Major Depressive Disorder (MDD) is a heterogeneous disorder that affects twice as many women than men. Precluding advances in more tailored and efficacious treatments for depression is the lack of reliable biomarkers. While depression is linked to elevations in inflammatory immune system functioning, this relationship is not evident among all individuals with depression and may vary based on symptom subtypes and/or sex. This systematic review and meta-analysis examined whether inflammatory immune peripheral markers of depression are sex-specific. PRISMA guidelines were followed for the systematic review, and a comprehensive search strategy that identified studies from PubMed and PsycInfo was applied. Studies were included if they reported C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α and/or IL-1β for males and/or females among depressed and healthy adults. We identified 23 studies that satisfied these inclusion criteria. Random-effects meta-analysis models were fit, and measures of association were summarized between levels of circulating markers of inflammation in depressed and healthy males and females. Sex-based analyses revealed elevated levels of CRP among females with depression (Cohen's d = 0.19) relative to their healthy counterparts (p = 0.02), an effect not apparent among males (Cohen's d = -0.01). Similarly, levels of IL-6 were increased among females with depression compared to healthy controls (Cohen's d = 0.51; p = 0.04), but once again this was not found among males (Cohen's d = 0.16). While TNF-α levels were elevated among individuals with depression compared to controls (p = 0.01), no statistically significant sex differences were found. The meta-analysis for IL-1β resulted in only three articles, and thus, results are presented in the supplemental section. This meta-analysis advances our understanding of the unique involvement of inflammatory biomarkers in depression among men and women, which may help inform more tailored sex-specific treatment approaches in the future.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.004 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it