Exploring the multiverse: the impact of researchers' analytic decisions on relationships between depression and inflammatory markers

Neuropsychopharmacology. 2023 Sep;48(10):1465-1474. doi: 10.1038/s41386-023-01621-4. Epub 2023 Jun 19.


In recent years, a replication crisis in psychiatry has led to a growing focus on the impact of researchers' analytic decisions on the results from studies. Multiverse analyses involve examining results across a wide array of possible analytic decisions (e.g., log-transforming variables, number of covariates, or treatment of outliers) and identifying if study results are robust to researchers' analytic decisions. Studies have begun to use multiverse analysis for well-studied relationships that have some heterogeneity in results/conclusions across studies.We examine the well-studied relationship between peripheral inflammatory markers (PIMs; e.g., white blood cell count (WBC) and C-reactive protein (CRP)) and depression severity in the large NHANES dataset (n = 25,962). Specification curve analyses tested the impact of 9 common analytic decisions (comprising of 58,000+ possible combinations) on the association of PIMs and depression severity. Relationships of PIMs and total depression severity are robust to analytic decisions (based on tests of inference jointly examining effect sizes and p-values). However, moderate/large differences are noted in effect sizes based on analytic decisions and the majority of analyses do not result in significant findings, with the percentage of analyses with statistically significant results being 46.1% for WBC and 43.8% for CRP. For associations of PIMs with specific symptoms of depression, some associations (e.g., sleep, appetite) in males (but not females) were robust to analytic decisions. We discuss how multiverse analyses can be used to guide research and also the need for authors, reviewers, and editors to incorporate multiverse analyses to enhance replicability of research findings.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • C-Reactive Protein*
  • Depression*
  • Humans
  • Male
  • Nutrition Surveys


  • C-Reactive Protein