Sir,
Kozak et al.[1] studied inflammatory markers in patients with acute ischemic stroke who did versus did not have preexisting major depression. Surprisingly, although inflammatory marker levels have consistently been shown to be elevated in major depression, they failed to replicate differences in levels between the two groups of patients. We believe that their methods may have had two potentially fatal limitations. Early elevations in inflammatory markers are linked to underlying stroke severity,[2,3] and inflammatory markers may reach ceiling levels at higher stroke severities.[4] Because blood for cytokine measurement was collected within 24 h of stroke onset, and because the study was conducted on inpatients who probably had severe stroke, on both counts a ceiling effect in inflammatory marker levels might have prevented differentiation of the depressed and nondepressed groups.
We add that the study had other limitations. Although this was projected as a hypothesis-testing study,[5] the authors did not define primary and secondary outcomes; in fact, they stated different hypotheses in different places in the article and generally tested all measured variables between depressed and nondepressed groups as in an exploratory study. Furthermore, the absence of power calculations suggests a lack of planning and a vulnerability to a Type II statistical error. Finally, there is a curious statement that psychiatrists were blinded to the neuropsychiatric evaluations; how can this be possible when the very act of assessment prevents blinding?
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Conflicts of interest
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REFERENCES
- 1.Kozak HH, Uǧuz F, Kılınç İ, Uca AU, Tokgöz OS, Güney F, et al. A cross-sectional study to assess the association between major depression and inflammatory markers in patients with acute ischemic stroke. Indian J Psychiatry. 2019;61:283–9. doi: 10.4103/psychiatry.IndianJPsychiatry_175_18. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Doll DN, Barr TL, Simpkins JW. Cytokines: Their role in stroke and potential use as biomarkers and therapeutic targets. Aging Dis. 2014;5:294–306. doi: 10.14336/AD.2014.0500294. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Montaner J, Fernandez-Cadenas I, Molina CA, Ribó M, Huertas R, Rosell A, et al. Poststroke C-reactive protein is a powerful prognostic tool among candidates for thrombolysis. Stroke. 2006;37:1205–10. doi: 10.1161/01.STR.0000217744.89208.4e. [DOI] [PubMed] [Google Scholar]
- 4.Whiteley W, Jackson C, Lewis S, Lowe G, Rumley A, Sandercock P, et al. Inflammatory markers and poor outcome after stroke: A prospective cohort study and systematic review of interleukin-6. PLoS Med. 2009;6:e1000145. doi: 10.1371/journal.pmed.1000145. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Andrade C. Describing research design. Indian J Psychol Med. 2019;41:201–2. doi: 10.4103/IJPSYM.IJPSYM_66_19. [DOI] [PMC free article] [PubMed] [Google Scholar]