Cytokines as Biomarkers in Psychiatric Disorders: Methodological Issues

In contrast to other fields of medicine, and despite extensive research to identify neuroimaging, electroencephalography, or blood-based biomarkers, neither trait nor state biomarkers are currently available in psychiatry. Would such biomarkers be available, they could help clinicians to answer some of the simplest questions to which they are faced in their daily practice. Previous studies have shown that most severe mental disorders are associated with altered blood levels of cytokines, a group of small soluble proteins that are mainly produced by immune cells. Because cytokine levels can be measured using sensitive and cost-effective analytical methods, many authors have investigated whether they could be useful biomarkers in psychiatry. Despite hundreds of papers in this field, no single cytokine, or combination of cytokines, has emerged as a biomarker that would be robust enough to be used in clinical settings. Here, we will argue that this failure may have been due at least in part to overlooked methodological issues not only for preparation, storage, and analysis of the biological samples but also for statistical analysis of the datasets. We will also propose some guidelines for future studies and advocate for the adoption of common Standard Operating Procedures.