On the transdiagnostic nature of peripheral biomarkers in major psychiatric disorders: a systematic review

Abstract

The search for biomarkers has been one of the leading endeavors in biological psychiatry; nevertheless, in spite of hundreds of publications, it has yet to make an impact in clinical practice. To study how biomarker research has progressed over the years, we performed a systematic review of the literature to evaluate (a) the most studied peripheral molecular markers in major psychiatric disorders, (b) the main features of studies in which they are proposed as biomarkers and (c) whether their patterns of variation are similar across disorders. Out of the six molecules most commonly present as keywords in articles studying plasmatic markers of schizophrenia, major depressive disorder or bipolar disorder, five (BDNF, TNF-alpha, IL-6, C-reactive protein and cortisol) were the same across the three diagnoses. An analysis of the literature on these molecules showed that, while 65% of studies were cross-sectional and 66% compared biomarker levels between patients and controls in specific disorders, only 10% presented an objective measure of diagnostic or prognostic efficacy. Meta-analyses showed that variation in the levels of these molecules was robust across studies, but also similar among disorders, suggesting them to reflect transdiagnostic systemic consequences of psychiatric illness rather than diagnostic markers. Based on this, we discuss how current publication practices have led to research fragmentation across diagnoses, and what steps can be taken in order to increase clinical translation in the field.