The literature on non-genetic peripheral
biomarkers for major
mental disorders is broad, with conflicting results. An umbrella review of meta-analyses of non-genetic peripheral
biomarkers for
Alzheimer's disease,
autism spectrum disorder,
bipolar disorder (BD),
major depressive disorder, and
schizophrenia, including first-episode
psychosis. We included meta-analyses that compared alterations in peripheral
biomarkers between participants with
mental disorders to controls (i.e., between-group meta-analyses) and that assessed
biomarkers after treatment (i.e., within-group meta-analyses). Evidence for association was hierarchically graded using a priori defined criteria against several biases. The Assessment of Multiple Systematic Reviews (AMSTAR) instrument was used to investigate study quality. 1161 references were screened. 110 met inclusion criteria, relating to 359 meta-analytic estimates and 733,316 measurements, on 162 different
biomarkers. Only two estimates met a priori defined criteria for convincing evidence (elevated awakening
cortisol levels in euthymic BD participants relative to controls and decreased
pyridoxal levels in participants with
schizophrenia relative to controls). Of 42 estimates which met criteria for highly suggestive evidence only five
biomarker aberrations occurred in more than one disorder. Only 15 meta-analyses had a power >0.8 to detect a small effect size, and most (81.9%) meta-analyses had high heterogeneity. Although some associations met criteria for either convincing or highly suggestive evidence, overall the vast literature of peripheral
biomarkers for major
mental disorders is affected by bias and is underpowered. No convincing evidence supported the existence of a trans-diagnostic
biomarker. Adequately powered and methodologically sound future large collaborative studies are warranted.