Peripheral Biomarkers Revisited: Integrative Profiling of Peripheral Samples for Psychiatric Research

Abstract

Peripheral samples, such as blood and skin, have been used for decades in psychiatric research as surrogates for central nervous system samples. Although the validity of the data obtained from peripheral samples has been questioned and other state-of-the-art techniques, such as human brain imaging, genomics, and induced pluripotent stem cells, seem to reduce the value of peripheral cells, accumulating evidence has suggested that revisiting peripheral samples is worthwhile. Here, we re-evaluate the utility of peripheral samples and argue that establishing an understanding of the common signaling and biological processes in the brain and peripheral samples is required for the validity of such models. First, we present an overview of the available types of peripheral cells and describe their advantages and disadvantages. We then briefly summarize the main achievements of omics studies, including epigenome, transcriptome, proteome, and metabolome analyses, as well as the main findings of functional cellular assays, the results of which imply that alterations in neurotransmission, metabolism, the cell cycle, and the immune system may be partially responsible for the pathophysiology of major psychiatric disorders such as schizophrenia. Finally, we discuss the future utility of peripheral samples for the development of biomarkers and tailor-made therapies, such as multimodal assays that are used as a battery of disease and trait pathways and that might be potent and complimentary tools for use in psychiatric research.

Biomarkers in schizophrenia: A focus on blood based diagnostics and theranostics

“…Sz is a psychiatric disorder and there have been great efforts to the study of potential neuronal and glial abnormalities that may provide the basis of the aetiology of the disorder. However, findings from such studies have not yet been translated into biomarkers that are practical in clinical use [4] because brain biopsies are not acceptable and neuroimaging techniques are expensive [5] and the results are inconclusive. Thus, in recent years, there has been search for bloodbased biomarkers for Sz as a valid alternative [5,6] .…”

“…However, findings from such studies have not yet been translated into biomarkers that are practical in clinical use [4] because brain biopsies are not acceptable and neuroimaging techniques are expensive [5] and the results are inconclusive. Thus, in recent years, there has been search for bloodbased biomarkers for Sz as a valid alternative [5,6] . Bloodbased biomarkers are regarded as a feasible option because the dysregulation of gene expression, epigenetic patterns, protein quantities, metabolic and inflammatory molecules in peripheral blood have been shown to have distinct patterns in people with Sz [4,5,711] .…”

“…Thus, in recent years, there has been search for bloodbased biomarkers for Sz as a valid alternative [5,6] . Bloodbased biomarkers are regarded as a feasible option because the dysregulation of gene expression, epigenetic patterns, protein quantities, metabolic and inflammatory molecules in peripheral blood have been shown to have distinct patterns in people with Sz [4,5,711] . In addition, the strong heritability of Sz suggests that there may be genetic markers detectable in peripheral tissue [12] .…”

Circulating biomarkers in schizophrenia: a proteomics perspective

“…As shown in Table 2, blood-based analysis account for the majority of such studies, especially with the analysis of serum and plasma, although blood cells' analysis is growing in interest ( Table 3) [74]. The rationale behind this is that, even if psychiatric disorders are brain diseases, its consequences can be detected throughout the entire body; and, most importantly, the access to fluids like blood is considerably easier than the access to the living brain or even to CSF.…”

“…It has been demonstrated that there are dynamic changes correlating changes in brain and blood and vice-versa [47,74], and, in the case of SCZ, some changes in hormones, cytokines or growth factors can be replicated both in brain and blood stream [74,76].…”