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Biol Psychiatry. 2014 Jun 15;75(12):920-8. doi: 10.1016/j.biopsych.2013.09.035. Epub 2013 Oct 18.

Peripheral biomarkers revisited: integrative profiling of peripheral samples for psychiatric research.

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Laboratory of Structural Physiology, Center for Disease Biology and Integrative Medicine, University of Tokyo, Tokyo; Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama, Japan. Electronic address:
Department of Psychiatry and Human Behavior, Functional Genomics Laboratory, University of California, Irvine, California.
Department of Molecular Psychiatry, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.


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.


Biomarker; diagnostic support; functional assay; omics; peripheral sample; tailor-made therapy

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