Blood Chromatin as a Biosensor of the Epigenetic Milieu: A Tool for Studies in Living Psychiatric Patients

Abstract

This article constructs an argument for using blood chromatin (contained in nucleated blood cells) as a protein biosensor to integrate the ambient epigenetic influences in the internal milieu. An analogy is made to blood glycated hemoglobin (HbA1c) in diabetes as an integrated proxy for glucose levels and body-wide protein glycation. Genome-wide chromatin can serve as an organizing principle that bridges the central and peripheral compartments by entraining commensurable gene networks. Chromatin deposition along these networks will be imposed by the totality of epigenetic influences, which incorporates significant contributions from biochemicals that readily traverse the blood-brain barrier. In a clinical trial, these influences would be dominated by pharmaceuticals designed to override pathophysiological signals. In practice, mRNA readouts would be limited to nonsynaptic gene networks whose critical nodes are occupied by a site-specific chromatin modification. Finally, chromatin measurements in peripheral tissue will retain the influences of a patient's lifestyle and unique genomic background.