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.

Histone methylation at H3K9: Evidence for a restrictive epigenome in schizophrenia

“…While postmortem investigations are able to serve as a useful snapshot at the time of death, the ability to measure and monitor histone marks over time as marker of disease progression, improvement, or as a predictor of pharmacological response are only possible using peripheral blood cells. A strong rationale for the use of blood chromatin ‘levels’ as a type of biosensor that registers the epigenetic milieu has been proposed elsewhere (Sharma 2012). Furthermore, previous studies have indicated the mRNA patterns of expression patterns in lymphocytes are capable of distinguishing between psychiatric diagnostic groups (Middleton et al 2005).…”

The Relationship between DNA Methylation and Antidepressant Medications: A Systematic Review

“…Peripheral blood mononuclear cells (PBMC) have been used as a proxy for central nervous system (CNS) tissue. PBMC are non-invasive to collect from living subjects and serve as surrogates for brain tissue molecular changes, though there can be limited coherence between PBMC and CNS biomarkers in various circumstances [47,48]. D'Addario et al 2012 examined antidepressant effects on BDNF DNA methylation using PBMC from forty-nine human subjects diagnosed with bipolar disorder type 1 (BD1), forty-five subjects with bipolar disorder type 2 (BD2), and fifty-two healthy controls (HC) [49].…”

Histone H3 phosphorylation is upregulated in PBMCs of schizophrenia patients in comparison to healthy controls

“…An ELISA kit was used to measure H3S10phos (Active Motif #53111) as well as Total H3 (#53110) from acid histone extracts of PBMC from human subjects (Sharma et al, 2006; Sharma, 2012; Chase et al, 2015). Samples were measured in duplicate using a 96-well format with multiple controls: 1) a standard curve; 2) plate-control (invariant sample); and 3) randomized and blinded plate position.…”