1. Elevated brain-derived cell-free DNA among patients with first psychotic episode - a proof-of-concept study
- Author
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Ilana Pelov, Asael Lubotzky, Ronen Teplitz, Daniel Neiman, Adama Smadja, Hai Zemmour, Sheina Piyanzin, Bracha-Lea Ochana, Kirsty L Spalding, Benjamin Glaser, Ruth Shemer, Yuval Dor, and Yoav Kohn
- Subjects
Genetic Markers ,General Immunology and Microbiology ,Psychotic Disorders ,General Neuroscience ,Biomarkers, Tumor ,Brain ,Humans ,General Medicine ,DNA Methylation ,Cell-Free Nucleic Acids ,General Biochemistry, Genetics and Molecular Biology - Abstract
BackgroundSchizophrenia is a common, severe and debilitating psychiatric disorder. Despite extensive research there is as yet no biological marker that can aid in its diagnosis and course prediction. This precludes early detection and intervention. Imaging studies suggest brain volume loss around the onset and over the first few years of schizophrenia, and apoptosis has been proposed as the underlying mechanism. Cell free DNA fragments (cfDNA) are released into the bloodstream following cell death. Tissue-specific methylation patterns allow the identification of the tissue origins of cfDNA.MethodsWe developed a cocktail of brain specific DNA methylation markers, and used it to assess the presence of brain-derived cfDNA in the plasma of patients with a first psychotic episode.ResultsWe detected significantly elevated neuron- (p=0.0013), astrocyte- (p=0.0016), oligodendrocyte- (p=0.0129) and whole brain-derived (p=0.0012) cfDNA in the plasma of patients during their first psychotic episode (n=29), compared with healthy controls (n=31). Increased cfDNA levels were not correlated with psychotropic medications use. Area Under the Curve (AUC) was 0.77, with 65% sensitivity at 90% specificity in patients with a psychotic episode.ConclusionsPotential interpretations of these findings include increased brain cell death, disruption of the blood brain barrier or a defect in clearance of material from dying brain cells. Brain-specific cfDNA methylation markers can potentially assist early detection and monitoring of schizophrenia and thus allow early intervention and adequate therapy.
- Published
- 2021