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Elevated brain-derived cell-free DNA among patients with first psychotic episode – a proof-of-concept study

Schizophrenia 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 a...

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Autores principales: Lubotzky, Asael, Pelov, Ilana, Teplitz, Ronen, Neiman, Daniel, Smadja, Adama, Zemmour, Hai, Piyanzin, Sheina, Ochana, Bracha-Lea, Spalding, Kirsty L, Glaser, Benjamin, Shemer, Ruth, Dor, Yuval, Kohn, Yoav
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9203052/
https://www.ncbi.nlm.nih.gov/pubmed/35699419
http://dx.doi.org/10.7554/eLife.76391
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author Lubotzky, Asael
Pelov, Ilana
Teplitz, Ronen
Neiman, Daniel
Smadja, Adama
Zemmour, Hai
Piyanzin, Sheina
Ochana, Bracha-Lea
Spalding, Kirsty L
Glaser, Benjamin
Shemer, Ruth
Dor, Yuval
Kohn, Yoav
author_facet Lubotzky, Asael
Pelov, Ilana
Teplitz, Ronen
Neiman, Daniel
Smadja, Adama
Zemmour, Hai
Piyanzin, Sheina
Ochana, Bracha-Lea
Spalding, Kirsty L
Glaser, Benjamin
Shemer, Ruth
Dor, Yuval
Kohn, Yoav
author_sort Lubotzky, Asael
collection PubMed
description Schizophrenia 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 (cfDNA) fragments are released into the bloodstream following cell death. Tissue-specific methylation patterns allow the identification of the tissue origins of cfDNA. We 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. We 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. Potential 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.
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spelling pubmed-92030522022-06-17 Elevated brain-derived cell-free DNA among patients with first psychotic episode – a proof-of-concept study Lubotzky, Asael Pelov, Ilana Teplitz, Ronen Neiman, Daniel Smadja, Adama Zemmour, Hai Piyanzin, Sheina Ochana, Bracha-Lea Spalding, Kirsty L Glaser, Benjamin Shemer, Ruth Dor, Yuval Kohn, Yoav eLife Genetics and Genomics Schizophrenia 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 (cfDNA) fragments are released into the bloodstream following cell death. Tissue-specific methylation patterns allow the identification of the tissue origins of cfDNA. We 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. We 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. Potential 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. eLife Sciences Publications, Ltd 2022-06-14 /pmc/articles/PMC9203052/ /pubmed/35699419 http://dx.doi.org/10.7554/eLife.76391 Text en © 2022, Lubotzky, Pelov et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Genetics and Genomics
Lubotzky, Asael
Pelov, Ilana
Teplitz, Ronen
Neiman, Daniel
Smadja, Adama
Zemmour, Hai
Piyanzin, Sheina
Ochana, Bracha-Lea
Spalding, Kirsty L
Glaser, Benjamin
Shemer, Ruth
Dor, Yuval
Kohn, Yoav
Elevated brain-derived cell-free DNA among patients with first psychotic episode – a proof-of-concept study
title Elevated brain-derived cell-free DNA among patients with first psychotic episode – a proof-of-concept study
title_full Elevated brain-derived cell-free DNA among patients with first psychotic episode – a proof-of-concept study
title_fullStr Elevated brain-derived cell-free DNA among patients with first psychotic episode – a proof-of-concept study
title_full_unstemmed Elevated brain-derived cell-free DNA among patients with first psychotic episode – a proof-of-concept study
title_short Elevated brain-derived cell-free DNA among patients with first psychotic episode – a proof-of-concept study
title_sort elevated brain-derived cell-free dna among patients with first psychotic episode – a proof-of-concept study
topic Genetics and Genomics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9203052/
https://www.ncbi.nlm.nih.gov/pubmed/35699419
http://dx.doi.org/10.7554/eLife.76391
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