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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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-06-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/76391 |
| _version_ | 1818026210620342272 |
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| author | Asael Lubotzky Ilana Pelov Ronen Teplitz Daniel Neiman Adama Smadja Hai Zemmour Sheina Piyanzin Bracha-Lea Ochana Kirsty L Spalding Benjamin Glaser Ruth Shemer Yuval Dor Yoav Kohn |
| author_facet | Asael Lubotzky Ilana Pelov Ronen Teplitz Daniel Neiman Adama Smadja Hai Zemmour Sheina Piyanzin Bracha-Lea Ochana Kirsty L Spalding Benjamin Glaser Ruth Shemer Yuval Dor Yoav Kohn |
| author_sort | Asael Lubotzky |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-10T04:28:23Z |
| format | Article |
| id | doaj.art-99c557cbe6234e8c8dd6f08840d16183 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T04:28:23Z |
| publishDate | 2022-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-99c557cbe6234e8c8dd6f08840d161832022-12-22T02:02:14ZengeLife Sciences Publications LtdeLife2050-084X2022-06-011110.7554/eLife.76391Elevated brain-derived cell-free DNA among patients with first psychotic episode – a proof-of-concept studyAsael Lubotzky0https://orcid.org/0000-0002-0460-0084Ilana Pelov1Ronen Teplitz2Daniel Neiman3Adama Smadja4Hai Zemmour5Sheina Piyanzin6Bracha-Lea Ochana7Kirsty L Spalding8Benjamin Glaser9https://orcid.org/0000-0003-4711-5000Ruth Shemer10Yuval Dor11https://orcid.org/0000-0003-2456-2289Yoav Kohn12https://orcid.org/0000-0003-0476-9610Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, the Hebrew University-Hadassah Medical School, Jerusalem, Israel; Neuropediatric Unit, Shaare Zedek Medical Center, Jerusalem, IsraelJerusalem Mental Health Center, Eitanim Psychiatric Hospital, Jerusalem, IsraelJerusalem Mental Health Center, Eitanim Psychiatric Hospital, Jerusalem, IsraelDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, the Hebrew University-Hadassah Medical School, Jerusalem, IsraelHebrew University-Hadassah School of Medicine, Jerusalem, IsraelDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, the Hebrew University-Hadassah Medical School, Jerusalem, IsraelDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, the Hebrew University-Hadassah Medical School, Jerusalem, IsraelDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, the Hebrew University-Hadassah Medical School, Jerusalem, IsraelKarolinska Institute, Department of Cell and Molecular Biology Stockholm, Stockholm, SwedenEndocrinology and Metabolism Service, Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, IsraelDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, the Hebrew University-Hadassah Medical School, Jerusalem, IsraelDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, the Hebrew University-Hadassah Medical School, Jerusalem, IsraelJerusalem Mental Health Center, Eitanim Psychiatric Hospital, Jerusalem, Israel; Hebrew University-Hadassah School of Medicine, Jerusalem, IsraelSchizophrenia 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.https://elifesciences.org/articles/76391DNA methylationcfDNApsychosisliquid biopsyepigeneticsbiomarker |
| spellingShingle | Asael Lubotzky Ilana Pelov Ronen Teplitz Daniel Neiman Adama Smadja Hai Zemmour Sheina Piyanzin Bracha-Lea Ochana Kirsty L Spalding Benjamin Glaser Ruth Shemer Yuval Dor Yoav Kohn Elevated brain-derived cell-free DNA among patients with first psychotic episode – a proof-of-concept study eLife DNA methylation cfDNA psychosis liquid biopsy epigenetics biomarker |
| 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 | DNA methylation cfDNA psychosis liquid biopsy epigenetics biomarker |
| url | https://elifesciences.org/articles/76391 |
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