Circulating Cell-Free DNA Levels in Psychiatric Diseases: A Systematic Review and Meta-Analysis
The cell-free DNA (cfDNA) levels are known to increase in biological fluids in various pathological conditions. However, the data on circulating cfDNA in severe psychiatric disorders, including schizophrenia, bipolar disorder (BD), and depressive disorders (DDs), is contradictory. This meta-analysis...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-02-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/4/3402 |
| _version_ | 1797620568980193280 |
|---|---|
| author | Mark M. Melamud Valentina N. Buneva Evgeny A. Ermakov |
| author_facet | Mark M. Melamud Valentina N. Buneva Evgeny A. Ermakov |
| author_sort | Mark M. Melamud |
| collection | DOAJ |
| description | The cell-free DNA (cfDNA) levels are known to increase in biological fluids in various pathological conditions. However, the data on circulating cfDNA in severe psychiatric disorders, including schizophrenia, bipolar disorder (BD), and depressive disorders (DDs), is contradictory. This meta-analysis aimed to analyze the concentrations of different cfDNA types in schizophrenia, BD, and DDs compared with healthy donors. The mitochondrial (cf-mtDNA), genomic (cf-gDNA), and total cfDNA concentrations were analyzed separately. The effect size was estimated using the standardized mean difference (SMD). Eight reports for schizophrenia, four for BD, and five for DDs were included in the meta-analysis. However, there were only enough data to analyze the total cfDNA and cf-gDNA in schizophrenia and cf-mtDNA in BD and DDs. It has been shown that the levels of total cfDNA and cf-gDNA in patients with schizophrenia are significantly higher than in healthy donors (SMD values of 0.61 and 0.6, respectively; <i>p</i> < 0.00001). Conversely, the levels of cf-mtDNA in BD and DDs do not differ compared with healthy individuals. Nevertheless, further research is needed in the case of BD and DDs due to the small sample sizes in the BD studies and the significant data heterogeneity in the DD studies. Additionally, further studies are needed on cf-mtDNA in schizophrenia or cf-gDNA and total cfDNA in BD and DDs due to insufficient data. In conclusion, this meta-analysis provides the first evidence of increases in total cfDNA and cf-gDNA in schizophrenia but shows no changes in cf-mtDNA in BD and DDs. Increased circulating cfDNA in schizophrenia may be associated with chronic systemic inflammation, as cfDNA has been found to trigger inflammatory responses. |
| first_indexed | 2024-03-11T08:43:26Z |
| format | Article |
| id | doaj.art-deb99090e3dd425cb173e7aedc32fa9a |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T08:43:26Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-deb99090e3dd425cb173e7aedc32fa9a2023-11-16T20:59:27ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01244340210.3390/ijms24043402Circulating Cell-Free DNA Levels in Psychiatric Diseases: A Systematic Review and Meta-AnalysisMark M. Melamud0Valentina N. Buneva1Evgeny A. Ermakov2Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, RussiaThe cell-free DNA (cfDNA) levels are known to increase in biological fluids in various pathological conditions. However, the data on circulating cfDNA in severe psychiatric disorders, including schizophrenia, bipolar disorder (BD), and depressive disorders (DDs), is contradictory. This meta-analysis aimed to analyze the concentrations of different cfDNA types in schizophrenia, BD, and DDs compared with healthy donors. The mitochondrial (cf-mtDNA), genomic (cf-gDNA), and total cfDNA concentrations were analyzed separately. The effect size was estimated using the standardized mean difference (SMD). Eight reports for schizophrenia, four for BD, and five for DDs were included in the meta-analysis. However, there were only enough data to analyze the total cfDNA and cf-gDNA in schizophrenia and cf-mtDNA in BD and DDs. It has been shown that the levels of total cfDNA and cf-gDNA in patients with schizophrenia are significantly higher than in healthy donors (SMD values of 0.61 and 0.6, respectively; <i>p</i> < 0.00001). Conversely, the levels of cf-mtDNA in BD and DDs do not differ compared with healthy individuals. Nevertheless, further research is needed in the case of BD and DDs due to the small sample sizes in the BD studies and the significant data heterogeneity in the DD studies. Additionally, further studies are needed on cf-mtDNA in schizophrenia or cf-gDNA and total cfDNA in BD and DDs due to insufficient data. In conclusion, this meta-analysis provides the first evidence of increases in total cfDNA and cf-gDNA in schizophrenia but shows no changes in cf-mtDNA in BD and DDs. Increased circulating cfDNA in schizophrenia may be associated with chronic systemic inflammation, as cfDNA has been found to trigger inflammatory responses.https://www.mdpi.com/1422-0067/24/4/3402cfDNAcf-mtDNADAMPsschizophreniabipolar disordermajor depressive disorder |
| spellingShingle | Mark M. Melamud Valentina N. Buneva Evgeny A. Ermakov Circulating Cell-Free DNA Levels in Psychiatric Diseases: A Systematic Review and Meta-Analysis International Journal of Molecular Sciences cfDNA cf-mtDNA DAMPs schizophrenia bipolar disorder major depressive disorder |
| title | Circulating Cell-Free DNA Levels in Psychiatric Diseases: A Systematic Review and Meta-Analysis |
| title_full | Circulating Cell-Free DNA Levels in Psychiatric Diseases: A Systematic Review and Meta-Analysis |
| title_fullStr | Circulating Cell-Free DNA Levels in Psychiatric Diseases: A Systematic Review and Meta-Analysis |
| title_full_unstemmed | Circulating Cell-Free DNA Levels in Psychiatric Diseases: A Systematic Review and Meta-Analysis |
| title_short | Circulating Cell-Free DNA Levels in Psychiatric Diseases: A Systematic Review and Meta-Analysis |
| title_sort | circulating cell free dna levels in psychiatric diseases a systematic review and meta analysis |
| topic | cfDNA cf-mtDNA DAMPs schizophrenia bipolar disorder major depressive disorder |
| url | https://www.mdpi.com/1422-0067/24/4/3402 |
| work_keys_str_mv | AT markmmelamud circulatingcellfreednalevelsinpsychiatricdiseasesasystematicreviewandmetaanalysis AT valentinanbuneva circulatingcellfreednalevelsinpsychiatricdiseasesasystematicreviewandmetaanalysis AT evgenyaermakov circulatingcellfreednalevelsinpsychiatricdiseasesasystematicreviewandmetaanalysis |