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Circulating Cell-Free DNA Levels in Psychiatric Diseases: A Systematic Review and Meta-Analysis

Mark M Melamud1, Valentina N Buneva1,2, Evgeny A Ermakov1,2

  • 1Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia.

International Journal of Molecular Sciences
|February 25, 2023
PubMed

Insights

This meta-analysis found significantly higher cell-free DNA (cfDNA) and cell-free genomic DNA (cf-gDNA) in schizophrenia patients compared to healthy individuals. No changes in cell-free mitochondrial DNA (cf-mtDNA) were observed in bipolar disorder or depressive disorders.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Genetics

Background:

  • Circulating cell-free DNA (cfDNA) levels can indicate various pathological conditions.
  • Existing data on cfDNA in severe psychiatric disorders like schizophrenia, bipolar disorder (BD), and depressive disorders (DDs) is inconsistent.

Approach:

  • A meta-analysis was conducted to compare cfDNA concentrations (total, genomic, and mitochondrial) in patients with schizophrenia, BD, and DDs against healthy controls.
  • Standardized Mean Difference (SMD) was used to estimate effect sizes across eight schizophrenia, four BD, and five DD studies.

Key Points:

  • Schizophrenia patients showed significantly elevated total cfDNA and cf-gDNA levels compared to healthy donors (SMD = 0.61 and 0.6, respectively; p < 0.00001).
  • No significant differences in cf-mtDNA levels were found in patients with BD or DDs compared to healthy individuals.
  • Data limitations necessitate further research, particularly for BD and DDs due to small sample sizes and heterogeneity, and for specific cfDNA types in schizophrenia, BD, and DDs.

Conclusions:

  • This meta-analysis provides initial evidence for increased total cfDNA and cf-gDNA in schizophrenia.
  • No alterations in cf-mtDNA were detected in BD and DDs.
  • Elevated cfDNA in schizophrenia may correlate with chronic systemic inflammation, as cfDNA can initiate inflammatory responses.

Keywords:
DAMPsbipolar disordercf-mtDNAcfDNAinflammationmajor depressive disorderschizophrenia

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