Elevated brain-derived cell-free DNA among patients with first psychotic episode - a proof-of-concept study.
Level 4 - case-series / case-control
Case-control proof-of-concept biomarker study
PubMed 35699419 · doi:10.7554/eLife.76391
What was done
Researchers developed a panel of brain-specific DNA methylation markers to identify the tissue origin of cell-free DNA (cfDNA) in peripheral blood. They compared plasma levels of neuron-, astrocyte-, oligodendrocyte-, and whole brain-derived cfDNA between 29 patients experiencing a first psychotic episode and 31 healthy controls, evaluating diagnostic performance and correlations with psychotropic medication use.
What was found
Patients experiencing a first psychotic episode showed significantly elevated levels of neuron-derived (p=0.0013), astrocyte-derived (p=0.0016), oligodendrocyte-derived (p=0.0129), and whole brain-derived (p=0.0012) cfDNA compared to healthy controls. These elevations did not correlate with psychotropic medication use. The biomarker panel yielded an area under the curve (AUC) of 0.77, with 65% sensitivity at 90% specificity.
Why it matters
This study provides proof-of-concept that liquid biopsies detecting brain-specific cfDNA methylation may serve as non-invasive biomarkers to assist in the early detection and monitoring of schizophrenia.
Limits
The sample size was small (29 cases and 31 controls) and cross-sectional. The abstract does not evaluate specificity against other psychiatric or neurological disorders, nor does it establish the precise mechanism driving elevated cfDNA, such as increased cell death, blood-brain barrier permeability, or impaired clearance.
Cited by
- supports Cell-free DNA released from dying brain neurons enters the bloodstream and can be identified as neuron-derived using cell-type-specific epigenetic methylation marks.