Plasma circulating free DNA in chronic schizophrenia: a case-control study

Circulating cell-free DNA (cf-DNA) reflects ongoing cell injury and inflammation, but its role in schizophrenia remains unclear. We conducted a case-control study of 33 clinically stabilized patients with chronic schizophrenia and 30 healthy volunteers. Plasma cf-DNA was quantified by fluorometry and droplet digital PCR (ddPCR) targeting nuclear (cf-nucDNA) and mitochondrial (cf-mtDNA) genomes. In unadjusted analyses, patients showed higher cf-nucDNA than controls (p = 0.020), while cf-mtDNA did not differ. After adjusting for age, sex, and smoking, the case-control difference was no longer significant; however, this result should be interpreted with caution due to substantial confounding between disease status, male sex, and smoking habits within our cohort. No associations were found between cf-DNA and symptom severity, despite a predominance of negative symptoms in the study group. These findings suggest that the observed variance in cf-DNA levels is heavily influenced by demographic and lifestyle factors, which complicates the isolation of a distinct disease-specific biological signal in this study group. While ddPCR is a sensitive tool for psychiatric research, current results do not support the routine clinical application of cf-DNA as a biomarker.