Plasma circulating cell-free mitochondrial DNA in depressive disorders

Area of Science:

• Neuroscience
• Immunology
• Biochemistry

Background:

• Plasma cell-free mitochondrial DNA (ccf-mtDNA) is an immunogenic molecule with potential as a biomarker for psychiatric disorders.
• Previous research on ccf-mtDNA levels in depression has yielded inconsistent results, possibly due to small sample sizes and variations in medication status and comorbidities.

Purpose of the Study:

• To investigate plasma ccf-mtDNA levels in a cohort of patients with depressive disorders compared to healthy controls.
• To explore the association between ccf-mtDNA levels and depressive episode status, inflammatory symptoms, and psychotropic medication use.

Main Methods:

• Plasma ccf-mtDNA was measured in 281 patients with depressive disorders and 49 healthy controls.
• Analyses were adjusted for age and sex; patient data included information on medication, personality disorders, and bipolar disorder.
• Statistical analyses included ANOVA and correlation tests to compare groups and assess relationships.

Main Results:

• Significantly different mean plasma ccf-mtDNA levels were observed across current depressive episode, remitted depressive episode, and healthy control groups (F=8.3, p<0.001).
• Both current (p<0.001) and remitted (p=0.002) depression groups exhibited lower ccf-mtDNA levels compared to controls.
• A positive correlation was found between ccf-mtDNA and "inflammatory depression symptoms" (r=0.15, p=0.02) within the depressed group. Treatment with mood stabilizers (lamotrigine, valproic acid, lithium) was associated with lower ccf-mtDNA (F=8.1, p=0.005).

Conclusions:

• Decreased plasma ccf-mtDNA in depression, particularly in difficult-to-treat cases, may be influenced by psychotropic medications and comorbidities.
• The findings suggest that ccf-mtDNA regulation might differ across depression subtypes, warranting further investigation.