Oxidative stress–induced nucleic acid damage linked with psychiatric disorders: JAMA

Denmark: The results of a new study conducted by Anders Jorgensen and colleagues showed that people with mental disorders at all diagnostic levels are associated with elevated nucleic acid damage from oxidative stress (NA-OXS) levels. The findings of this study were published in the Journal of American Medical Association - Psychiatry. 

The significantly increased morbidity and death from somatic causes in people with mental illnesses may be caused by nucleic acid damage from oxidative stress, which is thought to be a molecular process. Thus, this study was carried out to comprehensively acquire and evaluate data on NA-OXS throughout the diagnostic range of mental disorders.

Measurement of any marker of DNA or RNA damage from oxidative stress, adult human study population, and either a (1) cross-sectional design comparing patients with psychiatric disorders (any diagnosis) to a control group or (2) prospective intervention were key inclusion criteria in this meta-analysis. Two writers reviewed the research, and two senior authors read the relevant publications in their entirety and evaluated their suitability. The standards for Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) were followed.

The predetermined hypothesis was that those with mental illnesses had higher NA-OXS levels. The major result was the standardized mean differences (SMDs) in nucleic acid oxidation indicators between patients and controls when compared across diagnostic categories. Analyses were separated into a biological matrix and nucleic acid combinations.

The study highlights:

1. 82 studies included 205 patient versus control group comparisons and a sum of 10,151 patient and 10,532 control observations.

2. Overall, individuals with mental illnesses had greater NA-OXS levels than controls across all matrices and compounds.

3. The pooled impact sizes for urine DNA indicators varied from moderate to extremely big for blood cell DNA markers.

4. Patients with dementia had higher NA-OXS levels, followed by those with psychotic and bipolar illnesses.

5. Sensitivity analyses that excluded low-quality studies had no significant effect on the results.

6. There were too few intervention trials and they were too diverse for meaningful meta-analysis.

In conclusion, the Peers found that NA-OXS may contribute to the somatic morbidity and mortality seen in people with mental illnesses.

Reference: 

Jorgensen, A., Baago, I. B., Rygner, Z., Jorgensen, M. B., Andersen, P. K., Kessing, L. V., & Poulsen, H. E. (2022). Association of Oxidative Stress–Induced Nucleic Acid Damage With Psychiatric Disorders in Adults. In JAMA Psychiatry. American Medical Association (AMA). https://doi.org/10.1001/jamapsychiatry.2022.2066