Increased 8-hydroxy-deoxyguanosine, a marker of oxidative damage to DNA, in major depression and myalgic encephalomyelitis / chronic fatigue syndrome.
BACKGROUND
There is now evidence that major depression and myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) are accompanied by partially overlapping pathophysiological mechanisms, i.e. activation of various inflammatory and oxidative & nitrosative (IO&NS) pathways.


OBJECTIVE
The aim of the present study was to examine the urinary excretion of 8-hydroxy-deoxyguanosine (8-OhdG), a marker of oxidative damage to DNA, in depression; ME/CFS; and depression and ME/CFS.


METHODS
Toward this end, morning urine was sampled for the assays of 8-OHdG and creatinine, in 44 patients with ME/CFS; 25 with major depression; 23 with depression and ME/CFS; and 17 normal controls. Severity of fatigue and somatic symptoms was measured by means of the Fibromyalgia and CFS Rating (FF) scale.


RESULTS
We found that 49.0% of the variance in the urinary excretion of 8-OHdG was predicted by the regression on creatinine. Consequently, the urinary 8-OHdG excretion should be expressed as the residualized 8-OHdG values after partialling out the effects of creatinine and not by computing the 8-OHdG / creatinine ratio. We found that the residualized urinary excretion of 8-OHdG (adjusted for creatinine) was significantly higher in patients with depression and ME/CFS than in normal controls and all other patients. In the patient group, there were significant correlations between the urinary 8-OHdG and the total score on the FF scale and sadness and flu-like malaise.


CONCLUSIONS
The findings show increased oxidatively generated DNA damage in patients with major depression and ME/CFS and, therefore, further extent the role played by IO&NS pathways in the pathophysiology of both disorders. Since oxidatively damage to DNA is a risk factor for atherosclerosis and neurodegeneration, our results also explain previous findings on increased cardiovascular morbidity in depression and ME/CFS, and neurodegenerative processes in depression.
Maes
Michael
M
Maes Clinics, Wilrijk - Antwerp, Belgium. crc.mh@telenet.be
Mihaylova
Ivanka
I
Kubera
Marta
M
Uytterhoeven
Marc
M
Vrydags
Nicolas
N
Bosmans
Eugene
E
D000080242:8-Hydroxy-2'-Deoxyguanosine / Q000031:analogs & derivatives; D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000652:urine*; D002318:Cardiovascular Diseases / Q000453:epidemiology; D003404:Creatinine / Q000652:urine; D004249:DNA Damage / Q000502:physiology*; D003865:Major Depressive Disorder / Q000453:epidemiology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D015673:Fatigue Syndrome, Chronic / Q000453:epidemiology / Q000378:metabolism*; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000097:blood / Q000652:urine; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009017:Morbidity; D018384:Oxidative Stress / Q000502:physiology; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012307:Risk Factors; D012720:Severity of Illness Index
D015415:Biomarkers; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D006147:Guanine; C078307:8-oxo-7,8-dihydrodeoxyguanine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003404:Creatinine