PARP1 and OGG1 in medicated patients with depression and the response to ECT.

BACKGROUND
Oxidative stress and oxidation-induced DNA damage may contribute to the pathophysiology of depression. Two key mediators of base excision repair (BER) in response to oxidative damage of DNA are OGG1 and PARP1. Few studies have examined changes in OGG1 or PARP1 mRNA in patients with depression or following antidepressant treatment. We examined PARP1 and OGG1 mRNA levels in patients with depression at baseline/pre-ECT versus in healthy controls and in patients following a course of ECT.


METHODS
PARP1 and OGG1 were examined in whole blood samples from medicated patients with depression and controls using quantitative real-time polymerase chain reaction. Exploratory subgroup correlational analyses were performed to determine associations between PARP1 and OGG1 and mood (HAM-D24) scores as well as with vitamin B3, SIRT1, PGC1α, and TNF-α levels, previously reported on in this cohort.


RESULTS
PARP1 levels were reduced in samples from patients with depression versus controls (p = 0.03), though no difference was noted in OGG1. ECT had no effect on PARP1 or OGG1. Higher baseline PARP1 weakly correlated with greater mood improvement post-ECT (p = 0.008). Moreover, PARP1 positively correlated with SIRT1 at baseline and post-ECT, and positive correlations were noted between change in PARP1 and change in OGG1 with change in TNF-α post-ECT.


CONCLUSIONS
To our knowledge, this is the first study to examine the effect of ECT on BER enzymes. A better understanding of BER enzymes and DNA repair in depression could unearth new mechanisms relevant to the pathophysiology of this condition and novel antidepressant treatments.