We observed altered purine metabolism in MDD patients compared with non-depressed controls. Furthermore, our observations suggest that circulating xanthine may accumulate in MDD patients.

Arginine bioavailability may be decreased in MDD. This could impair the production of nitric oxide, and thus add to oxidative stress in the central nervous system.

Ornithine levels are elevated in general population subjects with persistent pain.

IntroductionTranscranial direct current stimulation (tDCS) is a promising neuromodulation method that has, for example, been used to treat depression. Nevertheless, the adverse effects of tDCS and the validity of the current standard tDCS sham protocols have received limited attention.ObjectivesTo evaluate the extent and types of tDCS adverse effects and to assess the reliability of sham stimulation as a control procedure for tDCS in a double-blind setting.AimsTo compare adverse effects between tDCS and sham stimulation groups, and to determine how well the participants and the experimenter are able to distinguish tDCS from sham stimulation.MethodsA sample of healthy volunteers received a 20-minute session of either tDCS (n = 41; 2 mA) or sham stimulation (n = 41; ramp up 15 s, ramp down 15 s; no current in between). The anode was placed over F3 and cathode over F4. Both the participants and the experimenter reported immediate adverse effects and the perceived likelihood for the participant to receive tDCS. Analyses were conducted using the Mann–Whitney U-test.ResultsThe tDCS group reported more erythema compared with the sham group (P = 0.016, Cohen's D = 0.444). No other significant differences in adverse effects were observed. In the tDCS group, both the participants (P = 0.034, Cohen's D = 0.612) and the experimenter (P = 0.006, Cohen's D = 0.674) reported a higher perceived likelihood of the participant receiving tDCS than in the sham group.ConclusionstDCS has only modest adverse effects. Nevertheless, the current standard sham protocol appears insufficient.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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