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.

IntroductionThe global arginine bioavailability ratio (GABR) is used to estimate arginine supply. Arginine is precursor to nitric oxide (NO) that has been suggested to play a role in major depressive disorder (MDD). NO also participates in neuronal, inflammatory and cardioprotective functions.ObjectivesTo compare GABR between:– D patients and non-depressed controls;– remitted and non-remitted MDD patients;– baseline and follow-up within remitted and non-remitted MDD groups.AimsTo investigate the role of NO production in MDD.MethodsThe sample comprised 99 MDD patients and 253 non-depressed controls (Beck Depression Inventory scores < 10) aged 20–71 years. Altogether, 78 patients returned for the follow-up; 33 were remitted and 45 non-remitted. GABR was calculated from serum levels of arginine, citrulline and ornithine, which were analysed using ultra-performance liquid chromatography. Differences between the study groups were examined using logistic regression adjusted for age, gender, smoking, alcohol use, physical exercise and glycated haemoglobin. The follow-up regression analyses were adjusted for age, gender and physical exercise.ResultsLowered GABR was associated with belonging to the MDD group (OR 0.13, 95% CI 0.03–0.50). Exclusion of participants using anti-depressants that were associated with measured metabolites did not change the results. Over the follow-up period, the remitted and non-remitted groups both showed an increase in GABR (Z = –.53, P < 0.001 and Z = –3.00, P = 0.003, respectively).ConclusionsDecreased GABR may characterise MDD. This could affect neuronal, immunological and cardioprotective functions of NO.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Introduction: Purine metabolism may be affected in major depressive disorder (MDD). Increased enzymatic activity of the purine cycle has been observed in MDD. In MDD patients, purine metabolite levels also react to sertraline treatment. Objectives: To compare serum purine metabolites between: 1) MDD patients and non-depressed controls; and 2) remitted and non-remitted MDD patients. Aims: To clarify the role of purine metabolism in MDD during active illness and recovery. Methods: The sample comprised 99 MDD patients (DSM-IV, SCID interview) and 318 non-depressed controls (Beck Depression Inventory scores < 10) aged 20-71 years. Altogether, 78 patients returned for the follow-up; 33 were remitted and 45 non-remitted. Nine purine cycle metabolites were analysed using ultra performance liquid chromatography. Serum metabolite differences between the study groups were examined using logistic regression adjusted for age, gender, smoking, alcohol use, physical exercise and B-HbAC1. The follow-up analyses were adjusted for age, gender and physical exercise. Results: The participants' likelihood of belonging to the MDD group increased 1.1-fold for each 1-unit decrease in serum inosine, 3.2-fold for each 1-unit decrease in guanosine levels and 2.2-fold for each 1-unit increase in xanthine levels. The remitted and non-remitted groups displayed no significant metabolite differences, but the remitted group showed a non-significant shift of values towards the values of the nondepressed group. Conclusions: Increased degradation of purines and accumulation of xanthine may characterise MDD. Alterations in purine metabolism appear to only partially change during recovery. Nevertheless, recoveryrelated changes require further investigation in larger samples.

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