Increased oxidation of RNA despite reduced mitochondrial respiration after chronic electroconvulsive stimulation of rat brain tissue.

Major depressive disorder (MDD) affects 350 million people worldwide and is a serious socio-economic burden. The most efficient treatment of MDD is electroconvulsive therapy (ECT), which has been shown to influence the oxidative status believed to be part of the pathophysiology of MDD. We investigated the effects of chronic electroconvulsive stimulation (ECS) on mitochondrial respiration and mitochondrial hydrogen peroxide production, RNA oxidation, and the content of mitochondria in the piriform cortex of the rat. We found reductions of mitochondrial respiration in respiratory states 2 and 3 by 33% and 32%, respectively, and a 23% reduction in electron transfer capacity. RNA oxidation, as measured by 8-oxo-7,8-dihydroguanosine, was increased by 58%, while mitochondrial production of H2O2 was unaffected. The increased oxidative stress may thus be ascribed to extra-mitochondrial sources.

Effects of erythropoietin on depressive symptoms and neurocognitive deficits in depression and bipolar disorder.

BACKGROUND: Depression and bipolar disorder are associated with reduced neural plasticity and deficits in memory, attention and executive function. Drug treatments for these affective disorders have insufficient clinical effects in a large group and fail to reverse cognitive deficits. There is thus a need for more effective treatments which aid cognitive function. Erythropoietin (Epo) is involved in neuroplasticity and is a candidate for future treatment of affective disorders. The investigators have demonstrated that a single dose of Epo improves cognitive function and reduces neurocognitive processing of negative emotional information in healthy and depressed individuals similar to effects seen with conventional antidepressants. The current study adds to the previous findings by investigating whether repeated Epo administration has antidepressant effects in patients with treatment resistant depression and reverses cognitive impairments in these patients and in patients with bipolar disorder in remission. METHODS/DESIGN: The trial has a double-blind, placebo-controlled, parallel-group design. 40 patients with treatment-resistant major depression and 40 patients with bipolar disorder in remission are recruited and randomised to receive weekly infusions of Epo (Eprex; 40,000 IU) or saline (NaCl 0.9%) for 8 weeks. Randomisation is stratified for age and gender. The primary outcome parameters for the two studies are: depression severity measured with the Hamilton Depression Rating Scale 17 items (HDRS-17) 1 in study 1 and, in study 2, verbal memory measured with the Rey Auditory Verbal Learning Test (RAVLT) 23. With inclusion of 40 patients in each study we obtain 86% power to detect clinically relevant differences between intervention and placebo groups on these primary outcomes. TRIAL REGISTRATION: The trial is approved by the Local Ethics Committee: H-C-2008-092, Danish Medicines Agency: 2612-4020, EudraCT: 2008-04857-14, Danish Data Agency: 2008-41-2711 and ClinicalTrials.gov: NCT 00916552.