55 research outputs found
Effects of erythropoietin on depressive symptoms and neurocognitive deficits in depression and bipolar disorder
<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods/design</p> <p>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) <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> in study 1 and, in study 2, verbal memory measured with the Rey Auditory Verbal Learning Test (RAVLT) <abbrgrp><abbr bid="B2">2</abbr><abbr bid="B3">3</abbr></abbrgrp>. 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.</p> <p>Trial registration</p> <p>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.</p
Haemoglobin mass and running time trial performance after recombinant human erythropoietin administration in trained men
<p>Recombinant human erythropoietin (rHuEpo) increases haemoglobin mass (Hbmass) and maximal oxygen uptake (v˙ O2 max).</p>
<p>Purpose: This study defined the time course of changes in Hbmass, v˙ O2 max as well as running time trial performance
following 4 weeks of rHuEpo administration to determine whether the laboratory observations would translate into actual
improvements in running performance in the field.</p>
<p>Methods: 19 trained men received rHuEpo injections of 50 IUNkg21 body mass every two days for 4 weeks. Hbmass was
determined weekly using the optimized carbon monoxide rebreathing method until 4 weeks after administration. v˙ O2 max
and 3,000 m time trial performance were measured pre, post administration and at the end of the study.</p>
<p>Results: Relative to baseline, running performance significantly improved by ,6% after administration (10:3061:07 min:sec
vs. 11:0861:15 min:sec, p,0.001) and remained significantly enhanced by ,3% 4 weeks after administration
(10:4661:13 min:sec, p,0.001), while v˙ O2 max was also significantly increased post administration
(60.765.8 mLNmin21Nkg21 vs. 56.066.2 mLNmin21Nkg21, p,0.001) and remained significantly increased 4 weeks after
rHuEpo (58.065.6 mLNmin21Nkg21, p = 0.021). Hbmass was significantly increased at the end of administration compared to
baseline (15.261.5 gNkg21 vs. 12.761.2 gNkg21, p,0.001). The rate of decrease in Hbmass toward baseline values post
rHuEpo was similar to that of the increase during administration (20.53 gNkg21Nwk21, 95% confidence interval (CI) (20.68,
20.38) vs. 0.54 gNkg21Nwk21, CI (0.46, 0.63)) but Hbmass was still significantly elevated 4 weeks after administration
compared to baseline (13.761.1 gNkg21, p<0.001).</p>
<p>Conclusion: Running performance was improved following 4 weeks of rHuEpo and remained elevated 4 weeks after
administration compared to baseline. These field performance effects coincided with rHuEpo-induced elevated v˙ O2 max and
Hbmass.</p>
Methodological recommendations for cognition trials in bipolar disorder by the International Society for Bipolar Disorders Targeting Cognition Task Force
Effects of the 5-HT2C receptor agonist meta-chlorophenylpiperazine on appetite, food intake and emotional processing in healthy volunteers
RATIONALE: The treatment of obesity is an increasing global health priority, yet few effective drug treatments are currently available. The discovery of novel anti-obesity therapies could be assisted by the validation of experimental (translational) medicine models in healthy volunteers that assess efficacy and safety at an early stage of drug development. OBJECTIVES: The aim of this study was to examine the effects of the 5-HT2C receptor agonist meta-chlorophenylpiperazine (mCPP) in an experimental medicine model assessing both appetite and mood. METHODS: Using a between-subjects, double-blind, placebo-controlled design, 24 male and 24 female participants were randomly assigned to either placebo, 15- or 30-mg mCPP treatment groups. Lunch was eaten from a Universal Eating Monitor (UEM) that measured eating rate, and the participants completed the P1vital® Oxford Emotional Test Battery (ETB) and a series of appetite and mood ratings. RESULTS: mCPP reduced appetite and, in women, enhanced measures of satiation. The drug also enhanced memory for emotional material in the word recall and recognition memory tasks of the ETB. CONCLUSIONS: The results provide new insight into the effects of mCPP on appetite, satiety and memory in humans. In addition, our data provide an illustration of the value of measuring changes in appetite and mood in healthy volunteers to determine the potential efficacy and safety of novel anti-obesity drugs
Erythropoietin: a multimodal neuroprotective agent
The tissue protective functions of the hematopoietic growth factor erythropoietin (EPO) are independent of its action on erythropoiesis. EPO and its receptors (EPOR) are expressed in multiple brain cells during brain development and upregulated in the adult brain after injury. Peripherally administered EPO crosses the blood-brain barrier and activates in the brain anti-apoptotic, anti-oxidant and anti-inflammatory signaling in neurons, glial and cerebrovascular endothelial cells and stimulates angiogenesis and neurogenesis. These mechanisms underlie its potent tissue protective effects in experimental models of stroke, cerebral hemorrhage, traumatic brain injury, neuroinflammatory and neurodegenerative disease. The preclinical data in support of the use of EPO in brain disease have already been translated to first clinical pilot studies with encouraging results with the use of EPO as a neuroprotective agent
Evaluating endophenotypes for bipolar disorder
Background: Phenotypic heterogeneity is a major impediment to the elucidation of the neurobiology and genetics of bipolar disorder. Endophenotype could help in reducing heterogeneity by defining biological traits that are more direct expressions of gene effects. The aim of this review is to examine the recent literature on clinical, epidemiological, neurobiological, and genetic findings and to select and evaluate candidate endophenotypes for bipolar disorder. Evaluating putative endophenotype could be helpful in better understanding the neurobiology of bipolar disorder by improving the definition of bipolar-related phenotypes in genetic studies. In this manner, research on endophenotypes could be useful to improve psychopathological diagnostics in the long-run by dissecting psychiatric macro phenotypes into biologically valid components. Main body: The associations among the psychopathological and biological endophenotypes are discussed with respect to specificity, temporal stability, heritability, familiarity, and clinical and biological plausibility. Numerous findings regarding brain function, brain structure, neuropsychology and altered neurochemical pathways in patients with bipolar disorder and their relatives deserve further investigation. Overall, major findings suggest a developmental origin of this disorder as all the candidate endophenotypes that we have been able to select are present both in the early stages of the disorder as well as in subjects at risk. Conclusions: Among the stronger candidate endophenotypes, we suggest circadian rhythm instability, dysmodulation of emotion and reward, altered neuroimmune state, attention and executive dysfunctions, anterior cingulate cortex thickness and early white matter abnormalities. In particular, early white matter abnormalities could be the result of a vulnerable brain on which new stressors are added in young adulthood which favours the onset of the disorder. Possible pathways that lead to a vulnerable brain are discussed starting from the data about molecular and imaging endophenotypes of bipolar disorder
Systematic review of randomized controlled trials of candidate treatments for cognitive impairment in depression and methodological challenges in the field
Effects of psychological and pharmacological interventions on anxiety symptoms in patients with bipolar disorder in full or partial remission:A systematic review
Recombinant Human Erythropoietin for Treating Treatment-Resistant Depression: A Double-Blind, Randomized, Placebo-Controlled Phase 2 Trial
Assessment of the neuronal underpinnings of cognitive impairment in bipolar disorder with a picture encoding paradigm and methodological lessons learnt
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