losartan-potassium and Depressive-Disorder

Erythropoietin (EPO) has been suggested to improve metabolism and also cognition, but human studies are scarce. This randomised controlled trial aimed to investigate whether EPO treatment influences body composition and fat and glycated haemoglobin (HbA1c) and fasting glucose, and whether these changes would be associated with previous observed cognitive benefits of EPO.. In total, 84 non-obese patients with treatment-resistant unipolar depression or bipolar disorder in remission were randomised to 8 weekly EPO (40,000 IU) or saline (NaCl 0.9%) infusions in a double-blind, parallel-group design. Patients underwent dual X-ray absorptiometry scans at baseline and week 14 (6 weeks after treatment completion). Cognitive measures were assessed and fasting levels of cholesterol, lipoprotein fractions, triacylglycerides, glucose and HbA1c were obtained at baseline, week 9 and follow-up week 14.. In total, 79 patients had complete pre- and post-treatment data (EPO: N=40, saline: N=39). EPO had no cumulative effect on body composition and markers of fat metabolism. The EPO-treated group exhibited significantly lower HbA1c levels after 8 weeks treatment [F(1, 80)=8.51, p=0.005], however, 6 weeks after treatment termination a significantly higher fasting glucose levels [F(1, 79)=5.85, p=0.02] and HbA1c levels [F(1, 79)=5.85, p=0.02] were seen. The latter increase in HbA1c was further significantly correlated with a better cognitive outcome on verbal memory (r=0.25, p=0.03).. Repeated EPO infusions had no cumulative effect on body composition in this cohort of patients with affective disorders, however, EPO modulated HbA1c and fasting glucose and this was associated with patients' improvement of verbal memory.

Topics: Adipose Tissue; Adult; Bipolar Disorder; Body Composition; Depressive Disorder; Double-Blind Method; Erythropoietin; Female; Glucose; Glycated Hemoglobin; Humans; Male; Treatment Outcome

Bipolar disorder (BD) and unipolar disorder (UD) are associated with cognitive deficits and abnormal neural activity in a "cognitive control network." There is an increased prevalence of cognitive dysfunction in psychiatric patients' first-degree relatives, which constitutes a risk factor for psychiatric illness onset. However, there is no treatment with enduring pro-cognitive efficacy. We found preliminary evidence for beneficial effects of eight weekly doses of recombinant human erythropoietin (EPO) on cognition in BD in a recent randomized controlled trial (RCT). The present RCT consists of two sub-studies that extend our previous work by investigating important novel aspects: (1) the effects of 12 weekly doses of EPO on cognition in first-degree relatives of patients with BD, UD, or schizophrenia; and (2) the effects of extending the treatment schedule from 8 to 12 weeks in remitted patients with BD or UD; and (3) assessment of early treatment-associated neural activity changes that may predict cognitive improvement.. The trial comprises two parallel sub-studies with randomized, controlled, double-blinded, parallel group designs. First-degree relatives (sub-study 1; n = 52) and partially or fully remitted patients with BD or UD (sub-study 2; n = 52) with objectively verified cognitive dysfunction are randomized to receive weekly high-dose EPO (40,000 IU/mL) or placebo (saline) infusions for 12 weeks. Assessments of cognition and mood are conducted at baseline, after two weeks of treatment, after treatment completion, and at six-month follow-up. Functional magnetic resonance imaging (fMRI) is conducted at baseline and after two weeks of treatment. Psychosocial function is assessed at baseline, after treatment completion and six-month follow-up. The primary outcome is change in a cognitive composite score of attention, verbal memory, and executive functions. Statistical power of ≥ 80% is reached to detect a clinically relevant between-group difference by including 52 first-degree relatives and 52 patients with BD or UD, respectively. Behavioral data are analyzed with an intention-to-treat approach using mixed models. fMRI data are analyzed with the FMRIB Software Library.. If this trial reveals pro-cognitive effects of EPO, this may influence future treatment of mood disorders and/or preventive strategies in at-risk populations. The fMRI analyses may unravel key neurobiological targets for pro-cognitive treatment.. ClinicalTrials.gov , NCT03315897. Registered on 20 October 2017.

Topics: Adolescent; Adult; Aged; Bipolar Disorder; Cognition; Depressive Disorder; Double-Blind Method; Erythropoietin; Executive Function; Family; Humans; Magnetic Resonance Imaging; Middle Aged; Mood Disorders; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic; Recombinant Proteins; Research Design; Sample Size; Young Adult

Erythropoietin (EPO) improves verbal memory and reverses subfield hippocampal volume loss across depression and bipolar disorder (BD). This study aimed to investigate with functional magnetic resonance imaging (fMRI) whether these effects were accompanied by functional changes in memory-relevant neuro-circuits in this cohort.. Eighty-four patients with treatment-resistant unipolar depression who were moderately depressed or BD in remission were randomized to eight weekly EPO (40 000 IU) or saline infusions in a double-blind, parallel-group design. Participants underwent whole-brain fMRI at 3T, mood ratings, and blood tests at baseline and week 14. During fMRI, participants performed a picture encoding task followed by postscan recall.. Sixty-two patients had complete data (EPO: N = 32, saline: N = 30). EPO improved picture recall and increased encoding-related activity in dorsolateral prefrontal cortex (dlPFC) and temporo-parietal regions, but not in hippocampus. Recall correlated with activity in the identified dlPFC and temporo-parietal regions at baseline, and change in recall correlated with activity change in these regions from baseline to follow-up across the entire cohort. The effects of EPO were not correlated with change in mood, red blood cells, blood pressure, or medication.. The findings highlight enhanced encoding-related dlPFC and temporo-parietal activity as key neuronal underpinnings of EPO-associated memory improvement.

Topics: Adult; Depressive Disorder; Depressive Disorder, Treatment-Resistant; Double-Blind Method; Erythropoietin; Female; Humans; Magnetic Resonance Imaging; Male; Mental Recall; Middle Aged; Prefrontal Cortex; Psychiatric Status Rating Scales; Treatment Outcome

Persistent cognitive dysfunction in depression and bipolar disorder (BD) impedes patients' functional recovery. Erythropoietin (EPO) increases neuroplasticity and reduces cognitive difficulties in treatment-resistant depression (TRD) and remitted BD. This magnetic resonance imaging study assessed the neuroanatomical basis for these effects.. Patients with TRD who were moderately depressed or BD in partial remission were randomized to 8 weekly EPO (40,000 IU) or saline infusions in a double-blind, parallel-group design. Patients underwent magnetic resonance imaging, memory assessment with the Rey Auditory Verbal Learning Test, and mood ratings with the Beck Depression Inventory, Hamilton Depression Rating Scale, and Young Mania Rating Scale at baseline and week 14. Hippocampus segmentation and analysis of hippocampal volume, shape, and gray matter density were conducted with FMRIB Software Library tools. Memory change was analyzed with repeated-measures analysis of covariance adjusted for depression symptoms, diagnosis, age, and gender.. Eighty-four patients were randomized; 1 patient withdrew and data collection was incomplete for 14 patients; data were thus analyzed for 69 patients (EPO: n = 35, saline: n = 34). Compared with saline, EPO was associated with mood-independent memory improvement and reversal of brain matter loss in the left hippocampal cornu ammonis 1 to cornu ammonis 3 and subiculum. Using the entire sample, memory improvement was associated with subfield hippocampal volume increase independent of mood change.. EPO-associated memory improvement in TRD and BD may be mediated by reversal of brain matter loss in a subfield of the left hippocampus. EPO may provide a therapeutic option for patients with mood disorders who have impaired neuroplasticity and cognition.

Topics: Adult; Bipolar Disorder; Depressive Disorder; Depressive Disorder, Treatment-Resistant; Erythropoietin; Female; Hippocampus; Humans; Magnetic Resonance Imaging; Male; Memory; Middle Aged; Mood Disorders; Psychiatric Status Rating Scales

Erythropoietin (Epo) has neuroprotective and neurotrophic effects in animal models and affects cognitive and associated neural responses in humans. These effects have highlighted Epo as a candidate for treatment of psychiatric disease including schizophrenia and depression. The current study aimed to explore the effects of Epo on neural and behavioral measures of emotional processing relevant for depression and the effects of conventional antidepressant medication.. In the present study, we used functional magnetic resonance imaging to explore the effects of Epo (40,000 IU) versus saline on the neural processing of happy and fearful faces in 23 healthy volunteers. Facial expression recognition was assessed outside the scanner.. One week after administration, Epo reduced neural response to fearful versus neutral faces in the occipito-parietal cortex consistent with reduced attention to fear. Erythropoietin additionally reduced recognition of fearful facial expressions without affecting recognition of other emotional expressions. These actions occurred in the absence of changes in hematological parameters.. The present study demonstrates that Epo directly modulates brain responses to emotional information in humans in a manner consistent with the actions of conventional antidepressants. The characterization of the effects of Epo in a clinically depressed group is therefore warranted.

Topics: Adolescent; Adult; Affect; Antidepressive Agents; Cognition; Depressive Disorder; Double-Blind Method; Emotions; Erythrocyte Volume; Erythropoietin; Facial Expression; Fear; Female; Humans; Magnetic Resonance Imaging; Male; Occipital Lobe; Oxygen; Parietal Lobe; Photic Stimulation; Recognition, Psychology

As a component of the open-label, multicenter National Cooperative Recombinant Human Erythropoietin (Epo) Study, the health-related quality-of-life effects of Epo therapy were assessed in 484 dialysis patients who had not previously been treated with Epo therapy (New-to-Epo) and 520 dialysis patients who were already receiving Epo therapy at the time of study enrollment (Old-to-Epo). Using scales from the Medical Outcomes Study 36-item Short Form Health Survey (SF-36), health-related quality of life was assessed on study enrollment (baseline) and at an average of 99 days follow-up. At baseline, SF-36 scores for Old- and New-to-Epo patients were well below those observed in the general population, reflecting substantial impairments in functional status and well-being among patients with chronic renal failure. Significant improvements from baseline to follow-up were observed among New-to-Epo patients in vitality, physical functioning, social functioning, mental health, looking after the home, social life, hobbies, and satisfaction with sexual activity (P < 0.05 for each). The mean improvements in hematocrit values among New-to-Epo and Old-to Epo patients were 4.6 and 0.3, respectively. At the time of follow-up, SF-36 scores for New-to-Epo patients were comparable with those observed among Old-to-Epo patients, whose scores did not change significantly from baseline to follow-up. Analysis of the relationship between Epo therapy, hematocrit values, and health-related quality of life suggest that some of the beneficial quality-of-life effects of Epo are mediated through a change in hematocrit level.

Topics: Activities of Daily Living; Adult; Aged; Anemia; Comorbidity; Depressive Disorder; Erythropoietin; Female; Heart Failure; Hematocrit; Humans; Kidney Failure, Chronic; Male; Middle Aged; Patient Acceptance of Health Care; Peritoneal Dialysis; Quality of Life; Racial Groups; Recombinant Proteins; Renal Dialysis; Self-Assessment

New perspectives have emerged regarding the processes associated with depressive disorders and their many comorbid conditions. Particular attention has been paid to the potential role of inflammatory factors in promoting these illnesses. These inflammatory responses include those elicited by pathogenic stimuli, as well as sterile inflammatory processes, such as those related to severe or chronic stress. These diverse challenges may activate common processes in which cytokines, which are inflammatory signaling molecules, provoke the dysregulation of several growth factors, including brain-derived neurotrophic factor, fibroblast growth factor-2, macrophage migration inhibitory factor, and erythropoietin. The result of such dysregulation favors the development of depressive disorders and their comorbid illnesses, such as heart disease, diabetes, autoimmune conditions, and poststroke depression.

Topics: Animals; Brain-Derived Neurotrophic Factor; Comorbidity; Cytokines; Depressive Disorder; Diabetes Mellitus; Erythropoietin; Fibroblast Growth Factor 2; Heart Diseases; Humans; Inflammation Mediators; Interleukin-6; Macrophage Migration-Inhibitory Factors; Models, Biological; Models, Psychological; Signal Transduction; Stress, Psychological; Tumor Necrosis Factor-alpha