losartan-potassium and Depressive-Disorder--Major

The purpose of this study is to systematically review the efficacy and safety of adjunctive erythropoietin (EPO) in treating cognitive deficits associated with schizophrenia, bipolar disorder, and major depression based on randomized controlled trials (RCTs).. Two evaluators independently and systematically searched and selected studies, extracted data, and conducted quality assessment.. Four RCTs with 144 patients (71 in the EPO group and 73 in the placebo group) met the study entry criteria. Adjunctive EPO could improve schizophrenia-related cognitive performance. In patients with bipolar disorder, EPO could also enhance sustained attention, recognition of happy faces, and speed of complex information processing across learning, attention, and executive function when compared with placebo. In addition, EPO could enhance verbal recall, recognition, and memory in patients with major depression.. This preliminary study found that adjunctive EPO appears to be effective in treating cognitive deficits associated with schizophrenia, bipolar disorder, and major depression without major adverse effects observed. Further higher quality RCTs with larger samples are needed to confirm the findings.. CRD42017058094.

Topics: Bipolar Disorder; Cognition Disorders; Depressive Disorder, Major; Erythropoietin; Humans; Randomized Controlled Trials as Topic; Schizophrenia

The 39th Annual meeting of the Society for Neuroscience was held in Chicago, Illinois, USA from 17 to 21 October, 2009. The conference was attended by more than 33,000 delegates from across the globe including scientists from both basic and clinical settings. Co-incidentally, this year, the scientific community is commemorating the 200th anniversary of the birth of the famous English naturalist and biologist, Charles Darwin, who described the theory of natural selection. Keeping its traditions, the congress discussed various new advances in the area of neuroscience. The topics were divided into symposia, mini-symposia, nano-symposia, special lectures and poster sessions. The main areas of discussion were novel discoveries in Alzheimer's, Parkinson's, drug addiction, autism, epilepsy and major depression. According to the WHO, neurological disorders are one of the greatest threats to public health. There are many unknown and challenging facts in the field of neuroscience that needs exploration. It is unfortunate that despite the availability of various drugs for treating these disorders, a sizeable population still do not achieve complete remission. Therefore, organizing such events and addressing the latest developments may open new treatment vistas for patients suffering from these disorders. The present review discusses some of the outcomes of the deliberations in the field of epilepsy and major depression.

Topics: Administration, Inhalation; Adrenergic Uptake Inhibitors; Anti-Inflammatory Agents; Anticonvulsants; Antidepressive Agents; Depressive Disorder, Major; Dopamine Uptake Inhibitors; Epilepsy; Erythropoietin; Glutamates; Humans; Inflammation; Receptors, Cannabinoid; Recombinant Proteins; Selective Serotonin Reuptake Inhibitors; Signal Transduction; Wnt Proteins

Cognitive dysfunction in depression and bipolar disorder (BD) is insufficiently targeted by available treatments. Erythropoietin (EPO) increases neuroplasticity and may improve cognition in mood disorders, but the neuronal mechanisms of these effects are unknown. This functional magnetic resonance imaging (fMRI) study investigated the effects of EPO on neural circuitry activity during working memory (WM) performance.. Patients with treatment-resistant major depression, who were moderately depressed, or with BD in partial remission, were randomized to eight weekly infusions of EPO (40 000 IU) (N = 30) or saline (N = 26) in a double-blind, parallel-group design. Patients underwent fMRI, mood ratings and blood tests at baseline and week 14. During fMRI patients performed an n-back WM task.. EPO improved WM accuracy compared with saline (p = 0.045). Whole-brain analyses revealed that EPO increased WM load-related activity in the right superior frontal gyrus (SFG) compared with saline (p = 0.01). There was also enhanced WM load-related deactivation of the left hippocampus in EPO-treated compared to saline-treated patients (p = 0.03). Across the entire sample, baseline to follow-up changes in WM performance correlated positively with changes in WM-related SFG activity and negatively with hippocampal response (r = 0.28-0.30, p < 0.05). The effects of EPO were not associated with changes in mood or red blood cells (p ⩾0.08).. The present findings associate changes in WM-load related activity in the right SFG and left hippocampus with improved executive function in EPO-treated patients.. clinicaltrials.gov: NCT00916552.

Topics: Adult; Bipolar Disorder; Brain; Cognitive Dysfunction; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Double-Blind Method; Erythropoietin; Executive Function; Female; Functional Neuroimaging; Humans; Magnetic Resonance Imaging; Male; Memory, Short-Term; Middle Aged; Spatial Memory; Treatment Outcome

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.. 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.. 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.

Topics: Affect; Antidepressive Agents; Attention; Bipolar Disorder; Clinical Protocols; Cognition; Denmark; Depressive Disorder, Major; Double-Blind Method; Erythropoietin; Executive Function; Humans; Memory; Neuronal Plasticity; Neuropsychological Tests; Placebo Effect; Psychiatric Status Rating Scales; Research Design; Surveys and Questionnaires; Time Factors; Treatment Outcome

Erythropoietin (Epo) has neurotrophic effects and may be a novel therapeutic agent in the treatment of depression. We have found antidepressant-like effects of Epo on emotional processing and mood in healthy volunteers.. The current study aimed to explore the effects of Epo on the neural processing of emotional information in depressed patients.. Seventeen patients with acute major depressive disorder were randomised to receive Epo (40,000 IU) or saline iv in a double-blind, parallel-group design. On day 3, we assessed neural responses to positive, negative and neutral pictures during fMRI followed by picture recall after the scan. Mood and blood parameters were assessed at baseline and on day 3.. Epo reduced neural response to negative vs. positive pictures 3 days post-administration in a network of areas including the hippocampus, ventromedial prefrontal and parietal cortex. After the scan, Epo-treated patients showed improved memory compared with those that were given placebo. The effects occurred in the absence of changes in mood or haematological parameters, suggesting that they originated from direct neurobiological actions of Epo.. These findings are similar to the effects of conventional antidepressants and opposite to the negative biases in depression. The central effects of Epo therefore deserve further investigation as a potential antidepressant mechanism.

Topics: Adult; Antidepressive Agents; Bias; Brain; Brain Mapping; Depressive Disorder, Major; Double-Blind Method; Emotions; Erythropoietin; Facial Expression; Female; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Oxygen; Photic Stimulation; Reaction Time; Recognition, Psychology; Time Factors; Young Adult

Major depressive disorder (MDD) is the most common psychiatric disease worldwide. The precise molecular and cellular mechanisms underlying this disorder remain largely unknown. Wilms' tumor 1 (Wt1), a transcription factor, plays critical roles in cancer and organ development. Importantly, deletion of the 11p13 region that contains the WT1 gene is a major cause of WARG syndrome (Wilms' tumor, aniridia, genitourinary anomalies, and mental retardation), which is characterized by psychiatric disease, including depression. However, the roles and mechanisms of WT1 in embryonic neurogenesis and psychiatric disease remain unclear. Here, we demonstrate that the brain-specific deletion of Wt1 results in abnormal cell distribution during embryonic neurogenesis, which is accompanied by enhanced proliferation of neural progenitors and reduced neuronal differentiation. Moreover, neurons exhibit abnormal morphology during cortical development following Wt1 ablation. Furthermore, Wt1

Topics: Animals; Brain; Depressive Disorder, Major; Dioxygenases; DNA-Binding Proteins; Erythropoietin; Gene Deletion; Mice; WT1 Proteins

It is hypothesized that major depression disorder (MDD) is associated with impaired neuronal plasticity, and that antidepressant treatments restore neuroplasticity. Brain-derived neurotrophic factor (BDNF) and erythropoietin (Epo) show neurotrophic and neuroprotective effects. We evaluated plasma Epo and BDNF levels in 50 MDD inpatients before treatment and in 50 healthy controls. The MDD inpatients consisted of 20 MDD patients without and 30 MDD patients with a recent suicide attempt. The plasma Epo level was significantly higher in nonsuicidal and suicidal MDD patients than in healthy controls (p ≤ 0.001), while the plasma BDNF level was significantly lower in suicidal MDD than in nonsuicidal MDD patients and healthy controls (p ≤ 0.001). When classifying study participants into low-Epo and high-Epo and low-BDNF and high-BDNF subgroups based on the cutoff of Epo or BDNF calculated using receiver operating characteristics (ROC) curve analysis, logistic regression analysis revealed that high-Epo and low-BDNF status correlated with a respective significant odds ratio of 7.367 (p = 0.015) and 33.123 (p ≤ 0.001) for suicidal MDD. In conclusion, plasma BDNF level was decreased in untreated MDD patients, which was presumed to be a dysfunctional effect of the onset of MDD. However, an increase in plasma Epo was observed in MDD in connection with a recent suicide attempt, indicating that this triggers hypoxic stress to induce a compensatory increase in Epo.

Topics: Adult; Biomarkers; Brain-Derived Neurotrophic Factor; Depressive Disorder, Major; Erythropoietin; Female; Humans; Male; Middle Aged; Suicide, Attempted

Topics: Animals; Brain-Derived Neurotrophic Factor; Depressive Disorder, Major; Erythropoietin; Humans; Nerve Growth Factors; Neuronal Plasticity