olanzapine and Cognitive-Dysfunction

Schizophrenia patients show executive function (EF) impairments in voluntary orienting as measured by eye-movements. We tested 14 inpatients to investigate the effects of the antipsychotic olanzapine on EF, as measured by antisaccade eye-movement performance.. Patients were tested at baseline (before olanzapine), 3-5 days post-medication, and 12-14 days post-medication. Patients were also assessed on the Positive and Negative Syndrome Scale (PANSS) to measure the severity of schizophrenia-related symptoms, and administered the Stroop task, a test of EF. Nine matched controls were also tested on the antisaccade and Stroop.. Both groups showed improvement on Stroop and antisaccade; however, the schizophrenia group improved significantly more on antisaccade, indicating an additional benefit of olanzapine on EF performance. Patients with poorer baseline antisaccade performance (High-Deficit) showed significantly greater improvement on the antisaccade task than patients with better baseline performance (Low-Deficit), suggesting that baseline EF impairment predicts the magnitude of cognitive improvement with olanzapine. These subgroups showed significant and equivalent improvement on PANSS scores, indicating that improvement on the antisaccade task with olanzapine was not a result of differences in magnitude of clinical improvement.. This preliminary study provides evidence that olanzapine may be most advantageous for patients with greater baseline EF deficits.

Topics: Adolescent; Adult; Antipsychotic Agents; Cognitive Dysfunction; Executive Function; Eye Movements; Female; Humans; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Stroop Test; Treatment Outcome; Young Adult

Our previous study showed that metabolic abnormalities reduced the levels of brain-derived neurotrophic factor (BDNF) and deteriorated cognitive performance in patients with schizophrenia. Inflammation may play a key role in this process. Omega-3 fatty acids have been documented to ameliorate inflammation. Therefore, we hypothesized that omega-3 fatty acids may be of value in enhancing BDNF levels and improving cognitive function in patients with schizophrenia with metabolic syndrome (MetS). We recruited 80 patients with both schizophrenia and MetS who received long-term olanzapine monotherapy. The enzyme-linked immunosorbent assay was used to measure the plasma levels of C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). The patients were randomly assigned to the OMG-3 group (n = 40) or the placebo group (n = 40). Of the 80 patients who consented to the study, 72 completed this 12-week RCT. The primary outcome was the changes from baseline to 12 weeks in clinical characteristics and the levels of BDNF, CRP, IL-6 and TNF-α. There was a significant correlation between omega-3 fatty acid treatment and enhanced delayed memory factor in the RBANS assessment (F

Topics: Cognitive Dysfunction; Fatty Acids, Omega-3; Humans; Metabolic Syndrome; Olanzapine; Schizophrenia

The selective activation of the muscarinic M

Topics: Allosteric Regulation; Animals; Antipsychotic Agents; CHO Cells; Cognition; Cognitive Dysfunction; Cricetulus; Disease Models, Animal; Haloperidol; Humans; Memory, Short-Term; Mice; Mice, Transgenic; MicroRNAs; Muscarinic Agonists; Olanzapine; Quetiapine Fumarate; Receptor, Muscarinic M1; Recombinant Proteins; Schizophrenia; Social Behavior

Schizophrenia is a chronic, disabling neurological illness. This study investigated the effect of rosuvastatin (RSU) addition to the antipsychotic drug: olanzapine (OLZ) in treatment of post-weaning isolation rearing (IR) damaging effect and assessed behavioral impairment, metabolic and hepatic abnormalities, oxidative stress, and inflammatory markers.. Treatment with OLZ (6 mg/kg, P.O.) and/or RSU (10 mg/kg, I.P.) have been started 6 weeks after isolation. We assessed behavioral tests, serum cortisol level, and hippocampal content of neurotransmitters. In addition, we assessed histopathology, inflammatory and oxidative stress markers of hippocampus, liver and adipose tissue RESULTS: Treatment of IR animals with OLZ, and/or RSU significantly counteracted the changes in hippocampus, liver and adipose tissue induced by post-weaning IR. Co-treatment of IR rats with both OLZ and RSU showed additive effects in some areas like improving both tumor necrosis factor alpha (TNFα) in both hippocampus and liver, histopathology of liver, oxidative stress markers of adipose tissue, β. post-weaning IR as a model has behavioral, hippocampal, hepatic and marked metabolic changes more relevant to schizophrenia than drug-induced models. These effects were ameliorated by RSU and/or OLZ that are explained by their antioxidant, anti-inflammatory, anti-stress and anti-hyperlipidemic properties. Interestingly, co-treatment with both drugs showed a better effect.

Topics: Animals; Antipsychotic Agents; Cognitive Dysfunction; Disease Models, Animal; Drug Therapy, Combination; Hippocampus; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Liver Diseases; Male; Olanzapine; Oxidative Stress; Rats; Rats, Sprague-Dawley; Rosuvastatin Calcium; Schizophrenia; Social Isolation; Tumor Necrosis Factor-alpha

A new strategy in the design of aminergic GPCR ligands is proposed - the use of aromatic, heterocyclic basic moieties in place of the evergreen piperazine or alicyclic and aliphatic amines. This hypothesis has been tested using a benchmark series of 5-HT

Topics: Animals; Cells, Cultured; Cognitive Dysfunction; Dose-Response Relationship, Drug; Drug Design; HEK293 Cells; Hep G2 Cells; Humans; Imidazoles; Male; Models, Molecular; Molecular Structure; Rats; Rats, Sprague-Dawley; Receptors, Serotonin; Scopolamine; Serotonin Antagonists; Structure-Activity Relationship

There is accumulating evidence indicating that long-term treatment with second-generation antipsychotics (SGAs) results in metabolic syndrome (MetS) and cognitive impairment. This evidence suggests an intrinsic link between antipsychotic-induced MetS and cognitive dysfunction in schizophrenia patients. Olanzapine is a commonly prescribed SGA with a significantly higher MetS risk than that of most antipsychotics. In this study, we hypothesized that olanzapine-induced MetS may exacerbate cognitive dysfunction in patients with schizophrenia.. A sample of 216 schizophrenia patients receiving long-term olanzapine monotherapy were divided into two groups, MetS and non-MetS, based on the diagnostic criteria of the National Cholesterol Education Program's Adult Treatment Panel III. We also recruited 72 healthy individuals for a control group. Cognitive function was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Plasma brain-derived neurotrophic factor (BDNF) and tumor necrosis factor-alpha (TNF-alpha) were measured by an enzyme-linked immunosorbent assay for 108 patients and 47 controls.. Among the 216 schizophrenia patients receiving olanzapine monotherapy, MetS was found in 95/216 (44%). Patients with MetS had more negative symptoms, higher total scores in PANSS (Ps<0.05) and lower immediate memory, attention, delayed memory and total scores in RBANS (Ps<0.01). Stepwise multivariate linear regression analysis revealed that increased glucose was the independent risk factor for cognitive dysfunction (t=-2.57, P=0.01). Patients with MetS had significantly lower BDNF (F=6.49, P=0.012) and higher TNF-alpha (F=5.08, P=0.026) levels than those without MetS. There was a negative correlation between the BDNF and TNF-alpha levels in the patients (r=-0.196, P=0.042).. Our findings provide evidence suggesting that the metabolic adverse effects of olanzapine may aggravate cognitive dysfunction in patients with schizophrenia through an interaction between BDNF and TNF-alpha.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Brain-Derived Neurotrophic Factor; Case-Control Studies; Cognitive Dysfunction; Cross-Sectional Studies; Female; Humans; Male; Metabolic Syndrome; Olanzapine; Schizophrenia; Treatment Outcome; Tumor Necrosis Factor-alpha; Young Adult

To assess the impact of reducing the dose of antipsychotics on cognition and dopaminergic D. Open-label prospective PET [. A tertiary care center outpatient setting.. Thirty-seven clinically stable participants with schizophrenia or schizoaffective disorder, aged 50 years or greater, and having been treated with olanzapine or risperidone monotherapy at the same dose for at least 6 months.. Gradual reduction in their olanzapine or risperidone daily dose of up to 40%.. Clinical and cognitive assessments, and [. Reducing the antipsychotic dose resulted in an increase in D. Our findings suggest that optimizing D

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Cognitive Dysfunction; Corpus Striatum; Female; Humans; Male; Middle Aged; Olanzapine; Positron-Emission Tomography; Psychotic Disorders; Raclopride; Receptors, Dopamine D2; Risperidone; Schizophrenia

Topics: Acute Disease; Adolescent; Adrenal Cortex Hormones; Adult; Anti-Anxiety Agents; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Antipsychotic Agents; Benzodiazepines; Cognitive Dysfunction; Diagnosis, Differential; Humans; Immunoglobulins; Lorazepam; Male; Mental Disorders; Olanzapine; Treatment Outcome; Young Adult