quetiapine-fumarate and Cognitive-Dysfunction

Relapse is distressingly common after the first episode of psychosis, yet it is poorly understood and difficult to predict. Investigating changes in cognitive function preceding relapse may provide new insights into the underlying mechanism of relapse in psychosis. We hypothesized that relapse in fully remitted first-episode psychosis patients was preceded by working memory deterioration.. Visual memory and verbal working memory were monitored prospectively in a 1-year randomized controlled trial of remitted first-episode psychosis patients assigned to medication continuation (quetiapine 400 mg/day) or discontinuation (placebo). Relapse (recurrence of positive symptoms of psychosis), visual (Visual Patterns Test) and verbal (Letter-Number span test) working memory and stressful life events were assessed monthly.. Remitted first-episode patients (n = 102) participated in the study. Relapsers (n = 53) and non-relapsers (n = 49) had similar baseline demographic and clinical profiles. Logistic regression analyses indicated relapse was associated with visual working memory deterioration 2 months before relapse [odds ratio (OR) 3.07, 95% confidence interval (CI) 1.19-7.92, P = 0.02], more stressful life events 1 month before relapse (OR 2.11, 95% CI 1.20-3.72, P = 0.01) and medication discontinuation (OR 5.52, 95% CI 2.08-14.62, P = 0.001).. Visual working memory deterioration beginning 2 months before relapse in remitted first-episode psychosis patients (not baseline predictor) may reflect early brain dysfunction that heralds a psychotic relapse. The deterioration was found to be unrelated to a worsening of psychotic symptoms preceding relapse. Testable predictors offer insight into the brain processes underlying relapse in psychosis.

Topics: Adult; Antipsychotic Agents; Cognitive Dysfunction; Disease Progression; Double-Blind Method; Female; Humans; Male; Memory, Short-Term; Prognosis; Psychotic Disorders; Quetiapine Fumarate; Recurrence; Remission Induction; Stress, Psychological; Time Factors; Young Adult

Low-dose lithium (LD-Li) has been shown to rescue cognitive impairment in mouse models of short-term mild cognitive impairment, dementia, and schizophrenia. However, few studies have characterized the effects of LD-Li, alone or in conjunction with anti-psychotics, in the mouse model of MK801-induced long term cognitive impairment.. Compared to the QTP-mt group, the LD-Li + QTP group showed greatly improved cognitive performance on all measures between experimental days 29 and 85. QTP-mt improved behavioral measures compared to untreated controls, but the effects persisted only from day 29 to day 43. These data suggest that LD-Li + QTP is superior to QTP-mt for improving long-term cognitive impairments in the MK801 mouse model.. There is no medical consensus regarding lithium use in patients with schizophrenia.. More pre-clinical and clinical studies are needed to further investigate effective treatment strategies for patients with long-term cognitive impairments, such as chronic schizophrenia.

Topics: Animals; Cognition; Cognitive Dysfunction; Disease Models, Animal; Dizocilpine Maleate; Humans; Lithium; Mice; Pilot Projects; Quetiapine Fumarate; Task Performance and Analysis

Chemotherapy is considered a major choice in cancer treatment. Unfortunately, several cognitive deficiencies and psychiatric complications have been reported in patients with cancer during treatment and for the rest of their lives. Doxorubicin (DOX) plays an important role in chemotherapy regimens but affects both the central and peripheral nervous systems. Antipsychotic drugs alleviate the behavioral symptoms of aging-related dementia, and the atypical class, quetiapine (QUET), has been shown to have beneficial effects on various cognitive impairments. The present investigation aimed to determine the possible mechanism underlying the effect of thirty-day administrations of QUET (10 or 20 mg/kg, p.o.) on DOX-induced cognitive deficits (DICDs). DICDs were achieved through four doses of DOX (2 mg/kg, i.p.) at an interval of seven days during drug treatment. Elevated plus maze (EPM), novel object recognition (NOR), and Y-maze tasks were performed to confirm the DICDs and find the impact of QUET on them. The ELISA tests were executed with oxidative [malondialdehyde (MDA), catalase, and reduced glutathione (GSH)], inflammatory [cyclooxygenase-2 (COX-2), nuclear factor kappa B (NF-κB), and tumor necrosis factor-alpha (TNF-α)], and apoptosis [B-cell lymphoma 2 (Bcl2), Bcl2 associated X protein (Bax), and Caspase-3] markers were assessed in the brain homogenate to explore the related mechanisms. DICD lengthened the transfer latency time in EPM, shortened the exploration time of the novel object, reduced the discrimination ability of the objects in NOR, and lowered the number of arm entries and time spent in the novel arm. QUET alleviated DICD-related symptoms. In addition, QUET reduced neuronal oxidative stress by reducing MDA and elevating GSH levels in the rat brain. Moreover, it reduced neuronal inflammation by controlling the levels of COX-2, NF-κB, and TNF-α. By improving the Bcl-2 level and reducing both Bax and Caspase-3 levels, it protected against neuronal apoptosis. Collectively, our results supported that QUET may protect against DICD, which could be explained by the inhibition of neuronal inflammation and the attenuation of cellular apoptosis protecting against oxidative stress.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Caspase 3; Cognition; Cognitive Dysfunction; Cyclooxygenase 2; Doxorubicin; Inflammation; Neuroinflammatory Diseases; NF-kappa B; Oxidative Stress; Quetiapine Fumarate; Rats; Tumor Necrosis Factor-alpha

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

The cognitive impairment associated with schizophrenia is highly prevalent and affects the overall functioning of subjects. The stimulation of the serotonin 1A receptor is a primary characteristic of some atypical antipsychotic drugs. We measured the levels of cognitive impairment using the Morris water maze test and protein kinase A activity in hippocampal neurons on presynaptic and postsynaptic serotonin 1A receptors to investigate the effect of dizocilpine-induced cognitive impairment associated with atypical antipsychotic drugs in rats treated by quetiapine alone or combined with WAY100635/tandospirone. The results of the Morris water maze test presented evidence that quetiapine alone alleviated the cognitive impairment associated with atypical antipsychotic drugs induced by dizocilpine. However, quetiapine plus WAY100635 induced no improvement of cognitive impairment associated with atypical antipsychotic drugs. The results of protein kinase A assay suggested that neither quetiapine alone nor in combination with tandospirone, but not quetiapine plus WAY100635, raised protein kinase A activity in hippocampus neurons. The present study demonstrated the key role of presynaptic serotonin 1A receptors on the therapeutic effect of quetiapine on cognitive impairment associated with atypical antipsychotic drugs. Moreover, that protein kinase A activity in hippocampal cells is involved in the mechanism of quetiapine's effect on cognitive impairment associated with atypical antipsychotic drugs.

Topics: Animals; Antipsychotic Agents; Cognitive Dysfunction; Cyclic AMP-Dependent Protein Kinases; Hippocampus; Male; Neurons; Quetiapine Fumarate; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT1A; Receptors, Presynaptic; Schizophrenia

Diabetic patients are at increased risk for developing memory and cognitive deficit. Prior studies indicate that neuroinflammation might be one important underlying mechanism responsible for this deficit. Quetiapine (QTP) reportedly exerts a significant neuroprotective effect in animal and human studies. Here, we investigated whether QTP could prevent memory deterioration and cognitive impairment in a streptozotocin- (STZ-) induced diabetic mouse model. In this study, we found that STZ significantly compromised the behavioral performance of mice in a puzzle box test, but administering QTP effectively attenuated this behavioral deficit. Moreover, our results showed that QTP could significantly inhibit the activation of astrocytes and microglia in these diabetic mice and reduce the generation and release of two cytokines, tumor necrosis factor-

Topics: Animals; Astrocytes; Chemokine CCL2; Cognition Disorders; Cognitive Dysfunction; Diabetes Mellitus, Experimental; Disease Models, Animal; Executive Function; Male; Memory; Mice; Mice, Inbred C57BL; Microglia; Neuroprotective Agents; Quetiapine Fumarate; Streptozocin; Tumor Necrosis Factor-alpha

Capgras delusion is a delusional misidentification syndrome, in which the patient is convinced that someone that is well known to them, usually a close relative, has been replaced by an impostor or double. Although it has been frequently described in psychotic syndromes, including paranoid schizophrenia, over a third of the documented cases of Capgras delusion are observed in patients with organic brain lesions or neurodegenerative disease, including Parkinson's Disease. Variants of Capgras involving animals or inanimate objects have also been described. The etiology of Capgras in Parkinson's remains unclear, but may arise from a combination of factors, such as frontal lobe dysfunction and dopaminergic medication.. We present the case of a 53-year old right-handed female with Parkinson's disease who developed Capgras delusion during treatment with dopamine agonists and Levodopa/Carbidopa. She became convinced that her pet dogs and the plants in her garden had been substituted by identically looking ones. Our patient was initially treated with Quetiapine, with no improvement, and subsequently treated with Clozapine, which lead to partial regression of her symptoms. Neuropsychological Evaluation showed Mild Cognitive Impairment in Executive Functions.. Given the clinical history, onset and evolution of symptoms we believe our patient's delusion resulted from the overlap of dopaminergic medication and Mild Cognitive Impairment in executive functions. Zoocentric Capgras, the variant we describe, has been rarely described in scientific literature, and we believe it is of interest due to its unusual characteristics.

Topics: Animals; Antiparkinson Agents; Antipsychotic Agents; Capgras Syndrome; Carbidopa; Clozapine; Cognitive Dysfunction; Delusions; Dibenzothiazepines; Dogs; Dopamine Agonists; Drug Therapy, Combination; Female; Humans; Levodopa; Parkinson Disease; Pets; Plants; Quetiapine Fumarate

Topics: Aged, 80 and over; Antipsychotic Agents; Cognitive Dysfunction; Delusional Parasitosis; Dementia, Vascular; Female; Humans; Hyperglycemia; Leukoaraiosis; Quetiapine Fumarate