thromboplastin and Schizophrenia

Chlorpromazine (CPZ) is a widely used antipsychotic drug with antagonistic effect on dopamine receptors. Accumulating evidence has shown that CPZ plays a neuroprotective role in various models of toxicity and apoptosis. However, the underlying mechanism contributing to this protective effect remains unclear. Here, we evaluate the effect of CPZ on mitochondrial apoptotic pathway in the neuron system. Higher levels of B-cell lymphoma-2 (Bcl-2) and tissue factor (TF) but lower apoptotic rate were found in hippocampus of CPZ-treated schizophrenic patients compared with non-antipsychotic treated controls. Additionally, both short-term and long-term treatment of CPZ in rats could up-regulate the levels of Bcl-2 and TF with no cytotoxic effects. In the in vitro experiment, expression of Bcl-2 was up-regulated in the C6 glioma cells transfected with pEGFP-N1-TF recombinant plasmid. Furthermore, in another independent rat model of apoptosis, compared with the group administrated with alcohol only, the brains of the CPZ-pretreated rats showed lower expression of cleaved caspase-3, cytochrome c and Bax, but higher expression of Bcl-2 and TF. Our data demonstrate that CPZ exerts its neuronal protective effects through inhibiting the activation of mitochondrial apoptotic pathway by up-regulating TF expression, thus providing new insight into CPZ function and application.

Topics: Adult; Aged; Animals; Antipsychotic Agents; Apoptosis; Autopsy; bcl-2-Associated X Protein; Case-Control Studies; Caspase 3; Chlorpromazine; Cytochromes c; Gene Expression Regulation; Hippocampus; Humans; Male; Middle Aged; Mitochondria; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Schizophrenia; Thromboplastin

Patients with schizophrenia are at increased risk of venous thromboembolism. The mechanisms underlying this association are poorly understood.. We investigated whether there is a global hypercoagulable state in patients with schizophrenia utilising the overall haemostatic potential (OHP) assay which assesses overall coagulation potential (OCP), haemostatic potential (OHP) and fibrinolytic potential (OFP).. Citrated plasma was collected for OHP assays from patients with schizophrenia on long-term antipsychotic treatment and compared with healthy age- and sex-matched controls. Time courses of fibrin formation and degradation were measured by spectrophotometry (absorption of 405nm) after the addition of tissue factor and tissue plasminogen activator to plasma.. Ninety patients with schizophrenia (antipsychotic treatment-15.9±9.7years) and 30 controls were recruited. Patients with schizophrenia had higher rates of smoking and levels of inflammatory markers (high-sensitivity C-reactive protein and neutrophil-to-lymphocyte ratio) than controls. Whilst D-dimer, fibrinogen and platelet count did not differ between patients with schizophrenia and controls, the OCP (54.0±12.6 vs 45.9±9.1, p=0.002) and OHP (12.6±5.8 vs 7.2±3.7, p<0.001) were higher, and OFP was lower (76.6±9.8% vs 84.9±6.4%, p<0.001) in patients with schizophrenia, implying both a hypercoagulable and hypofibrinolytic state in these patients. Importantly, abnormalities in overall coagulation were independently predicted by levels of plasminogen-activator-inhibitor-1, fibrinogen, platelet count, inflammatory markers and plasma triglycerides, suggesting a multifactorial aetiology.. Patients with schizophrenia have evidence of a global hypercoagulable and hypofibrinolytic state which may contribute to their increased risk of venous thromboembolism.

Topics: Adult; Antipsychotic Agents; Blood Coagulation; Female; Fibrin; Humans; Male; Plasma; Schizophrenia; Spectrophotometry; Thrombophilia; Thromboplastin; Tissue Plasminogen Activator

Antipsychotic treatment has been repeatedly found to be associated with an increased risk for venous thromboembolism in schizophrenia. The extent to which the propensity for venous thromboembolism is linked to antipsychotic medication alone or psychosis itself is unclear. The objective of this study was to determine whether markers of thrombogenesis are increased in psychotic patients who have not yet been treated with antipsychotic medication.. We investigated the plasma levels of markers indicating activation of coagulation (D-dimers and Factor VIII) and platelets (soluble P-selectin, sP-selectin) in an antipsychotic-naive group of fourteen men and eleven women with acute psychosis (age 29.1 ± 8.3 years, body mass index 23.6 ± 4.7), and twenty-five healthy volunteers were matched for age, gender and body mass index.. D-dimers (median 0.38 versus 0.19 mg/l, mean 1.12 ± 2.38 versus 0.28 ± 0.3 mg/l; P = 0.003) and sP-selectin (median 204.1 versus 112.4 ng/ml, mean 209.9 ± 124 versus 124.1 ± 32; P = 0.0005) plasma levels were significantly increased in the group of patients with acute psychosis as compared with healthy volunteers. We found a trend (median 148% versus 110%, mean 160 ± 72.5 versus 123 ± 62.5; P = 0.062) of increased plasma levels of factor VIII in psychotic patients as compared with healthy volunteers.. The results suggest that at least a part of venous thromboembolic events in patients with acute psychosis may be induced by pathogenic mechanisms related to psychosis rather than by antipsychotic treatment. Finding an exact cause for venous thromboembolism in psychotic patients is necessary for its effective treatment and prevention.

Topics: Acute Disease; Adolescent; Adult; Antipsychotic Agents; Biomarkers; Case-Control Studies; Female; Fibrin Fibrinogen Degradation Products; Humans; Male; Middle Aged; P-Selectin; Psychotic Disorders; Schizophrenia; Thromboplastin; Venous Thromboembolism