title: Markers of low activity of tissue plasminogen activator/plasmin are prevalent in schizophrenia patients.
abstract: BACKGROUND
  Clot buster tissue plasminogen activator (tPA) and its end-product plasmin play a well-defined role in neurochemistry. They mediate a number of events that culminate in tolerance against excitotoxicity, hippocampal neurogenesis, synaptic remodeling, neuronal plasticity, cognitive and emotional processing. Abnormalities in these processes have been implicated in schizophrenia pathogenesis.
  
  
  METHODS
  Laboratory markers of low activity of tPA/plasmin were analyzed in 70 schizophrenia adults (DSM-IV), and 98 age-matched controls, consecutively selected at university hospitals.
  
  
  RESULTS
  All but two patients had positive markers (1-6, mean 2.1). Twenty-nine patients and 11 controls had hyperinsulinemia (44% vs. 11%) and 20 patients and 11 controls had hypertriglyceridemia (29% vs. 11%). Both insulin and triglycerides stimulate production of plasminogen activator inhibitor (PAI)-1, a major tPA inhibitor. Nineteen patients and six controls had hyperhomocysteinemia (27% vs. 6%), a condition that impairs tPA catalytic activity. Fifteen patients (22%) but no controls had free-protein S deficiency, a condition that reduces PAI-1 inhibition. Twenty-one patients (30%) but no controls had 1-3 antiphospholipid antibodies in medium or/high levels. Such antibodies are able to inhibit tPA/plasmin activity. Both PAI-1 polymorphism 4G/5G and heterozygous prothrombin G20210A were more prevalent in patients (60% vs. 48% and 2% vs. 1%, respectively), but difference lacked significance. PAI-1 polymorphism was synergistic with hyperinsulinemia. Protein C deficiency was not detected in patients or controls.
  
  
  CONCLUSIONS
  We have found a high prevalence of markers of low tPA/plasmin activity in a sample of schizophrenia patients. Our findings should be validated in large studies, preferably in medication-naïve patients.
authors.affiliation: Department of Hematology, Hospital Federal dos Servidores do Estado, Ministry of Health, Rio de Janeiro, Brazil. Electronic address: sclapauch@ig.com.br.
authors.forename: Silvia
authors.initials: S
authors.lastname: Hoirisch-Clapauch
authors.affiliation: Institute of Psychiatry, Federal University of Rio de Janeiro, National Institute for Translational Medicine, INCT-TM, CNPq, Brazil.
authors.forename: Antonio E
authors.initials: AE
authors.lastname: Nardi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D005260:Female; D005341:Fibrinolysin / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012559:Schizophrenia / Q000097:blood* / Q000235:genetics; D010959:Tissue Plasminogen Activator / Q000097:blood* / Q000235:genetics; D055815:Young Adult
chemical_list: D015415:Biomarkers; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin
keywords: Antiphospholipid antibodies; Pathophysiology; Plasminogen activator; Plasminogen activator inhibitor-1; Protein S deficiency; Schizophrenia