title: Psychiatric remission with warfarin: Should psychosis be addressed as plasminogen activator imbalance?
abstract: BACKGROUND
  Psychotic patients are at increased risk of thromboembolism that cannot be ascribed to physical restraint or medication. Patients with chronic schizophrenia or long-term depressive illness do not display ischemic brain injuries on magnetic resonance imaging, as expected in patients with thrombotic tendency, but atrophy of specific brain regions, which indicates abnormal neuronal plasticity.
  
  
  OBJECTIVE
  We postulate that a relationship between psychosis pathophysiology and thrombotic tendency may comprise proteins that participate not only in the anticoagulation-fibrinolysis mechanism, but also in neuronal plasticity.
  
  
  METHODS
  Five psychotic patients with thrombotic episodes on chronic warfarin therapy attained remission of psychotic symptoms and are free of psychotropic medication from 2 to 11years. All patients have at least one thrombophilia related to inhibition of plasminogen activators, including prothrombin G20.210A polymorphism, hyperhomocysteinemia, antiphospholipid antibody syndrome and protein C deficiency.
  
  
  CONCLUSIONS
  Plasminogen activators participate in blood clot dissolution and tissue repair, such as remodeling of hippocampus after stress, trauma, stroke or seizures. A significant prevalence of both thromboembolism and psychotic events can be seen in circumstances characterized by physiological or pathological inhibition of plasminogen activators, such as puerperium, confinement, polycystic ovary syndrome, antiphospholipid antibody syndrome and chronic inflammatory disorders.
  
  
  CONCLUSIONS
  Our findings suggest that normalization of plasminogen activator levels in the brain may induce long-term remission of psychotic symptoms. Randomized controlled studies may help clarify the role of anticoagulation in the treatment of psychosis.
authors.affiliation: Department of Hematology, Hospital Federal dos Servidores do Estado, Sacadura Cabral 178, Saúde, Rio de Janeiro, 20081-262, Brazil. sclapauch@ig.com.br
authors.forename: Silvia
authors.initials: S
authors.lastname: Hoirisch-Clapauch
authors.forename: Antonio E
authors.initials: AE
authors.lastname: Nardi
mesh_terms: D000293:Adolescent; D000328:Adult; D001938:Brazil; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009473:Neuronal Plasticity / Q000502:physiology*; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011618:Psychotic Disorders / Q000150:complications* / Q000188:drug therapy*; D012074:Remission Induction / Q000379:methods*; D013923:Thromboembolism / Q000150:complications*; D014859:Warfarin / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D014859:Warfarin; D010960:Plasminogen Activators