Prevalence of Clinical and Laboratory Markers of Hypofibrinolysis in Psychotic Patients
Condition: Insulin Resistance; Thrombophilia; Psychosis
MeSH terms: Thrombophilia; Insulin Resistance
Study type: Observational

Summary: 
      At the Thrombophilia Clinic of the Hospital Federal dos Servidores do Estado do Rio de
      Janeiro there is a high prevalence of acute psychotic episodes, which allows the
      investigators to raise the suspicion that the thrombotic tendency or hypofibrinolysis play a
      role in the onset of the disease. It is striking that most of these patients, after some time
      on anticoagulants, no longer need to take psychiatric medication.
    

Detailed description: 
      If the thrombotic tendency plays a significant role in the etiology of psychosis, one would
      expect to find ischemic brain injuries in neuroimaging studies, but it does not happen.
      Therefore, if there is a correlation between thrombotic tendency-hypofibrinolysis and
      psychosis it is likely to occur at the biochemical level, such as in neuronal transmission.

      The investigators hypothesis is that mechanisms that inhibit tissue plasminogen activator
      (t-PA) and therefore promote hypofibrinolysis, are directly or indirectly involved in the
      genesis of psychosis, because t-PA participates in neuronal plasticity and low t-PA levels
      are related to dementia.

      Hypofibrinolysis due to t-PA inhibition can be seen in:

        -  Insulin resistance, when the pancreas must produce large amounts of insulin and
           proinsulin by feedback. If pancreatic reserve is inadequate, the result is diabetes
           mellitus. If the response is adequate, proinsulin stimulates the production of PAI-1
           (plasminogen activator inhibitor 1. PAI-1 inhibits the formation of plasmin, whose
           function is to dissolve fibrin which makes up the clot. Obesity, certain infections and
           inflammations potentiate insulin resistance.

        -  Antiphospholipid antibody syndrome.

        -  PAI-1 4G/5G or 4G/4G polymorphism.

      Some hypofibrinolysis indicators are:

        -  severe dysmenorrhea, because strong uterine contractions are necessary to expel
           undissolved clots.

        -  PCOS because plasmin is required to activate some metalloproteinases involved in ovary
           remodelling.

        -  early pregnancy losses, as some metalloproteinases involved in placental angiogenesis
           are activated by plasmin,

        -  preeclampsia and eclampsia, as metalloproteinases that dissolve elastic fibers of the
           placental vessels, to create a low flow resistance, are activated by plasmin. Vascular
           endothelial growth factor (VEGF), a protein that restricts glomerular porosity, is also
           activated by plasmin,

        -  sudden death and heart attack before age 50 in first degree relatives.

      On physical exam, acanthosis, high body mass index, and in women, hirsutism and acne are
      indirect indicators of insulin resistance. Livedo suggest antiphospholipid antibody syndrome.

      This study intents to investigate the prevalence of hypofibrinolysis markers, such as PAI-1
      4G/5G and 4G/4G, protein S deficiency, antiphospholipid antibodies and prothrombin G20210A,
      in psychotic patients.
    

Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Psychotic patients treated at IPUB-UFRJ, comprising patients with schizophrenia,
        schizoaffective disorders, bipolar disorders (mania or depressive episodes, provided that
        the patient has shown an acute psychotic episode in the last two years.

        Age-matched control group
      
Keywords: Thrombophilia tests; Hypofibrinolysis; Fibrinolysis