Markers of low activity of tissue plasminogen activator/plasmin are prevalent in schizophrenia patients

作者：Hoirisch Clapauch Silvia^*; Nardi Antonio E

来源：Schizophrenia Research, 2014, 159(1): 118-123.

DOI：10.1016/j.schres.2014.08.011

• Antiphospholipid antibodies
• Pathophysiology
• Plasminogen activator
• Plasminogen activator inhibitor-1
• Protein S deficiency
• Schizophrenia

Introduction: 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.
Conclusion: 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-naive patients.

• 出版日期2014-10