Role of tissue plasminogen activator and plasminogen activator inhibitor as potential biomarkers in psychosis.

The identification of biological markers for psychosis has an impact on its diagnosis, prognosis, and likelihood of treatment response. Tissue plasminogen activator (tPA) is involved in important functions such as synaptic plasticity, long-term potentiation and neurogenesis. Plasminogen activator inhibitor (PAI-1) is the most important inhibitor of tPA. Preliminary studies have shown that schizophrenia patients have lower tPA and higher PAI-1 levels than the general population. The association of tPA and PAI-1 abnormalities with psychotic spectrum disorders, however, remains elusive. Our primary objective was to assess the plasma levels of tPA and PAI-1 in patients experiencing acute psychotic episodes as compared to those in healthy controls. In this prospective case-control study, we collected peripheral blood samples from psychiatric inpatients and healthy age, gender and race-matched subjects and determined plasma levels of tPA and PAI-1 by enzyme-linked immune-absorbent assays. Plasma levels of PAI-1 in patients with schizoaffective disorder were significantly lower as compared to those in control subjects (P = 0.03). tPA was lower in cases as compared to controls although it did not reach statistical significance. Asian patients and controls had lower PAI-1 levels. Further, Asian patients with schizoaffective disorder had significantly lower PAI-1 level compared to Asian patients with schizophrenia. Our results indicate that patients with schizoaffective disorder have lower PAI-1 levels than those with schizophrenia, affective psychosis, and healthy controls. Further studies are warranted to explore the potential of PAI-1 as a biomarker for diagnosing schizoaffective disorder.