Title:Low Activity of Plasminogen Activator: A Common Feature of Non- Iatrogenic Comorbidities of Schizophrenia
Volume: 14
Issue: 3
Author(s): Silvia Hoirisch-Clapauch and Antonio E. Nardi
Affiliation:
Keywords:
Comorbidity, drug naïve, medication naïve, metabolism, plasminogen activator, schizophrenia.
Abstract: Understanding the pathogenesis of non-iatrogenic comorbidities of schizophrenia may
provide insights into the pathogenesis of schizophrenia itself. First-episode, drug-naïve schizophrenia
patients are at high risk of thromboembolic events, diseases related to substance abuse, sexual
dysfunction, reproductive disorders, inflammatory and autoimmune diseases, as well as complications
of hyperinsulinemia or hyperhomocysteinemia. This review focuses on the role of reduced plasminogen activator activity
in non-iatrogenic comorbidity of schizophrenia. By preventing thrombus dissolution, low tissue plasminogen activator
activity increases the risk of thrombotic events. Components of the plasminogen activator system also play a key role in
reproduction. Both illicit drugs and tobacco increase plasminogen activator levels in the central nervous system, which
seems to relieve symptoms of the mental disorder. Chronic alcoholism, sexual dysfunction, inflammatory and
autoimmune disorders, and complications of hyperinsulinemia or hyperhomocysteinemia are somehow related to low
plasminogen activator activity. Plasminogen activator mediates several neurochemical processes that seem to prevent or
reverse gray-matter atrophy seen in first-episode schizophrenia patients. Such processes include cleavage of brain-derived
neurotrophic factor precursor to an anti-apoptotic neurotrophin and activation of N-methyl-D-aspartate receptor.
Controlled, randomized studies are needed to determine if measures aimed at correcting plasminogen activator activity
can improve the quality of life, reduce morbidity and mortality rates, and particularly improve the course of
schizophrenia.
