Abstract
Patients with psychosis, severe depression, or chronic stress are at increased risk
for thromboembolism. Evidence suggests that tissue plasminogen activator (tPA) and
plasminogen activator inhibitor-1 (PAI-1) imbalance may play an important role in
pathophysiology of mental and thromboembolic disorders. tPA facilitates clot dissolution
and participates in several brain functions, including response to stress, learning,
and memory. Depression is characterized by high PAI-1 levels, and conditions related
to a hypofibrinolytic status, such as polycystic ovary syndrome and metabolic syndrome,
are associated with an increased risk for both depression and cardiovascular events.
Depression/psychosis may occur when estrogen and progesterone levels decrease. Estrogen
inhibits synthesis of transforming growth factor-β (TGF-β), a protein increasing PAI-1
synthesis, whereas progesterone induces brain-derived neurotrophic factor release,
stimulating tPA expression in neurons. Synthetic progestogens (progestins) may cause
severe depression. Notably, progestin metabolites, which may prevent synthesis of
natural progesterone by feedback, do not cross the blood–brain barrier. Intense suprapubic
menstrual cramp, which may relate to difficulty to dissolve clots, correlates with
severe premenstrual tension. Exercise, which increases tPA synthesis, has antidepressive
and antithrombotic effects. We suggest that thromboembolism and some mental disorders
are mechanistically related: tPA–PAI-1 imbalance seems to be a common denominator.
Keywords
venous thromboembolism - depression - schizophrenia - psychosis - mental stress -
PAI-1 - plasminogen activator
