LAUSR

Protein S, a natural anticoagulant with profibrinolytic properties, plays an important role in the central nervous system. Studies with cortical neurons showed that protein S binding to TAM(Tyro3, Axl, andMer) receptors enhances proliferation and differentiation of adult neural stem cells. The mechanism involves increased expression of anti-apoptotic protein Bcl-2, reduced expression of pro-apoptotic protein p53, microglial inhibition and synaptic pruning [1,2]. Protein S also seems to protect ischemic mouse neurons from hypoxia/reoxygenation-induced apoptosis, in doses that do not significantly improve post-ischemic flow [3]. While inherited protein S deficiency is a rare autosomal dominant disorder, acquired deficiency is not uncommon andmay result from reduced synthesis (e.g. estrogen use, pregnancy, the puerperium, hepatic insufficiency), increased excretion (e.g. nephrotic syndrome), consumption (e.g. disseminated intravascular coagulation) or autoantibodies (e.g. autoimmune disease and HIV infection). Since protein S bound toC4b-bindingprotein is inactive, conditions accompanied by increased levels of this complement system protein, such as systemic inflammation, are characterized by low protein S activity. Knowing that the puerperium, systemic lupus erythematosus, inflammatory bowel disease, HIV infection and other conditions characterized by low protein S activity are associated with an increased risk of psychosis,we decided to study the prevalence of psychotic symptoms and psychotic disorders in individuals with inherited protein S deficiency. From July to November 2016, adults with a thrombotic event or adverse pregnancy outcome related to protein S deficiency attending a tertiary care hospital in Rio de Janeiro, Brazil were selected. All were classified as type 1 deficiency (reduction in total and free protein S levels). Their first-degree adult relatives were screened for protein S deficiency. Index cases and their relatives with low protein S levels were invited to participate in this study. Those who accepted underwent clinical evaluation and a semistructured psychiatric interview. Since antiphospholipid antibodies may interfere with the measurement of protein S functional levels, all participants were screened for anticardiolipin antibodies and for lupus anticoagulant, but not for antiβ2 glycoprotein 1 antibodies. Mental disorders were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, DSM-5 [4]. Participants were