Primary antiphospholipid syndrome and severe mental illness: preliminary results of a long-term case-control study

Lupus anticoagulant, multiple or high-titer antiphospholipid antibodies identify patients at high risk of thrombosis and obstetric complications. We aimed to determine whether this antibody profile also increases the risk of severe mental illness (SMI). This study included 34 adults with primary antiphospholipid syndrome (APS), regularly screened for mental disorders for at least 5 years. Data from 19 APS+SMI patients without cerebral ischemia were compared with those of 15 APS controls never diagnosed with SMI . Of the 12 APS+SMI who experienced psychosis, four were treatment-resistant. Four patients experienced severe unipolar depression, two of them were treatment-resistant. Fourteen were highly impulsive, ten of them also had psychosis or severe unipolar depression. Sixteen APS+SMI individuals and nine controls had lupus anticoagulant (RR: 1.4; 95% CI: 0.8-2.2). Thirteen APS+SMI and none of the controls had multiple antibodies (RR: 21; 95% CI: 1.3-336). Ten APS+SMI and one control had either a strong lupus anticoagulant, i.e. dRVVT ≥ 2 or anticardiolipin/anti-β2-glycoprotein I antibody titers ≥ 80 GPL/MPL, range 80–314 GPL/MPL (RR: 7; 95% CI: 1.1-54). The APS+SMI group had more venous or arterial thrombosis per subject than the control group (1.5 vs 0.8). The frequency of obstetric complications was similar in both groups. Our preliminary results suggest that patients with multiple or high-titer antiphospholipid antibodies are at high risk of psychosis, severe depression, and/or high impulsivity. Future studies are needed to establish the role of antibody-reduction protocols in SMI associated with antiphospholipid antibodies, especially in patients resistant to standard treatment. • Severe mental illness are associated with atrophy of brain areas. • The fibrinolytic system is involved in adult neurogenesis and synaptic plasticity. • Antiphospholipid antibodies (APLA) are potent fibrinolysis inhibitors. • Multiple or high-titer APLA increase the risk of thrombosis and pregnancy complications. • In our study, these antibody profiles increased the risk of severe mental illness.