Elevated expression of integrin α_IIb β_IIIa in drug-naïve, first-episode schizophrenic patients

Abstract

Background

Patients with schizophrenia have an increased risk over the general public of developing cardiovascular illness. It is unknown if there are functional changes in platelet surface receptors in schizophrenia. We therefore analyzed the surface expression of glycoprotein (GP)Ib, the integrin receptor α_IIbβ_IIIa, CD62 (P-selectin), and CD63, and investigated platelet function in schizophrenic patients compared with healthy volunteers.

Methods

Nineteen drug-naive, first-episode patients with a DSM IV diagnosis of paranoid schizophrenia were compared with matched healthy controls. Flow cytometry was used to assess platelet surface expression levels of GPIb, α_IIbβ_IIIa, CD62, and CD63. Adenosine diphosphate-induced platelet aggregation was assayed.

Results

The schizophrenic patients had a significantly (p < .0001) increased number of 68145 ± 8260.1 α_IIbβ_IIIa receptors, platelet compared with 56235 ± 8079.4 receptors, platelet in healthy controls.

Conclusions

Patients with schizophrenia have increased platelet expression of α_IIbβ_IIIa, which may contribute to their increased risk of cardiovascular illness compared with the general population.

Introduction

Among psychiatric patients, there is an association between mental illness and poor physical health, and reports of sudden death are more common than in the general population Harris and Barraclough 1998, Philips 1934, Koran et al 1989, Makikyro et al 1998. In schizophrenia, while a major factor in premature sudden death is the high incidence of suicide Harris and Barraclough 1998, Ruschena et al 1998, Brown 1997, Black and Fisher 1992, Allebeck 1989, the majority of the excess mortality observed is attributable to the greater incidence of physical disorders Brown 1997, Allebeck 1989, Brown et al 2000, Goldman 1999, Mortensen and Juel 1993, Black 1998, Tsuang et al 1983, including an increased risk of development of cardiovascular disease compared with the general population Ruschena et al 1998, Allebeck 1989.

The biological basis of the link between schizophrenia and cardiovascular disease is unclear. Unhealthy lifestyle may have a major impact Brown et al 1999, Brown et al 2000, Phelan et al 2001; however, unrecognized underlying biological factors such as altered platelet function would also have an impact. Thrombosis in the coronary circulation results from a sudden aggregation of platelets Bhatt and Topol 2000, Andrews and Berndt 1998. This process is caused by a cascade of reactions, beginning with platelet adhesion via binding of the platelet surface glycoprotein complex GPIb-IX to von Willebrand factor (vWF), which binds to the subepithelium (Andrews and Berndt 1998). Adhesion triggers activation of the integrin α_IIbβ_IIIa, the most abundant integrin in platelets, which plays a crucial role in platelet spreading and aggregation and in normal hemostasis (Payastre et al 2000). Its activation results in platelet aggregation, activation Payastre et al 2000, Parise 1999, Litjens et al 2000, and secretion of granule glycoproteins including CD62 (P-selectin) and CD63, (lysosomal GP53) on the platelet surface. This process is normal in wound healing, but abnormal in pathologic conditions like myocardial infarction and stroke.

Recent studies demonstrating changes in platelet function associated with schizophrenia Modai et al 2000, Maguire et al 1997, Borcsiczky et al 1996, Jakovljevic et al 1997, Das and Khan 1998, Yao and van Kammen 1996, Tardito et al 2000, Ripova et al 1999, Ripova et al 1997, Berk et al 1999, Strunecka and Ripova 1999 have not addressed the expression of platelet adhesion, aggregation or activation proteins involved in thrombosis, such as GPIb, α_IIbβ_IIIa, CD62, and CD63. As there is increased incidence of and mortality from cardiovascular disease in schizophrenia Ruschena et al 1998, Allebeck 1989, we tested the hypothesis that such patients might have alterations in these proteins.