Blind Verification of Elevated Platelet Autoantibodies in Serum of Schizophrenic Patients – Part I: Young Subjects

Abstract

Background: It has been hypothesized that the etiology of schizophrenia, in a distinct group of patients, originates from an autoimmune reaction against platelets. Previous open screenings have recorded significantly higher blood titers of platelet-associated autoantibodies (PAA) in schizophrenic patients as compared to normal healthy subjects. In addition, young schizophrenic patients at the early stages of their disorder displayed higher PAA titers than older patients with a longer duration of the disorder. A blood test based on these observations was proposed. Aim: To verify by a blind test a significant difference in PAA between young schizophrenic patients and matched healthy control subjects, for the validation of a blood test for schizophrenia. Methods: A total of 36 young schizophrenic patients in an active psychotic state, aged 13–20 years (mean ± SD: 16.2 ± 2.1 years) with an average PANSS score of 115.6 ± 14.5 and illness duration of 9.5 ± 9.4 months, were examined. The control group consisted of 49 healthy young subjects between the ages of 13 and 21 years (16.2 ± 2.2 years). The blood titers of PAA were evaluated blindly using an optimized ELISA test, expressed by a linear optical density (OD) scale. The blood samples of all participants were tested anonymously, and were scored under a code number. A test recording above 1.3 OD units was defined as positive. Results: The PAA titers of schizophrenia patients (1.6 ± 0.4 OD units, range: 0.7–2.3 OD units) were significantly higher than those of the control group (1.0 ± 0.4 OD units, range: 0.4–1.8 OD units; p < 0.0001). In 61% of the young schizophrenic patients (22 out of the 36 patients), a positive result (OD >1.3 units) was recorded. In the control group, only 12.2% (6 of the 49 subjects) displayed a positive result (p < 0.0001). Conclusions: These findings support further assessment of PAA titers as a potential biomarker for patients with clinical signs and symptoms of schizophrenia.

Effect of Clozapine and Other Antipsychotics on the Level of Platelet-Associated Autoantibodies in Children with Schizophrenia: A Longitudinal Follow-Up Study

“…It has been previously reported that the serum of schizophrenia patients is enriched with PAA [4,6,10,11] and an inverse correlation has been detected between the duration of disease and the level of PAA titers [10,11,16]. The main objective of the present study was to assess the impact of clozapine and nonclozapine antipsychotics on PAA levels in COS patients and to evaluate a possible relationship between clinical improvement and alterations in PAA levels.…”

“…The presence of high PAA titers may have indicated an active autoimmune process associated with the pathophysiology of COS, and it was suggested that a PAA-positive status may serve as an immune biomarker of COS [16]. We have previously observed [5,8,10] that the PAA levels in adolescent and adult schizophrenia patients were not influenced by treatment with any of the antipsychotic medications, except clozapine. Similarly, in the present study it was clearly demonstrated that there was no correlation between changes in PAA status and the clinical improvement following antipsychotic treatment.…”

“…A procedure outlined in our previous publications [9,10,11] was used. Ten milliliters of venous blood was collected from each of the participants.…”

“…Previous studies have demonstrated significantly higher blood titers of PAA in adult schizophrenia patients compared to normal healthy subjects [4,5,6]. In addition, young schizophrenia patients at their early stages of the disorder displayed higher PAA titers than older patients with long duration of the disorder [9,10,11]. …”

High Circulatory Titer of Platelet-Associated Autoantibodies in Childhood Onset Schizophrenia and Its Diagnostic Implications

“…Previous studies have demonstrated significantly higher blood titers of PAA in adult schizophrenia patients as compared to normal healthy subjects [4,5,6]. In addition, young schizophrenia patients at their early stages of the disorder displayed higher PAA titers than older patients with longer duration of the disorder [9,10,11]. …”