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

BACKGROUND: Previous studies have demonstrated significantly higher blood titers of platelet-associated autoantibodies (PAA) in adult schizophrenia patients compared to normal healthy subjects. In addition, young adult schizophrenia patients at their early stages of the disorder displayed higher PAA titers than older patients with longer duration of the disorder. AIM: To assess longitudinally the blood titers of PAA in inpatients with childhood-onset schizophrenia at admission, after short- and long-term follow-up, and the correlation of these titers with the response to clozapine and other antipsychotic treatments. METHODS: Thirty children, age range of 6-12 (mean ± SD: 9.6 ± 1.5 years), with DSM-IV TR schizophrenia in active psychotic state were assessed 3 times: at baseline, after short-term (8-17 weeks; n = 26) and after long-term follow-up (33-170 weeks; n = 19). The blood titers of PAA were analyzed using ELISA and expressed by a linear optical density (OD) scale. A test recording >1.4 OD units was predefined as the positive cutoff value. RESULTS: On long-term follow-up, 9 out of the 17 children who were PAA-positive at baseline became PAA-negative: 7 already after 2 months of clozapine treatment and 2 following 3 years of risperidone treatment. Eight children remained PAA-positive during the entire study period. There was no significant correlation between the clinical improvement (as assessed by change in the Positive and Negative Syndrome Scale score) and the alteration in PAA levels (n = 19, r = -0.4, p = 0.088). CONCLUSIONS: High rates of positive PAA in COS patients may indicate an active autoimmune process in early-onset schizophrenia. It is concluded that PAA may serve as a biomarker for the diagnosis of COS, but does not predict the response to treatment. A transition to a PAA-negative status does not indicate an improvement in psychosis. © 2015 S. Karger AG, Basel.

High circulatory titer of platelet-associated autoantibodies in childhood onset schizophrenia and its diagnostic implications.

BACKGROUND: It has been suggested that the etiology of schizophrenia, in a distinct group of patients, originates from an autoimmune reaction against platelets. Previous studies have demonstrated significantly higher blood titers of platelet-associated autoantibodies (PAA) in adult schizophrenia patients as compared to normal healthy subjects. In addition, young adult schizophrenia patients at their early stages of the disorder displayed higher PAA titers than older patients with longer duration of the disorder. AIM: To assess the blood titers of PAA in children with schizophrenia as compared to matched control subjects without psychotic disorders, as a possible diagnostic parameter. METHODS: Twenty-nine children with DSM-IV schizophrenia in the active psychotic state, with an age range of 6-12 years (mean ± SD: 9.6 ± 1.5 years), with average Positive and Negative Syndrome Scale scores of 108 ± 19.2, were assessed. The control group consisted of 25 children with DSM-IV conduct disorder in a similar age range of 5-12 years (mean ± SD: 9.5 ± 1.6 years). The blood titers of PAA were evaluated 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 1.4 OD units was predefined as positive. RESULTS: The titers of PAA of children with schizophrenia (1.9 ± 0.5 OD units, range: 0.7-2.44 units) were significantly (p < 0.00001) higher than those of the control group (1.0 ± 0.4 OD units, range: 0.45-2.28 units). In 83% of the children with schizophrenia (24 out of the 29 patients) a positive test, i.e. OD >1.4, was detected. In contrast, in the control group, only 12% (3 of the 25 subjects) displayed a positive test, p < 0.00001. CONCLUSIONS: High titers of PAA in children with schizophrenia as compared with nonpsychotic controls may indicate an active autoimmune process in the early onset of schizophrenia. The PAA level may therefore provide a supportive diagnostic biomarker for childhood schizophrenia.

Blind verification of elevated platelet autoantibodies in serum of schizophrenic patients--part II: adult subjects.

BACKGROUND: In our preceding study, we assayed in a blind fashion the blood sera of young normal subjects and schizophrenic patients for levels of platelet autoantibodies (PAA). The recorded PAA titers of the schizophrenic patients were significantly higher than those of the normal subjects. This observation has lent support to this test being used as an objective evaluation of schizophrenia in young subjects in the future. In addition, this finding strongly suggested that the etiology of a distinct group of sufferers of this disorder could have originated from an autoimmune reaction against platelets which can, under certain conditions, cross-react with brain tissue. AIMS: In the present study, PAA titers in the sera of adult schizophrenic patients and matched normal subjects were determined analogously to the preceding study. The effect of hospitalization and drug treatments on the apparent blood test scoring in adult subjects could thus be evaluated. METHODS: A total of 46 schizophrenia patients (30 men and 16 women) aged 19-45 years (mean +/- SD: 31.7 +/- 8.0 years) with a minimum score of 60 on the Positive and Negative Symptom Scale and 43 healthy control subjects (22 men and 21 women) aged 21-44 years (mean +/- SD: 31.9 +/- 6.9 years) participated in the study. The blood titers of PAA were evaluated in a single-blind fashion using an optimized ELISA test scored by optical density (OD) units. A positive test was defined as a value above 1.3 OD units. RESULTS: The titers of PAA in the group of schizophrenic patients (1.1 +/- 0.55 OD units, range: 0.360-2.285 OD units) were significantly higher in comparison to those of the healthy control subjects (0.81 +/- 0.37 OD units, range: 0.360-1.704 OD units; p = 0.004, two-tailed unpaired t-test). Significantly more schizophrenic patients showed a positive test (15 patients out of 46) than the control subjects (5 out of 43). However, significantly higher OD values of 1.55 +/- 0.5 were recorded in the group of patients with less than 3 years of registered disease (n = 16, age 19-30 years), while in the group with 4-20 years of hospitalization (n = 30, age 24-45 years) the recorded OD values (0.85 +/- 0.4 OD units) were practically indistinguishable from those of the control group. CONCLUSIONS: In the adult schizophrenic patients, the PAA blood test remains valid for patients who were hospitalized for less than 3 years. Drug treatment, length of disease and age can be assumed to reduce the PAA level considerably.

Blind verification of elevated platelet autoantibodies in serum of schizophrenic patients--part I: young subjects.

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.