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

Abstract

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.

Autoantibody profiles associated with clinical features in psychotic disorders

“…Our trend finding of lower autoantibody counts in patients who were treated with clozapine is intriguing. Lower autoantibody counts in this patient group may reflect clozapine’s propensity to induce secondary antibody deficiency [ 27 ], but also raises the possibility that suppression of autoimmune processes could be a mechanism of action contributing clozapine’s superior clinical efficacy [ 28 ].…”