Apoptosis and schizophrenia:: A pilot study based on dermal fibroblast cell lines

Introduction: The aim of this study was to investigate whether there is an increased susceptibility to apoptosis in cultured fibroblasts from patients with schizophrenia. Method: Dermal fibroblasts were collected and cultured from three groups: patients with schizophrenia, patients with non-schizophrenic psychosis, and healthy comparison subjects. Susceptibility to apoptosis was measured at the level of degradation product (proportion of cells in the sub-GO cell cycle fraction in which apoptotic bodies accumulate), pro-apoptotic effector (activated caspase-3), and molecular regulators (P53, Bax and Bcl-2). Cell lines were studied under both basal culture and cycloheximide (an apoptotic inducer) exposure conditions. Results: Consistent with increased susceptibility to apoptosis, the proportion of sub-GO cells under basal conditions was significantly larger in the schizophrenia group, compared to the non-schizophrenic psychosis group. However when apoptosis was stimulated with cycloheximide, the schizophrenia group showed an attenuated caspase-3 response. The pattern of correlations between regulators, caspase-3 and the proportion of sub-GO cells was different in the schizophrenia group, consistent with group-specific apoptotic pathway dysregulation. Conclusion: The study demonstrated anomalous apoptotic mechanisms in schizophrenia, which appear not to affect nonschizophrenia psychosis patients. The detection of these anomalies in fibroblasts suggests that altered apoptosis may be observable in all somatic cell types in schizophrenia. (c) 2006 Elsevier B.V All rights reserved.