title: Increased susceptibility to apoptosis in cultured fibroblasts from antipsychotic-naïve first-episode schizophrenia patients.
abstract: Altered apoptosis has been proposed as a potential mechanism involved in the abnormal neurodevelopment and neurodegenerative processes associated with schizophrenia. The aim of this study was to investigate in primary fibroblast cultures whether antipsychotic-naïve patients with first-episode schizophrenia have greater apoptotic susceptibility than healthy controls. Cell growth, cell viability and various apoptotic hallmarks (caspase-3 activity, translocation of phosphatidylserine, chromatin condensation and gene expression of AKT1, BAX, BCL2, CASP3, GSK3B and P53) were measured in fibroblast cultures obtained from skin biopsies of patients (n = 11) and healthy controls (n = 8), both in basal conditions and after inducing apoptosis with staurosporine. Compared to controls, cultured fibroblasts from patients showed higher caspase-3 activity and lower BCL2 expression. When exposed to staurosporine, fibroblasts from patients also showed higher caspase-3 activity; a higher percentage of cells with translocated phosphatidylserine and condensed chromatin; and higher p53 expression compared to fibroblasts from controls. No differences in cell viability or cell growth were detected. These results strongly support the hypothesis that first-episode schizophrenia patients may have increased susceptibility to apoptosis, which may be involved in the onset and progression of the disease.
authors.affiliation: Dept. Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. Electronic address: pgasso@ub.edu.
authors.forename: Patricia
authors.initials: P
authors.lastname: Gassó
authors.forename: Sergi
authors.initials: S
authors.lastname: Mas
authors.forename: Oriol
authors.initials: O
authors.lastname: Molina
authors.forename: Amalia
authors.initials: A
authors.lastname: Lafuente
authors.forename: Miquel
authors.initials: M
authors.lastname: Bernardo
authors.forename: Eduard
authors.initials: E
authors.lastname: Parellada
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D002843:Chromatin / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D008297:Male; D010718:Phosphatidylserines / Q000378:metabolism; D012559:Schizophrenia / Q000175:diagnosis / Q000473:pathology*; D055815:Young Adult
chemical_list: D002843:Chromatin; D010718:Phosphatidylserines; D053148:Caspase 3
keywords: Antipsychotic-naïve; Apoptosis; Fibroblast culture; First-episode; Schizophrenia; Skin biopsy