title: Evidence of aberrant DNA damage response signalling but normal rates of DNA repair in dividing lymphoblasts from patients with schizophrenia.
abstract: OBJECTIVE
  Cancer incidence in schizophrenia is not increased commensurate with higher rates of risk exposures. Here we report an investigation of the DNA damage response, an anti-tumorigenic defence, in immortalised lymphoblasts from patients with schizophrenia.
  
  
  METHODS
  Unirradiated and irradiated (5Gy) lymphoblasts from schizophrenia patients (n = 28) and healthy controls (n = 28) were immunostained for the phosphorylated histone variant H2AX (γH2AX), an index of DNA double-strand breaks. Flow cytometry was used to assess cell cycle distribution and γH2AX immunofluorescence. Rate of DNA repair was quantified by determining the temporal change in γH2AX values following irradiation.
  
  
  RESULTS
  In unirradiated lymphoblasts, γH2AX levels were significantly increased in the schizophrenia group compared with controls (effect size = 0.86). This increase was most evident in patients with cognitive deficits. In irradiated lymphoblasts, peak radiation-induced γH2AX levels were significantly reduced in patients. No differences between patients and controls were found in the rate of DNA repair or in cell cycle distribution.
  
  
  CONCLUSIONS
  The significant differences in DNA damage response signalling observed involve modification of histone variant H2AX and thereby implicate regulatory processes determining chromatin structure in dividing lymphoblasts from patients with schizophrenia. The role that aberrant DNA damage response signalling plays in protecting patients from cancer is unclear.
authors.affiliation: Schizophrenia Research Institute, Darlinghurst, NSW, Australia. v.catts@NeuRA.edu.au
authors.forename: Vibeke Sørensen
authors.initials: VS
authors.lastname: Catts
authors.forename: Stanley Victor
authors.initials: SV
authors.lastname: Catts
authors.forename: Assen
authors.initials: A
authors.lastname: Jablensky
authors.forename: David
authors.initials: D
authors.lastname: Chandler
authors.forename: Cynthia Shannon
authors.initials: CS
authors.lastname: Weickert
authors.forename: Martin F
authors.initials: MF
authors.lastname: Lavin
mesh_terms: D000328:Adult; D015415:Biomarkers; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D002843:Chromatin / Q000737:chemistry; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects*; D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair; D005434:Flow Cytometry; D006657:Histones / Q000528:radiation effects*; D006801:Humans; D008214:Lymphocytes / Q000166:cytology* / Q000528:radiation effects; D008297:Male; D012559:Schizophrenia / Q000235:genetics / Q000503:physiopathology*
chemical_list: D015415:Biomarkers; D002843:Chromatin; C468783:H2AX protein, human; D006657:Histones