Evidence for oxidative DNA damage in the hippocampus of elderly patients with chronic schizophrenia.
OBJECTIVE
The authors investigated the idea that some patients with schizophrenia exhibit a chronic, deteriorating course without showing frank neurodegeneration at postmortem examination. Oxidative damage is one form of cellular injury that may cause cellular dysfunction without necessarily leading to neuron death.


METHODS
Authors obtained postmortem hippocampi from 13 elderly non-psychiatric comparison cases and 10 patients with "poor-outcome" schizophrenia. The groups were compared for the presence of neuronal 8-hydroxy, 2' deoxyguanosine (8-OHdG), a robust marker of oxidized DNA, and neuronal Ki-67, a marker of cell-cycle activation, as well as neurofibrillary tangles, amyloid-beta senile plaques, and astrocytosis.


RESULTS
The mean proportion of neurons exhibiting 8-OHdG immunoreactivity was 10 times higher in schizophrenia than in comparison cases. Ki-67 was similarly elevated and was correlated with 8-OHdG in the schizophrenia group. There were no significant between-group differences for densities of neurofibrillary tangles, amyloid-beta plaques, or astrocytes.


CONCLUSIONS
Our data provide evidence for oxidative DNA damage and coordinated cell-cycle activation in elderly "poor-outcome" schizophrenia. These findings could have important implications for cellular metabolism, gene expression, and membrane functioning in schizophrenia.
Nishioka
Naoya
N
Cellular and Molecular Neuropathology Program, Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA.
Arnold
Steven E
SE
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000235:genetics; D014150:Antipsychotic Agents / Q000627:therapeutic use; D018797:Cell Cycle Proteins / Q000235:genetics; D002908:Chronic Disease; D003072:Cognition Disorders / Q000175:diagnosis / Q000235:genetics; D003849:Deoxyguanosine / Q000235:genetics; D005260:Female; D006624:Hippocampus / Q000503:physiopathology*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000235:genetics; D008297:Male; D009483:Neuropsychological Tests; D018384:Oxidative Stress / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology*
D000906:Antibodies; D014150:Antipsychotic Agents; D018797:Cell Cycle Proteins; D019394:Ki-67 Antigen; C051607:8-hydroxyadenosine 5'-triphosphate; D000255:Adenosine Triphosphate; D003849:Deoxyguanosine