Cortical bcl-2 protein expression and apoptotic regulation in schizophrenia.
BACKGROUND
The etiology of schizophrenia remains unknown; however, a role for apoptosis has been hypothesized. Bcl-2 is a potent inhibitor of apoptosis and also exerts neurotrophic activity in the central nervous system (CNS). Bcl-2 expression is increased in the CNS of several neurodegenerative disorders. Given that schizophrenia has certain features of a limited neurodegenerative disorder, it was hypothesized that cortical Bcl-2 expression is increased in schizophrenia.


METHODS
Postmortem temporal cortex was obtained from the Stanley Foundation Neuropathology Consortium with matched control, schizophrenic, bipolar, and depressed subjects. Bcl-2 protein was measured by enzyme-linked immunoassay (ELISA) and Western blot. Primary analysis was limited to schizophrenia versus control subjects.


RESULTS
The ELISA demonstrated 25% less Bcl-2 protein in schizophrenia (p =.046), supported by Western blot results. A secondary analysis of schizophrenic and bipolar subjects revealed twofold higher mean Bcl-2 in antipsychotic-treated versus neuroleptic-naive subjects.


CONCLUSIONS
Contrary to our hypothesis, cortical Bcl-2 was reduced in schizophrenia. This supports the notion that schizophrenia is not a classic neurodegenerative disorder; however, less Bcl-2 protein may signal neuronal vulnerability to proapoptotic stimuli and to neuronal atrophy. Also, the association between neuroleptic exposure and higher Bcl-2 levels could underlie the favorable long-term outcomes of patients who receive maintenance antipsychotic treatment.
Jarskog
L F
LF
Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA.
Gilmore
J H
JH
Selinger
E S
ES
Lieberman
J A
JA
D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D001714:Bipolar Disorder / Q000473:pathology; D015153:Blotting, Western; D003865:Major Depressive Disorder / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D012016:Reference Values; D012559:Schizophrenia / Q000473:pathology*; D013702:Temporal Lobe / Q000473:pathology*
D019253:Proto-Oncogene Proteins c-bcl-2