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 apoptos is and also exerts neurotrophic activity in the central nervous system (CNS ), Bcl-2 expression is increased in the CNS of several neurodegenerarive di sorders. Given that schizophrenia has certain features of a limited neurode generative disorder, it was hypothesized that cortical Bcl-2 expression is increased in schizophrenia Methods: Postmortem temporal cortex was obtained from the Stanley Foundatio n Neuropathology Consortium with matched control, schizophrenic, bipolar, a nd depressed subjects, Bcl-2 protein was measured by enzyme-linked immunoas say (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 schizop hrenic and bipolar subjects revealed twofold higher mean Bcl-2 in antipsych otic-treated versus neuroleptic-naive subjects. Conclusions: Contrary to our hypothesis, cortical Bcl-2 was reduced in schi zophrenia. This supports the notion that schizophrenia is not a classic neu rodegenerative disorder; however, less Bcl-2 protein may signal neuronal vu lnerability to proapoptotic stimuli and to neuronal atrophy. Also, the asso ciation between neuroleptic exposure and higher Bcl-2 levels could underlie the favorable long-term outcomes of patients who receive maintenance antip sychotic treatment. (C) 2000 Society of Biological Psychiatry.