Cortical Bcl-2 protein expression and apoptotic regulation in schizophrenia

• Published in: Biological psychiatry (1969) Vol. 48; no. 7; pp. 641 - 650
• Main Authors: Jarskog, L.Fredrik, Gilmore, John H, Selinger, Elzbieta S, Lieberman, Jeffrey A
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.10.2000; Elsevier Science
• Subjects: Adult; Adult and adolescent clinical studies; apoptosis; Apoptosis - physiology; Bcl-2; Biological and medical sciences; Bipolar Disorder - pathology; Blotting, Western; Depressive Disorder, Major - pathology; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Medical sciences; Middle Aged; neurodegeneration; neurodevelopment; neuroprotection; Proto-Oncogene Proteins c-bcl-2 - analysis; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Reference Values; Schizophrenia; Schizophrenia - pathology; Temporal Lobe - pathology; Bcl-2; neurodegeneration; apoptosis; schizophrenia; neurodevelopment; neuroprotection; Human; Cerebral cortex; Neuroleptic; Pathogenesis; Central nervous system; Schizophrenia; Temporal cortex; Gene expression; Psychosis; Chemotherapy; Antipsychotic; Brain (vertebrata); Apoptosis
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/S0006-3223(00)00988-4

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.