ApoE and cholesterol in schizophrenia and bipolar disorder: comparison of grey and white matter and relation with APOE genotype

ApoE and cholesterol in schizophrenia and bipolar disorder: comparison of grey and white matter and relation with APOE genotype

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J Psychiatry Neurosci 2011;36(1):47-55

Fidel Vila-Rodriguez, MD; William G. Honer, MD; Sheila M. Innis, PhD; Cheryl L. Wellington, PhD; Clare L. Beasley, PhD

Vila-Rodriguez, Honer, Beasley — Department of Psychiatry; Innis — Department of Pediatrics; Wellington — Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC

Abstract

Background: Apolipoprotein E (apoE) and cholesterol play a critical role in synapse and myelin maintenance and integrity and are thus appealing candidates in the pathogenesis of schizophrenia and bipolar disorder. To explore the role of these 2 molecules, we quantified cholesterol and apoE levels in prefrontal grey and white matter in patients with schizophrenia, bipolar disorder and healthy controls. Furthermore, we investigated the relations between apoE and cholesterol levels and the APOE genotype.

Methods: We obtained dorsolateral prefrontal grey and white matter from the Stanley Medical Research Institute Brain Collection (schizophrenia n = 35, bipolar disorder n = 35 and controls n = 35). Cholesterol levels were quantified using high-pressure liquid chromatography, whereas apoE was measured by enzyme-linked immunosorbent assay.

Results: We found no significant differences in cholesterol or apoE levels among the groups. ApoE levels were higher in grey matter than in white matter in all groups; conversely, levels of cholesterol were higher in white matter than in grey matter. We observed a significant inverse correlation between apoE and cholesterol levels in both grey and white matter. Furthermore, in grey matter, apoE levels were significantly higher in APOE ε2 carriers compared with APOE ε3 or APOE ε4 carriers, with cholesterol levels following the opposite trend.

Limitations: Limitations of our study include our inability to control for poten tial confounding variables and the small numbers of APOE ε2 and ε4 carriers in each group.

Conclusion: Although large amounts of cholesterol are present in white matter, apoE expression is limited. The APOE genotype may play a role in the regulation of both cholesterol and apoE levels in grey matter. The impact of APOE polymorphisms on lipid homeostasis in people with psychiatric disorders warrants further investigation.


Submitted Sept. 14, 2009; Revised Apr. 29, 2010; Accepted May 31, 2010.

Acknowledgments: Postmortem brain tissue was donated by The Stanley Medical Research Institute’s brain collection. We would like to acknowledge Jennifer Chan for technical assistance. Funding for this study was provided by a BC Mental Health and Addiction Services Clinical Research Fellowship (to Dr. Vila-Rodriguez), BC Mental Health and Addiction Services, Michael Smith Foundation for Health Research, Canadian Institutes of Health Research (MOP-14037, NET-54013, MOP-81112) and the Stanley Medical Research Institute (to Drs. Honer and Beasley).

Competing interests: None declared for Drs. Vila-Rodriguez, Innis and Wellington. Dr. Honer is a paid board member of the Alberta Heritage Medical Research Foundation, Janssen, Novartis and AstraZeneca and a voluntary board member of In Silico Biosciences; he has received or will receive grants from Janssen, Eli Lilly and AstraZeneca; he has received honoraria from Partners in Psychiatry, Hotel Dieu Hospital (Kingston), Rush University, the Capital Mental Health Association (Victoria), Université de Montréal, Janssen and AstraZeneca. Dr. Beasley declared having received an honorarium from the Ontraio Mental Health Foundation and a Winter Conference on Brain Research travel fellowship.

Contributors: Drs. Vila-Rodriguez, Honer and Beasley designed the study. Drs. Vila-Rodriguez, Innis, Wellington and Beasley acquired the data, which Drs. Vila-Rodriguez, Honer and Beasley analyzed. Drs. Vila-Rodriguez and Beasley wrote the article, which Drs. Vila-Rodriguez, Honer, Innis and Wellington reviewed. All authors approved the article’s publication.

DOI: 10.1503/jpn.090116

Correspondence to: Dr. C.L. Beasley, BC Mental Health and Addictions Research Institute, A3 115-938 West 28th Ave., Vancouver BC V5Z 4H4; cbeasley@interchange.ubc.ca