Implications of lipid biology for the pathogenesis of schizophrenia

Berger, Gregor E., Wood, Stephen J., Pantelis, Christos, Velakoulis, Dennis, Wellard, R. Mark, & Mcgorry, Patrick D. (2002) Implications of lipid biology for the pathogenesis of schizophrenia. Australian and New Zealand Journal of Psychiatry, 36(3), pp. 355-366.

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Objective: Preclinical and clinical data suggest that lipid biology is integral to brain development and neurodegeneration. Both aspects are proposed as being important in the pathogenesis of schizophrenia. The purpose of this paper is to examine the implications of lipid biology, in particular the role of essential fatty acids (EFA), for schizophrenia.

Methods: Medline databases were searched from 1966 to 2001 followed by the crosschecking of references.

Results: Most studies investigating lipids in schizophrenia described reduced EFA, altered glycerophospholipids and an increased activity of a calcium-independent phospholipase A2 in blood cells and in post-mortem brain tissue. Additionally, in vivo brain phosphorus-31 Magnetic Resonance Spectroscopy (31P-MRS) demonstrated lower phosphomonoesters (implying reduced membrane precursors) in first- and multi-episode patients. In contrast, phosphodiesters were elevated mainly in first-episode patients (implying increased membrane breakdown products), whereas inconclusive results were found in chronic patients. EFA supplementation trials in chronic patient populations with residual symptoms have demonstrated conflicting results. More consistent results were observed in the early and symptomatic stages of illness, especially if EFA with a high proportion of eicosapentaenoic acid was used.

Conclusion: Peripheral blood cell, brain necropsy and 31P-MRS analysis reveal a disturbed lipid biology, suggesting generalized membrane alterations in schizophrenia. 31P-MRS data suggest increased membrane turnover at illness onset and persisting membrane abnormalities in established schizophrenia. Cellular processes regulating membrane lipid metabolism are potential new targets for antipsychotic drugs and might explain the mechanism of action of treatments such as eicosapentaenoic acid.

Impact and interest:

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ID Code: 51346
Item Type: Journal Article
Refereed: Yes
Keywords: essential fatty acids, magnetic resonance spectroscopy, niacinphospholipases, phospholipids
DOI: 10.1046/j.1440-1614.2001.01021.x
ISSN: 1440-1614
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > BIOCHEMISTRY AND CELL BIOLOGY (060100) > Cell Neurochemistry (060105)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > CLINICAL SCIENCES (110300) > Psychiatry (incl. Psychotherapy) (110319)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > CLINICAL SCIENCES (110300) > Radiology and Organ Imaging (110320)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > NEUROSCIENCES (110900) > Central Nervous System (110903)
Divisions: Current > Schools > School of Chemistry, Physics & Mechanical Engineering
Current > Institutes > Institute of Health and Biomedical Innovation
Current > QUT Faculties and Divisions > Science & Engineering Faculty
Deposited On: 04 Jul 2012 00:43
Last Modified: 04 Jul 2012 00:43

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