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The role of phospholipases A2 in schizophrenia

Molecular Psychiatry volume 11, pages 547–556 (2006)Cite this article

Abstract

A range of neurotransmitter systems have been implicated in the pathogenesis of schizophrenia based on the antidopaminergic activities of antipsychotic medications, and chemicals that can induce psychotic-like symptoms, such as ketamine or PCP. Such neurotransmitter systems often mediate their cellular response via G-protein-coupled release of arachidonic acid (AA) via the activation of phospholipases A2 (PLA2s). The interaction of three PLA2s are important for the regulation of the release of AA – phospholipase A2 Group 2 A, phospholipase A2 Group 4A and phospholipase A2 Group 6A. Gene variations of these three key enzymes have been associated with schizophrenia with conflicting results. Preclinical data suggest that the activity of these three enzymes are associated with monoaminergic neurotransmission, and may contribute to the differential efficacy of antipsychotic medications, as well as other biological changes thought to underlie schizophrenia, such as altered neurodevelopment and synaptic remodelling. We review the evidence and discuss the potential roles of these three key enzymes for schizophrenia with particular emphasis on published association studies.

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Abbreviations

AA:

arachidonic acid

AMPAR:

glutamate receptor

BanI :

PLA2G4A, rs10798059, intron one adenine/guanine variant

bp:

DNA base pairs

CDCV:

common disease common variant

CDRV:

common disease rare variant

CNS:

central nervous system

EFA:

essential fatty acids

G-proteins:

guanosine triphosphate binding proteins

GWL:

genomewide linkage studies

LD:

linkage disequilibrium

LTP:

long-term potentiation

mRNA:

messenger RNA

PLA2:

phospholipase A2

PLA2GIVA, PLA2G4A:

phospholipase A2 Group 4 A

PLA2GIIA, PLA2G2A:

phospholipase A2 Group 2 A

PLA2GVIA, PLA2G6A:

phospholipase A2 Group 6 A

Poly(A):

PLA2G4A promotor adenine repeat variant

PUFA:

polyunsaturated fatty acid

31P MRS:

31-phosphorus magnetic resonance imaging

RBC:

red blood cells

TDT:

transmission disequilibrium test

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Acknowledgements

We wish to thank R Purcell for editing and proofreading assistance.

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Authors and Affiliations

  1. Genomic Disorders Research Centre, Melbourne, VI, Australia

    M H Law, R G H Cotton & G E Berger

  2. ORYGEN Research Centre, Melbourne, VI, Australia

    G E Berger

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  1. M H Law
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  2. R G H Cotton
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  3. G E Berger
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Correspondence to G E Berger.

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The URLs for data presented herein is as follows dbSNP, http://www.ncbi.nlm.nih.gov/SNP/

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Law, M., Cotton, R. & Berger, G. The role of phospholipases A2 in schizophrenia. Mol Psychiatry 11, 547–556 (2006). https://doi.org/10.1038/sj.mp.4001819

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