Genetic variant near cytosolic phospholipase A2 associated with schizophrenia

Hudson, Craig J.; Kennedy, James L.; Gotowiec, Andrew; Lin, Anna; King, Nicole; Gojtan, Katherine; Macciardi, Fabìo; Skorecki, Karl; Meltzer, Herbert Y.; Warsh, Jerry J.; Horrobin, David F.

doi:10.1016/0920-9964(96)00031-x

Cited by 72 publications

(43 citation statements)

References 30 publications

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“…20,23 (h) The strengthening of association between schizophrenia and a variant in the PLA2G4A gene after stratification by niacin sensitivity is promising, but not replicated. 90 Yet increased calcium-dependent PLA2 activity, which includes PLA2G4A, was not associated with niacin insensitivity.…”

Section: Discussionmentioning

confidence: 91%

“…Association between schizophrenia and the A7-A10 group was detected under a case/control and a transmission model. 90,91 Additionally, niacin insensitivity was greater in patients with the A7-A10. 91 Later methods detected completely differing alleles, and found association between schizophrenia and Poly(A) ( Tables 3 and 4).…”

Section: Pla2g4amentioning

confidence: 94%

“…87,88 The one reported study of the CA microsatellite found no significant association with schizophrenia (Table 4). 89 Hudson et al 90,91 reported the PLA2G4A promotor adenine repeat variant (Poly(A)) (an adenine repeat) occurred as 10 size alleles, termed A1-A10, ranging from 41 to 60 repeats in length. The small differences between alleles, except for five bases between A6 and A7 made genotyping difficult, so analysis was performed using A1-A6 vs A7-A10 groupings.…”

Section: Pla2g4amentioning

confidence: 99%

“…101 Although studies have used alternative PLA2s, such as PLA2G1B, there are no published association studies of PLA2G2A in psychotic illnesses. 90,92,101 …”

Section: Pla2g2a and Pla2g6amentioning

confidence: 99%

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The role of phospholipases A2 in schizophrenia

Law¹,

Cotton²,

Berger

2006

Mol Psychiatry

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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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Section: Discussionmentioning

confidence: 91%

Section: Pla2g4amentioning

confidence: 94%

Section: Pla2g4amentioning

confidence: 99%

“…101 Although studies have used alternative PLA2s, such as PLA2G1B, there are no published association studies of PLA2G2A in psychotic illnesses. 90,92,101 …”

Section: Pla2g2a and Pla2g6amentioning

confidence: 99%

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The role of phospholipases A2 in schizophrenia

Law¹,

Cotton²,

Berger

2006

Mol Psychiatry

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“…Presentation of free AA to COX is accomplished by the action of PLA 2 , which may be abnormally active in niacinsubsensitive SZ (Hudson et al, 1996;Tavares et al, 2003). Any process leading to diminished output of prostaglandins could potentially account for niacin subsensitivity.…”

Section: Possible Mechanisms For the Niacin Response Abnormality In Szmentioning

confidence: 99%

Phospholipid, arachidonate and eicosanoid signaling in schizophrenia

Messamore

Yao

2015

OCL

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-This paper reviews the potential role of arachidonic acid in the pathophysiology of schizophrenia. We discuss how abnormal levels of arachidonic acid may arise, and how dysregulation of signaling molecules derived from it have the potential to disrupt not only dopamine signaling, but numerous other physiological processes associated with the illness. Pharmacological doses of niacin stimulate the release of arachidonic acid; and arachidonic acid-derived molecules in turn dilate blood vessels in the skin. A blunted skin flush response to niacin is reliably observed among patients with schizophrenia. The niacin response abnormality may thus serve as a biomarker to identify a physiological subtype of schizophrenia associated with defective arachidonic acid-derived signaling.Keywords: Phospholipids / arachidonic acid / eicosanoids / niacin-induced flushing, endophenotype marker / schizophrenia Résumé -Signalisation des phospholipides, de l'arachidonate et de l'écosanoïde dans la schizophrénie. Cet article examine le rôle potentiel de l'acide arachidonique dans la physiopathologie de la schizophrénie. Il est discuté comment des niveaux anormaux d'acide arachidonique peuvent survenir, et comment la dérégulation des molécules de signalisation qui en découle est capable de perturber non seulement la signalisation de la dopamine, mais aussi de nombreux autres processus physiologiques associés avec cette maladie. Des doses pharmacologiques de niacine stimulent la libération d'acide arachidonique ; des molécules dérivées de l'acide arachidonique dilatent à leur tour les vaisseaux sanguins dans la peau. Une brusque rougeur de la peau en réponse à la niacine est observée de manière constante parmi les patients atteints de schizophrénie. La réponse anormale à la niacine peut donc servir de biomarqueur afin d'identifier un sous-type physiologique de la schizophrénie, associé à un système défectueux de signalisation des dérivés de l'acide arachidonique.

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