Elevated PLA2 activity in schizophrenics and other psychiatric patients

Noponen, Mikla; Sanfilipo, Michael; Samanich, Karen M.; Ryer, Helena I.; Ko, Grant N.; Angrist, Burt; Wolkin, Adam; Duncan, Erica; Rotrosen, John

doi:10.1016/0006-3223(93)90157-9

Cited by 135 publications

(65 citation statements)

References 28 publications

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“…Noponen et al [73] found increased serum PLA 2 levels in schizophrenia patients and psychiatric controls. Several studies suggest that this PLA 2 overactivity is calcium independent [74][75][76].…”

Section: Pla 2 Activity In Psychosesmentioning

confidence: 95%

Psychoses and creativity: is the missing link a biological mechanism related to phospholipids turnover?

Folley

Doop

Park

2003

Prostaglandins, Leukotrienes and Essential Fatty Acids

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Recent evidence suggests that genetic and biochemical factors associated with psychoses may also provide an increased propensity to think creatively. The evolutionary theories linking brain growth and diet to the appearance of creative endeavors have been made recently, but they lack a direct link to research on the biological correlates of divergent and creative thought. Expanding upon Horrobin's theory that changes in brain size and in neural microconnectivity came about as a result of changes in dietary fat and phospholipid incorporation of highly unsaturated fatty acids, we propose a theory relating phospholipase A 2 (PLA 2 ) activity to the neuromodulatory effects of the noradrenergic system. This theory offers probable links between attention, divergent thinking, and arousal through a mechanism that emphasizes optimal individual functioning of the PLA 2 and NE systems as they interact with structural and biochemical states of the brain. We hope that this theory will stimulate new research in the neural basis of creativity and its connection to psychoses.

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Section: Pla 2 Activity In Psychosesmentioning

confidence: 95%

Psychoses and creativity: is the missing link a biological mechanism related to phospholipids turnover?

Folley

Doop

Park

2003

Prostaglandins, Leukotrienes and Essential Fatty Acids

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“…A small case-control study showed that serum PLA 2 activity was increased in patients with bipolar disorder, 96 and genetic mapping studies have demonstrated an alteration in the sPLA 2 gene of bipolar disorder patients. 97,98 However, another study did not detect a difference in the BanI cPLA 2 and AvrII iPLA 2 polymorphisms, and in the sPLA 2 ATT repeat, between bipolar disorder patients and controls.…”

Section: Observations Related To Aa In Bipolar Disorder Patientsmentioning

confidence: 99%

Mode of action of mood stabilizers: is the arachidonic acid cascade a common target?

et al. 2008

Mol Psychiatry

109

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Bipolar disorder is a major medical, social and economic burden worldwide. However, the mechanisms of action of effective antibipolar disorder drugs remain elusive. In this paper, we review studies using a neuropharmacological approach in unanesthetized rats, combined with kinetic, biochemical and molecular biology techniques, showing that chronic administration of three Food and Drug Administration-approved mood stabilizers (lithium, valproate and carbamazepine) at therapeutically relevant doses, selectively target the brain arachidonic acid (AA) cascade. Whereas chronic lithium and carbamazepine decrease the binding activity of activator protein-2 and in turn the transcription, translation and activity of its AA-selective calcium-dependent phospholipase A 2 gene product, valproate appears to be a non-competitive inhibitor of long-chain acyl-CoA synthetase. The net overlapping effects of the three drugs are decreased turnover of AA but not of docosahexaenoic acid in rat brain phospholipids, and decreased brain cyclooxygenase-2 and prostaglandin E 2 . Although these observations support the hypothesis proposed by Rapoport and colleagues that the AA cascade is a common target of mood stabilizers, this hypothesis is not necessarily exclusive of other targets. Targeting the AA cascade with drugs or diet may be a useful therapeutic approach in bipolar disorder, and examining the AA cascade in patients might help in better understanding the disease.

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“…72 Additionally, a recent study has reported on a direct measure of the PLA2G4A protein, and found increased levels of PLA2G4A in schizophrenia. 73 The method used by Noponen et al 74 to detect increased PLA2 activity was novel, with the target PLA2s unconfirmed, and thus will be excluded from further discussion. Owing to the limitations in methodology activity studies will be examined in terms of PLA2 calcium requirements.…”

Section: Direct Evidence Of Altered Pla2 Activity In Schizophreniamentioning

confidence: 99%

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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Elevated PLA2 activity in schizophrenics and other psychiatric patients

Cited by 135 publications

References 28 publications

Psychoses and creativity: is the missing link a biological mechanism related to phospholipids turnover?

Psychoses and creativity: is the missing link a biological mechanism related to phospholipids turnover?

Mode of action of mood stabilizers: is the arachidonic acid cascade a common target?

The role of phospholipases A2 in schizophrenia

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