The niacin challenge test: Clinical manifestation of altered transmembrane signal transduction in schizophrenia?

Hudson, Craig J.; Lin, Anna; Cogan, Samantha; Cashman, Frank E.; Warsh, Jerry J.

doi:10.1016/s0006-3223(96)00112-6

Cited by 69 publications

(45 citation statements)

References 21 publications

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“…The topical Niacin skin flush test or RBC AA level measurements have the potential to identify such an endophenotype. 45,61,64,115,116 As reported, these three PLA2 enzymes lie downstream of activation of neurotransmitter pathways implicated in schizophrenia, such as dopaminergic, serotoninergic or glutamatergic systems. It is plausible that antipsychotic efficacy can be modulated by PLA2 genetic variants.…”

Section: Resultsmentioning

confidence: 78%

“…60 Depending on the method/definitions used, 40-80% of patients with psychotic disorders and 10% of controls show an impaired sensitivity to niacin. [61][62][63][64] Niacin sensitivity is also impaired in healthy first degree relatives of probands, suggesting it is a marker for underlying genetic risk. 65 Niacin insensitivity remains associated with schizophrenia after exclusion of environmental factors modifying inflammation.…”

Section: Pla2s and Reduced Pufas In Schizophreniamentioning

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: Resultsmentioning

confidence: 78%

Section: Pla2s and Reduced Pufas In Schizophreniamentioning

confidence: 99%

The role of phospholipases A2 in schizophrenia

Law¹,

Cotton²,

Berger

2006

Mol Psychiatry

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“…Impaired niacin-induced flushing has been associated with greater severity of both positive and negative symptoms of SZ (Berger et al, 2002;Glen et al, 1996;Hudson et al, 1997;Smesny et al, 2003). Niacin response impairment was significantly linked to inorganic phosphate levels revealed by 31 P magnetic resonance spectroscopy (Puri et al, 2007).…”

Section: Clinical Correlates Of Abnormal Niacin Responsementioning

confidence: 99%

“…The niacin skin flush is not affected by local anesthetics, suggesting that local neurotransmitter release is not involved in niacin-induced vasodilatation (Winklemann et al, 1965). There is no correlation between antipsychotic drug dose and niacin sensitivity in patients with SZ (Hudson et al, 1997;Messamore, 2003). Neither has a significant difference in niacin sensitivity been found between medicated versus unmedicated patients (Shah et al, 2000).…”

Section: The Niacin Response Abnormality Is Not An Artifact Of Medicamentioning

confidence: 99%

“…Neither has a significant difference in niacin sensitivity been found between medicated versus unmedicated patients (Shah et al, 2000). In contrast, bipolar disorder patients who take antipsychotic medications have a normal or even enhanced flush response (Hudson et al, 1997) Moreover, niacin subsensitivity occurs in first-degree relatives of schizophrenics, which suggests that this is a heritable trait, independent of medication status (Shah et al, 1999;Waldo, 1999). On the other hand, Tavares et al (2003) reported that 4 out of 13 SZ patients with niacin subsensitivity became sensitive to niacin after 8 weeks of atypical antipsychotic drug treatment.…”

Section: The Niacin Response Abnormality Is Not An Artifact Of Medicamentioning

confidence: 99%

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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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Family‐based and case‐control studies reveal no association oflipocalin‐type prostaglandin D2 synthasewith schizophrenia

Ruano

Macedo²,

Soares³

et al. 2007

American J of Med Genetics Pt B

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Several observations point to the involvement of disturbed lipid biology in schizophrenia. Reduced response to niacin flushing test, which involves vasodilatation induced by prostaglandin D2 (PGD2), is among the evidences, together with decreased CSF levels of lipocalin-type prostaglandin D2 synthase (PTGDS), the enzyme responsible for the synthesis of PGD2 in the brain. Since PTGDS is also a carrier for lipophilic molecules such as retinoids and thyroid hormones, altered PTGDS levels might influence both PGD2-mediated signaling, and vitamin A and thyroid hormone availability. To test whether genetic variants of PTGDS are involved in the etiology of schizophrenia, we searched for variants in the coding and regulatory regions of the gene. We identified four previously described polymorphisms. Using two case-control samples from Portugal and Brazil, none of the polymorphisms tested was associated with the disease. In addition, no transmission distortion was observed in an independent parents-offspring sample from the Azorean Islands. Our data do not support the involvement of the PTGDS gene in the etiology of schizophrenia.

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The niacin challenge test: Clinical manifestation of altered transmembrane signal transduction in schizophrenia?

Cited by 69 publications

References 21 publications

The role of phospholipases A2 in schizophrenia

The role of phospholipases A2 in schizophrenia

Phospholipid, arachidonate and eicosanoid signaling in schizophrenia

Family‐based and case‐control studies reveal no association oflipocalin‐type prostaglandin D2 synthasewith schizophrenia

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