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Cerebrospinal fluid monoamine metabolite concentrations as intermediate phenotypes between glutamate-related genes and psychosis
Karolinska Hosp & Inst, Dept Clin Neurosci, Psychiat Sect, HUBIN Project, Stockholm, Sweden..
Karolinska Hosp & Inst, Dept Clin Neurosci, Psychiat Sect, HUBIN Project, Stockholm, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
Karolinska Hosp & Inst, Dept Clin Neurosci, Psychiat Sect, HUBIN Project, Stockholm, Sweden..
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2015 (English)In: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 229, no 1-2, 497-504 p.Article in journal (Refereed) Published
Abstract [en]

Glutamate-related genes have been associated with schizophrenia, but the results have been ambiguous and difficult to replicate. Homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) are the major degradation products of the monoamines dopamine, serotonin and noradrenaline, respectively, and their concentrations in the cerebrospinal fluid (CSF), mainly HVA, have been associated with schizophrenia. In the present study, we hypothesized that CSF HVA, 5-HIAA and MHPG concentrations represent intermediate phenotypes in the association between glutamate-related genes and psychosis. To test this hypothesis, we searched for association between 238 single nucleotide polymorphisms (SNPs) in ten genes shown to be directly or indirectly implicated in glutamate transmission and CSF HVA, 5-HIAA and MHPG concentrations in 74 patients with psychotic disease. Thirty-eight nominally significant associations were found. Further analyses in 111 healthy controls showed that 87% of the nominal associations were restricted to the patients with psychosis. Some of the psychosis-only-associated SNPs found in the D-amino acid oxidase activator (DADA) and the kynurenine 3-monooxygenase (KMO) genes have previously been reported to be associated with schizophrenia. The present results suggest that CSF monoamine metabolite concentrations may represent intermediate phenotypes in the association between glutamate-related genes and psychosis.

Place, publisher, year, edition, pages
2015. Vol. 229, no 1-2, 497-504 p.
Keyword [en]
Schizophrenia, Psychiatric genetics, Homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), 3-methoxy-4-hydroxyphenylglycol (MHPG)
National Category
Psychiatry
Identifiers
URN: urn:nbn:se:uu:diva-264038DOI: 10.1016/j.psychres.2015.06.023ISI: 000360772600071PubMedID: 26142836OAI: oai:DiVA.org:uu-264038DiVA: diva2:859279
Funder
Swedish Research Council, K2007-62X-15077-04-1 K2008-62P-20597-01-3. K2010-62X-15078-07-2 K2012-61X-15078-09-3Stockholm County CouncilKnut and Alice Wallenberg Foundation
Available from: 2015-10-06 Created: 2015-10-05 Last updated: 2017-12-01Bibliographically approved

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