The KMO allele encoding Arg452 is associated with psychotic features in bipolar disorder type 1, and with increased CSF KYNA level and reduced KMO expression
| Autor: | Louise Frisén, Sara K. Olsson, Catharina Lavebratt, Lena Backlund, Pernilla Nikamo, Göran Engberg, Lil Träskman-Bendz, Mikael Landén, Carl M. Sellgren, Urban Ösby, Lutz Priebe, Martin Schalling, Sven Cichon, Marquis P. Vawter, Sophie Erhardt |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Psychosis medicine.medical_specialty Bipolar Disorder Kynurenine pathway Gene Expression Prefrontal Cortex Kynurenic Acid Hippocampus Article Cell Line Young Adult Cellular and Molecular Neuroscience chemistry.chemical_compound Kynurenine 3-Monooxygenase Kynurenic acid kynurenic acid Internal medicine mental disorders Gene expression medicine Humans Genetic Predisposition to Disease psychosis Bipolar disorder Allele Molecular Biology Alleles Aged Psychiatry prefrontal cortex Middle Aged medicine.disease Psychiatry and Mental health Endocrinology Psychotic Disorders chemistry Schizophrenia Case-Control Studies genetic variation gene expression Female Psychology Neuroscience kynurenine pathway |
| Zdroj: | Molecular psychiatry Molecular Psychiatry; 19(3), pp 334-341 (2014) |
| ISSN: | 1476-5578 1359-4184 |
| DOI: | 10.1038/mp.2013.11 |
| Popis: | The kynurenine pathway metabolite kynurenic acid (KYNA), modulating glutamatergic and cholinergic neurotransmission, is increased in cerebrospinal fluid (CSF) of patients with schizophrenia or bipolar disorder type 1 with psychotic features. KYNA production is critically dependent on kynurenine 3-monooxygenase (KMO). KMO mRNA levels and activity in prefrontal cortex (PFC) are reduced in schizophrenia. We hypothesized that KMO expression in PFC would be reduced in bipolar disorder with psychotic features and that a functional genetic variant of KMO would associate with this disease, CSF KYNA level and KMO expression. KMO mRNA levels were reduced in PFC of bipolar disorder patients with lifetime psychotic features (P = 0.005, n = 19) or schizophrenia (P = 0.02, n = 36) compared with nonpsychotic patients and controls. KMO genetic association to psychotic features in bipolar disorder type 1 was studied in 493 patients and 1044 controls from Sweden. The KMO Arg(452) allele was associated with psychotic features during manic episodes (P = 0.003). KMO Arg(452) was studied for association to CSF KYNA levels in an independent sample of 55 Swedish patients, and to KMO expression in 717 lymphoblastoid cell lines and 138 hippocampal biopsies. KMO Arg(452) associated with increased levels of CSF KYNA (P = 0.03) and reduced lymphoblastoid and hippocampal KMO expression (P |
| Databáze: | OpenAIRE |
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