Polymorphisms in genes implicated in dopamine, serotonin and noradrenalin metabolism suggest association with cerebrospinal fluid monoamine metabolite concentrations in psychosis

摘要: Homovanillic acid (HVA), 5-hydroxyindoleacetic (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) are the major monoamine metabolites in central nervous system (CNS). Their cerebrospinal fluid (CSF) concentrations, reflecting turnover rates CNS, partially under genetic influence have been associated with schizophrenia. We hypothesized that CSF metabolite concentrations represent intermediate steps between single nucleotide polymorphisms (SNPs) genes implicated monoaminergic pathways psychosis. searched for association 119 SNPs [tryptophan hydroxylase 1 (TPH1), TPH2, tyrosine (TH), DOPA decarboxylase (DDC), dopamine beta-hydroxylase (DBH), catechol-O-methyltransferase (COMT), oxidase A (MAOA) MAOB] 74 patients psychotic disorder. There were 42 nominally significant associations which exceeded expected number (20) of nominal given total tests performed. The strongest (p = 0.0004) was found MAOB rs5905512, a SNP previously reported to be schizophrenia men, MHPG men Further analyses 111 healthy individuals revealed 41 restricted psychosis absent controls. present study suggests altered CNS reflect