title: Polymorphisms in genes implicated in dopamine, serotonin and noradrenalin metabolism suggest association with cerebrospinal fluid monoamine metabolite concentrations in psychosis.
abstract: BACKGROUND
  Homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) are the major monoamine metabolites in the central nervous system (CNS). Their cerebrospinal fluid (CSF) concentrations, reflecting the monoamine turnover rates in CNS, are partially under genetic influence and have been associated with schizophrenia. We have hypothesized that CSF monoamine metabolite concentrations represent intermediate steps between single nucleotide polymorphisms (SNPs) in genes implicated in monoaminergic pathways and psychosis.
  
  
  METHODS
  We have searched for association between 119 SNPs in genes implicated in monoaminergic pathways [tryptophan hydroxylase 1 (TPH1), TPH2, tyrosine hydroxylase (TH), DOPA decarboxylase (DDC), dopamine beta-hydroxylase (DBH), catechol-O-methyltransferase (COMT), monoamine oxidase A (MAOA) and MAOB] and monoamine metabolite concentrations in CSF in 74 patients with psychotic disorder.
  
  
  RESULTS
  There were 42 nominally significant associations between SNPs and CSF monoamine metabolite concentrations, which exceeded the expected number (20) of nominal associations given the total number of tests performed. The strongest association (p = 0.0004) was found between MAOB rs5905512, a SNP previously reported to be associated with schizophrenia in men, and MHPG concentrations in men with psychotic disorder. Further analyses in 111 healthy individuals revealed that 41 of the 42 nominal associations were restricted to patients with psychosis and were absent in healthy controls.
  
  
  CONCLUSIONS
  The present study suggests that altered monoamine turnover rates in CNS reflect intermediate steps in the associations between SNPs and psychosis.
authors: Department of Clinical Neuroscience, Psychiatry Section, HUBIN Project, Karolinska Institutet and Hospital, R5:00, SE-171 76 Stockholm, Sweden. dimitrios.andreou@sll.se.
authors: Dimitrios
authors: D
authors: Andreou
authors: Erik
authors: E
authors: Söderman
authors: Tomas
authors: T
authors: Axelsson
authors: Göran C
authors: GC
authors: Sedvall
authors: Lars
authors: L
authors: Terenius
authors: Ingrid
authors: I
authors: Agartz
authors: Erik G
authors: EG
authors: Jönsson
mesh_terms: D000328:Adult; D015306:Biogenic Monoamines / Q000134:cerebrospinal fluid; D004298:Dopamine / Q000134:cerebrospinal fluid*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000134:cerebrospinal fluid*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011618:Psychotic Disorders / Q000134:cerebrospinal fluid* / Q000235:genetics*; D012701:Serotonin / Q000134:cerebrospinal fluid*
chemical_list: D015306:Biogenic Monoamines; D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine