title: Central nervous system serotonin and clustering of hostility, psychosocial, metabolic, and cardiovascular endophenotypes in men.
abstract: To use measures of cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5HIAA) and genotype of a functional polymorphism of the monoamine oxidase A gene promoter (MAOA-uVNTR) to study the role of central nervous system (CNS) serotonin in clustering of hostility, other psychosocial, metabolic and cardiovascular endophenotypes.
  
  
  
  In 86 healthy male volunteers, we evaluated CSF levels of the primary serotonin metabolite 5HIAA and MAOA-uVNTR genotype for association with a panel of 29 variables assessing hostility, other psychosocial, metabolic, and cardiovascular endophenotypes.
  
  
  
  The correlations of 5HIAA with these endophenotypes in men with more active MAOA-uVNTR alleles were significantly different from those of men with less active alleles for 15 of the 29 endophenotypes. MAOA-uVNTR genotype and CSF 5HIAA interacted to explain 20% and 22% of the variance, respectively, in scores on one factor wherein high scores reflected a less healthy psychosocial profile and a second factor wherein high score reflected increased insulin resistance, body mass index, blood pressure and hostility. In men with less active alleles, higher 5HIAA was associated with more favorable profiles of hostility, other psychosocial, metabolic and cardiovascular endophenotypes; in men with more active alleles, higher 5HIAA was associated with less favorable profiles.
  
  
  
  These findings indicate that, in men, indices of CNS serotonin function influence the expression and clustering of hostility, other psychosocial, metabolic and cardiovascular endophenotypes that have been shown to increase risk of developing cardiovascular disease. The findings are consistent with the hypothesis that increased CNS serotonin is associated with a more favorable psychosocial/metabolic/cardiovascular profile, whereas decreased CNS serotonin function is associated with a less favorable profile.
authors.affiliation: Department of Psychiatry, Duke University Medical Center, Durham, NC 27710, USA. redfordw@duke.edu
authors.forename: Redford B
authors.initials: RB
authors.lastname: Williams
authors.forename: Richard S
authors.initials: RS
authors.lastname: Surwit
authors.forename: Ilene C
authors.initials: IC
authors.lastname: Siegler
authors.forename: Allison E
authors.initials: AE
authors.lastname: Ashley-Koch
authors.forename: Ann L
authors.initials: AL
authors.lastname: Collins
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Helms
authors.forename: Anastasia
authors.initials: A
authors.lastname: Georgiades
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Boyle
authors.forename: Beverly H
authors.initials: BH
authors.lastname: Brummett
authors.forename: John C
authors.initials: JC
authors.lastname: Barefoot
authors.forename: Katherine
authors.initials: K
authors.lastname: Grichnik
authors.forename: Mark
authors.initials: M
authors.lastname: Stafford-Smith
authors.forename: Edward C
authors.initials: EC
authors.lastname: Suarez
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Kuhn
mesh_terms: D000328:Adult; D000483:Alleles; D002490:Central Nervous System / Q000378:metabolism*; D016000:Cluster Analysis; D003327:Coronary Disease / Q000453:epidemiology / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005838:Genotype; D006791:Hostility; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid* / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics* / Q000378:metabolism; D008995:Monoamine Oxidase / Q000134:cerebrospinal fluid* / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors; D012701:Serotonin / Q000235:genetics* / Q000378:metabolism*
chemical_list: D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D008995:Monoamine Oxidase