title: Metabolomic profiles in individuals with negative affectivity and social inhibition: a population-based study of Type D personality.
abstract: BACKGROUND
  Individuals with negative affectivity who are inhibited in social situations are characterized as distressed, or Type D, and have an increased risk of cardiovascular disease (CVD). The underlying biomechanisms that link this psychological affect to a pathological state are not well understood. This study applied a metabolomic approach to explore biochemical pathways that may contribute to the Type D personality.
  
  
  METHODS
  Type D personality was determined by the Type D Scale-14. Small molecule biochemicals were measured using two complementary mass-spectrometry based metabolomics platforms. Metabolic profiles of Type D and non-Type D participants within a population-based study in Southern Germany were compared in cross-sectional regression analyses. The PHQ-9 and GAD-7 instruments were also used to assess symptoms of depression and anxiety, respectively, within this metabolomic study.
  
  
  RESULTS
  668 metabolites were identified in the serum of 1502 participants (age 32-77); 386 of these individuals were classified as Type D. While demographic and biomedical characteristics were equally distributed between the groups, a higher level of depression and anxiety was observed in Type D individuals. Significantly lower levels of the tryptophan metabolite kynurenine were associated with Type D (p-value corrected for multiple testing=0.042), while no significant associations could be found for depression and anxiety. A Gaussian graphical model analysis enabled the identification of four potentially interesting metabolite networks that are enriched in metabolites (androsterone sulfate, tyrosine, indoxyl sulfate or caffeine) that associate nominally with Type D personality.
  
  
  CONCLUSIONS
  This study identified novel biochemical pathways associated with Type D personality and demonstrates that the application of metabolomic approaches in population studies can reveal mechanisms that may contribute to psychological health and disease.
authors.affiliation: Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Altmaier
authors.forename: Rebecca T
authors.initials: RT
authors.lastname: Emeny
authors.forename: Jan
authors.initials: J
authors.lastname: Krumsiek
authors.forename: Maria E
authors.initials: ME
authors.lastname: Lacruz
authors.forename: Karoline
authors.initials: K
authors.lastname: Lukaschek
authors.forename: Sibylle
authors.initials: S
authors.lastname: Häfner
authors.forename: Gabi
authors.initials: G
authors.lastname: Kastenmüller
authors.forename: Werner
authors.initials: W
authors.lastname: Römisch-Margl
authors.forename: Cornelia
authors.initials: C
authors.lastname: Prehn
authors.forename: Robert P
authors.initials: RP
authors.lastname: Mohney
authors.forename: Anne M
authors.initials: AM
authors.lastname: Evans
authors.forename: Michael V
authors.initials: MV
authors.lastname: Milburn
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Jerzy
authors.initials: J
authors.lastname: Adamski
authors.forename: Fabian
authors.initials: F
authors.lastname: Theis
authors.forename: Karsten
authors.initials: K
authors.lastname: Suhre
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Ladwig
mesh_terms: D000328:Adult; D000368:Aged; D000738:Androsterone / Q000031:analogs & derivatives / Q000097:blood; D001008:Anxiety Disorders / Q000097:blood; D002110:Caffeine / Q000097:blood; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003863:Depression / Q000097:blood; D005260:Female; D006801:Humans; D007200:Indican / Q000097:blood; D007266:Inhibition, Psychological; D007737:Kynurenine / Q000097:blood; D008297:Male; D055432:Metabolomics; D008875:Middle Aged; D012307:Risk Factors; D015398:Signal Transduction / Q000502:physiology; D064415:Type D Personality; D014443:Tyrosine / Q000097:blood
chemical_list: D007737:Kynurenine; D002110:Caffeine; D014443:Tyrosine; D000738:Androsterone; D007200:Indican; C026905:androsterone sulfate