title: Catechol-O-methyltransferase modulation of cortisol secretion in psychiatrically at-risk and healthy adolescents.
abstract: OBJECTIVE
  Recent research implicates the catechol-O-methyltransferase (COMT) ValMet polymorphism in stress sensitivity, through modulation of hypothalamic-pituitary-adrenal (HPA) function. In healthy samples, Met homozygosity has been associated with greater HPA activity (i.e., cortisol) and stress sensitivity, though findings are mixed among clinical samples. To date, there are no reports examining baseline or longitudinal changes in HPA activity as a function of COMT genotype in youth. This study tested the hypothesis that COMT genotype would be associated with cortisol secretion in normal and at-risk adolescents; specifically, that COMT genotype would be linked in a dose-response manner such that Met homozygotes would have the highest salivary cortisol levels, followed by heterozygotes, then Val homozygotes. In addition, this study examined the relation of COMT genotype with longitudinal changes in cortisol.
  
  
  METHODS
  This study examined the association of COMT with salivary cortisol across a 1-year period in healthy and at-risk adolescents with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision Axis II diagnoses.
  
  
  RESULTS
  Results indicated higher cortisol levels for Met homozygotes (compared with heterozygotes and Val homozygotes) at the 1-year follow-up, and increased mean cortisol levels across a 1-year period among Met carriers, suggesting that COMT associates with differences in cortisol secretion during adolescence.
  
  
  CONCLUSIONS
  Findings are discussed with respect to COMT genotype as a potential genetic indicator of psychiatric risk that modulates developmental changes in HPA activity.
authors.affiliation: Department of Psychology, Brooklyn College and The Graduate Center of The City University of New York, New York 11210, USA. dwalder@brooklyn.cuny.edu
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Walder
authors.forename: Hanan D
authors.initials: HD
authors.lastname: Trotman
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Cubells
authors.forename: Joy
authors.initials: J
authors.lastname: Brasfield
authors.forename: Yi-Lang
authors.initials: YL
authors.lastname: Tang
authors.forename: Elaine F
authors.initials: EF
authors.lastname: Walker
mesh_terms: D000293:Adolescent; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002648:Child; D020022:Genetic Predisposition to Disease; D006262:Health; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D001523:Mental Disorders / Q000201:enzymology* / Q000235:genetics*; D012307:Risk Factors; D012463:Saliva / Q000378:metabolism
chemical_list: D002394:Catechol O-Methyltransferase; D006854:Hydrocortisone