title: The corticotropin-releasing hormone gene and behavioral inhibition in children at risk for panic disorder.
abstract: BACKGROUND
  Behavioral inhibition to the unfamiliar (BI) is a heritable temperamental phenotype involving the tendency to display fearful, avoidant, or shy behavior in novel situations. BI is a familial and developmental risk factor for panic and phobic anxiety disorders. We previously observed an association between BI and a microsatellite marker linked to the corticotropin releasing hormone (CRH) gene in children at risk for panic disorder. To evaluate this further, we genotyped additional families for this marker and a panel of markers encompassing the CRH locus.
  
  
  METHODS
  Sixty-two families that included parents with panic disorder and children who underwent laboratory-based behavioral observations were studied. Family-based association tests and haplotype analysis were used to evaluate the association between BI and polymorphisms spanning the CRH locus.
  
  
  RESULTS
  We examined a set of markers which we found to reside in a block of strong linkage disequilibrium encompassing the CRH locus. The BI phenotype was associated with the microsatellite marker (p=.0016) and three single nucleotide polymorphisms (SNPs), including a SNP in the coding sequence of the gene (p=.023). Haplotype-specific tests revealed association with a haplotype comprising all of the markers (p=.015).
  
  
  CONCLUSIONS
  These results suggest that the CRH gene influences inhibited temperament, a risk factor for panic and phobic anxiety disorders. Genetic studies of anxiety-related temperament represent an important strategy for identifying the genetic basis of anxiety disorders.
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, Boston 02114, USA. jsmoller@hms.harvard.edu
authors.forename: Jordan W
authors.initials: JW
authors.lastname: Smoller
authors.forename: Lesley H
authors.initials: LH
authors.lastname: Yamaki
authors.forename: Jesen A
authors.initials: JA
authors.lastname: Fagerness
authors.forename: Joseph
authors.initials: J
authors.lastname: Biederman
authors.forename: Stephanie
authors.initials: S
authors.lastname: Racette
authors.forename: Nan M
authors.initials: NM
authors.lastname: Laird
authors.forename: Jerome
authors.initials: J
authors.lastname: Kagan
authors.forename: Nancy
authors.initials: N
authors.lastname: Snidman
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Faraone
authors.forename: Dina
authors.initials: D
authors.lastname: Hirshfeld-Becker
authors.forename: Ming T
authors.initials: MT
authors.lastname: Tsuang
authors.forename: Susan A
authors.initials: SA
authors.lastname: Slaugenhaupt
authors.forename: Jerrold F
authors.initials: JF
authors.lastname: Rosenbaum
authors.forename: Pamela B
authors.initials: PB
authors.lastname: Sklar
mesh_terms: D002648:Child; D002874:Chromosome Mapping; D003346:Corticotropin-Releasing Hormone / Q000235:genetics*; D005192:Family Health; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007266:Inhibition, Psychological; D015810:Linkage Disequilibrium; D008297:Male; D016584:Panic Disorder / Q000235:genetics* / Q000503:physiopathology*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D012306:Risk; D012307:Risk Factors
chemical_list: D003346:Corticotropin-Releasing Hormone