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: Jordan W Smoller, Lesley H Yamaki, Jesen A Fagerness, Joseph Biederman, Stephanie Racette, Nan M Laird, Jerome Kagan, Nancy Snidman, Stephen V Faraone, Dina Hirshfeld-Becker, Ming T Tsuang, Susan A Slaugenhaupt, Jerrold F Rosenbaum, Pamela B Sklar
• Journal: Biological psychiatry (Biol Psychiatry) Vol. 57 Issue 12 Pg. 1485-92 (Jun 15 2005) ISSN: 0006-3223 [Print] United States
• PMID: 15953484 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Corticotropin-Releasing Hormone

Topics

• Child
• Chromosome Mapping
• Corticotropin-Releasing Hormone (genetics)
• Family Health
• Female
• Follow-Up Studies
• Gene Frequency
• Genetic Predisposition to Disease
• Genotype
• Humans
• Inhibition, Psychological
• Linkage Disequilibrium
• Male
• Panic Disorder (genetics, physiopathology)
• Phenotype
• Polymorphism, Single Nucleotide
• Retrospective Studies
• Risk
• Risk Factors