TDT analysis of glutamate decarboxylase (65-KDA ISOform) in behavioral inhibition

Behavioral inhibition (BI), a heritable temperamental predisposition, appears to be a risk factor for the development of panic and phobic anxiety disorders. The glutamic acid decarboxylase 65kDa isoform (GAD65) regulates GABA synthesis in response to environmental stress. A mouse knockout of GAD65 exhibits increased anxiety and behavioral inhibition as well as diminished response to benzodiazepines, making it an intriguing candidate gene for human BI and anxiety disorders. We tested for association between the GAD65 gene and BI using a dinucleotide repeat polymorphism tightly linked to GAD65. Subjects comprised families participating in a study of children at risk for anxiety disorders. Children aged 21 months, 4 years or 6 years underwent behavioral assessments for BI. Genotypes are available for 62 families (107 informative transmissions). A multiallelic TDT analysis revealed no evidence of association between GAD and BI in this sample (p = 0.40). Nevertheless, this study illustrates an approach to the genetic dissection of panic and phobic anxiety disorders based on candidate genes derived from mouse models of behavioral inhibition.