Am J Psychiatry 1997; 154:1096-1100
Copyright © 1997 by American Psychiatric Association
Candidate gene study of eight GABAA receptor subunits in panic disorder
RR Crowe, Z Wang, R Noyes Jr, BE Albrecht, MG Darlison, ME Bailey, KJ Johnson and T Zoega
University of Iowa College of Medicine, Iowa City 52242-1000, USA.
OBJECTIVE: gamma-Aminobutyric acid type A (GABAA) receptor subunit genes
are candidate genes for panic disorder. Benzodiazepine agonists acting at
this receptor can suppress panic attacks, and both inverse agonists and
antagonists can precipitate them. The human GABAA receptor subtypes are
composed of various combinations of 13 subunits, each encoded by a unique
gene. The authors tested eight of these subunits in a candidate gene
linkage study of panic disorder. METHOD: In 21 U.S. and five Icelandic
multiplex pedigrees of panic disorder, 104 individuals had DSM-III-R panic
disorder (the narrowly defined affected phenotype) and 134 had either this
diagnosis or subsyndromal panic disorder characterized by panic attacks
that failed to meet either the criterion of attack frequency or the number
of criterion symptoms necessary for a definite diagnosis (the broadly
defined affected phenotype). The authors conducted lod score linkage
analyses with both phenotypes using both a dominant and a recessive model
of inheritance for the following loci: GABRA1-GABRA5 (alpha 1-alpha 5),
GABRB1 (beta 1), GABRB3 (beta 3), and GABRG2 (gamma 2). RESULTS: The
results failed to support the hypothesis that any of these genes cause
panic disorder in a majority of the pedigrees. CONCLUSIONS: Within the
limitations of the candidate gene linkage method, panic disorder does not
appear to be caused by mutation in any of the eight GABAA receptor genes
tested.
