GABA(A) receptor beta 3 subunit gene and psychiatric morbidity in a post-traumatic stress disorder population

GABAergic systems have been implicated in the pathogenesis of anxiety, depr ession and insomnia. These symptoms are part of the core and comorbid psych iatric disturbances in post-traumatic stress disorder (PTSD) In a sample of Caucasian male PTSD patients, dinucleotide repeat polymorphisms of the GAB AA receptor beta3 subunit gene were compared to scores on the General Healt h Questionnaire-28 (GHQ). As the major allele at this gene locus (GABRB3) w as GI, the alleles were divided into GI and non-GI groups. On the total sco re of the GHQ, which comprises the somatic symptoms, anxiety/insomnia, soci al dysfunction and depression subscales, patients with the GI non-GI genoty pe had a significantly higher score when compared to either the G1G1 genoty pe (alpha = 0.01) or the non-GI non-GI genotype (alpha = 0.05). No signific ant difference was found between the G1G1 and non-Gl non-G1 genotypes. When the GI non-G1 heterozygotes were compared to the combined G1G1 and non-GI non-GI homozygotes, a significantly higher total GHQ score was found in the heterozygotes (P = 0.002). These observations suggest a heterosis effect. Further analysis of GHQ subscale scores showed that heterozygotes compared to the combined homozygotes had higher scores on the somatic symptoms (P = 0.006), anxiety/insomnia (P = 0.003), social dysfunction (P = 0.054) and de pression (P = 0.004) subscales. In conclusion, the present study indicates that in a population of PTSD patients, heterozygosity of the GABRB3 major ( GI) allele confers higher levels of somatic symptoms, anxiety/insomnia, soc ial dysfunction and depression than found in homozygosity. (C) 2001 Elsevie r Science Ireland Ltd. All rights reserved.