GABAA-benzodiazepine receptor availability in smokers and nonsmokers: Relationship to subsyndromal anxiety and depression

Abstract

Many smokers experience subsyndromal anxiety symptoms while smoking and during acute abstinence, which may contribute to relapse. We hypothesized that cortical gamma aminobutyric acidA-benzodiazepine receptor (GABAA-BZR) availability in smokers and nonsmokers might be related to the expression of subsyndromal anxiety, depressive, and pain symptoms. Cortical GABA A-BZRs were imaged in 15 smokers (8 men and 7 women), and 15 healthy age and sex-matched nonsmokers, and 4 abstinent tobacco smokers (3 men; 1 woman) using [123I]iomazenil and single photon emission computed tomography (SPECT). Anxiety and depressive symptoms were measured using the Spielberger's State-Trait Anxiety Index (STAI) and the Center for Epidemiology Scale for Depressive Symptoms (CES-D). The cold pressor task was administered to assess pain tolerance and sensitivity. The relationship between cortical GABA A-BZR availability, smoking status, and subsyndromal depression and anxiety symptoms, as well as pain tolerance and sensitivity, were evaluated. Surprisingly, there were no statistically significant differences in overall GABAA-BZR availability between smokers and nonsmokers or between active and abstinent smokers; however, cortical GABAA-BZR availability negatively correlated with subsyndromal state anxiety symptoms in nonsmokers but not in smokers. In nonsmokers, the correlation was seen across many brain areas with state anxiety [parietal (r = -0.47, P = 0.03), frontal (r = -0.46, P = 0.03), anterior cingulate (r = -0.47, P = 0.04), temporal (r = -0.47, P = 0.03), occipital (r = -0.43, P = 0.05) cortices, and cerebellum (r = -0.46, P = 0.04)], trait anxiety [parietal (r = -0.72, P = 0.02), frontal (r = -0.72, P = 0.02), and occipital (r = 20.65, P = 0.04) cortices] and depressive symptoms [parietal (r = 20.68; P = 0.02), frontal (r = 20.65; P = 0.03), anterior cingulate (r = -0.61; P = 0.04), and temporal (r = 20.66; P = 0.02) cortices]. The finding that a similar relationship between GABAA-BZR availability and anxiety symptoms was not observed in smokers suggests that there is a difference in GABAA-BZR function, but not number, in smokers. Thus, while subsyndromal anxiety and depressive symptoms in nonsmokers may be determined in part by GABAA-BZR availability, smoking disrupts this relationship. Aberrant regulation of GABAA-BZR function in vulnerable smokers may explain why some smokers experience subsyndromal anxiety and depression. © 2009 Wiley-Liss, Inc.