GABA_A‐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 aminobutiric acid A – benzodiazepine receptor (GABAA-BZR) availability in smokers and nonsmokers might be related to the expression of subsyndromal anxiety, depressive, and pain symptoms. Cortical GABAA-BZRs were imaged in 15 smokers (8 men; 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 GABAA-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 state anxiety brain areas [parietal (r=−.47, p=.03), frontal (r=−.46, p=.03), anterior cingulate (r=−.47, p=.04), temporal (r=−.47, p=.03), occipital (r=−.43, p=.05) cortices, and cerebellum (r=−.46, p=.04)], trait anxiety [parietal (r=−.72, p=.02), frontal (r=−.72, p=.02), and occipital (r=−.65, p=.04) cortices] and depressive symptoms [parietal (r=− .68; p=.02), frontal (r=−.65; p=.03), anterior cingulate (r=−.61; p=.04), and temporal (r=−.66; p=.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.

Sex‐specific differences in GABAA‐benzodiazepine receptor availability: relationship with sensitivity to pain and tobacco smoking craving

“…However, a preliminary study conducted in our laboratory did not reveal a significant effect of tobacco smoking on the GABA A -BZR availability. Specifically, we did not detect significant differences in GABA A -BZR availability in living human tobacco smokers compared to nonsmokers, nor did we observe a difference in GABA A -BZR availability from baseline to abstinence in a small subset of smokers who agreed to abstain from smoking for 5 weeks and repeated the scanning protocol (Esterlis et al, 2009). The difference observed between the above mentioned rodent study and our human study may be due to a sex-specific regulation of GABA levels by sex-steroid hormones, which in nonsmoking women are highest during the follicular phase and lowest in the luteal phase (Epperson et al, 2002).…”

Evidence for GABA‐A receptor dysregulation in gambling disorder: correlation with impulsivity

“…However, evidence from neuroimaging studies using non‐specific benzodiazepine radiotracers [ 11 C]flumazenil PET or [ 123 I]iomazenil SPET about GABA A receptor availability within the amygdala in relation to these processes is limited and inconsistent. The most evidence relates to anxiety where no relationship or negative correlations have been reported in HV and both positive and negative correlations in patients with anxiety disorders (Abadie et al 1999; Esterlis et al 2009; Hasler et al 2008; Lingford‐Hughes et al 1998). …”

Neuroimaging insights into the role of cortical GABA systems and the influence of nicotine on the recovery from alcohol dependence

“…The effects of chronic nicotine administration on GABA activity are less clear. While a preclinical study indicated chronic nicotine treatment increased the density of BZ receptors in the cerebral cortex (Magata et al, 2000), a recent neuroimaging study in our laboratory demonstrated no difference in GABA A -BZR availability between current healthy smokers and nonsmokers (Esterlis et al, 2009). An important caveat to this study is that smokers were imaged at 7 hours of smoking abstinence.…”