title: 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 acid(A)-benzodiazepine receptor (GABA(A)-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 [(123)I]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 GABA(A)-BZR availability between smokers and nonsmokers or between active and abstinent smokers; however, cortical GABA(A)-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 = -0.65, P = 0.04) cortices] and depressive symptoms [parietal (r = -0.68; P = 0.02), frontal (r = -0.65; P = 0.03), anterior cingulate (r = -0.61; P = 0.04), and temporal (r = -0.66; P = 0.02) cortices]. The finding that a similar relationship between GABA(A)-BZR availability and anxiety symptoms was not observed in smokers suggests that there is a difference in GABA(A)-BZR function, but not number, in smokers. Thus, while subsyndromal anxiety and depressive symptoms in nonsmokers may be determined in part by GABA(A)-BZR availability, smoking disrupts this relationship. Aberrant regulation of GABA(A)-BZR function in vulnerable smokers may explain why some smokers experience subsyndromal anxiety and depression.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, Veteran's Affairs Connecticut Healthcare System (VACHS), 116A6 West Haven, Connecticut 06516, USA. irina.esterlis@yale.edu
authors.forename: Irina
authors.initials: I
authors.lastname: Esterlis
authors.forename: Kelly P
authors.initials: KP
authors.lastname: Cosgrove
authors.forename: Jeffery C
authors.initials: JC
authors.lastname: Batis
authors.forename: Frederic
authors.initials: F
authors.lastname: Bois
authors.forename: Tracy A
authors.initials: TA
authors.lastname: Kloczynski
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Stiklus
authors.forename: Edward
authors.initials: E
authors.lastname: Perry
authors.forename: Gilles D
authors.initials: GD
authors.lastname: Tamagnan
authors.forename: John P
authors.initials: JP
authors.lastname: Seibyl
authors.forename: Robert
authors.initials: R
authors.lastname: Makuch
authors.forename: Suchitra
authors.initials: S
authors.lastname: Krishnan-Sarin
authors.forename: Stephanie
authors.initials: S
authors.lastname: O'Malley
authors.forename: Julie K
authors.initials: JK
authors.lastname: Staley
mesh_terms: D000328:Adult; D001007:Anxiety / Q000000981:diagnostic imaging / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D001931:Brain Mapping; D003863:Depression / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D005442:Flumazenil / Q000031:analogs & derivatives; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010146:Pain / Q000000981:diagnostic imaging / Q000378:metabolism; D010147:Pain Measurement; D011569:Psychiatric Status Rating Scales; D011963:Receptors, GABA-A / Q000378:metabolism*; D012907:Smoking / Q000378:metabolism*; D011795:Surveys and Questionnaires; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D011963:Receptors, GABA-A; D005442:Flumazenil; C063038:iomazenil