title: Evaluation of gender difference in regional brain metabolic responses to lorazepam.
abstract: Women are prescribed benzodiazepines twice as frequently as men and there is evidence of differences in therapeutic responsiveness to benzodiazepines between genders. In this study we compared the regional brain metabolic response to benzodiazepines between male and female subjects. Sixteen healthy men and 12 healthy women were scanned with positron emission tomography (PET) and [F-18] fluorodeoxyglucose (FDG) twice: prior to placebo and prior to lorazepam (30 microg/kg) on separate days. Lorazepam significantly and consistently decreased whole brain metabolism and the magnitude as well as the regional pattern of the changes was comparable for both genders (M = -4.7+/- 3 and F = -3.9 +/- 3.8 micromol/100 g/min). Lorazepam effects were largest in thalamus (- 12.5 +/- 6.2 and -8.6 +/- 7.1 micromol/100 g/min) and occipital cortex (-10.5 +/- 5.5 and -10.1 +/- 6.6 micromol/100 g/min). Lorazepam-induced changes in 'relative' metabolism were also similar for both genders except for trend differences (0.01 < P < 0.05) in rectal gyrus, where lorazepam increased relative metabolism in women (+4.4 +/- 9.9%) whereas it decreased in men (-3.2 +/- 8.8%, P < 0.04) and in cerebellum, where lorazepam-induced decrements were larger in women (-5.9 +/- 6%) than in men (-1.1% +/- 6.6%, P < 0.05). There were no differences between genders for any of the behavioral effects of lorazepam. In summary, this study does not show differences in the response to lorazepam between the genders as assessed by its behavioral effects and the changes in absolute metabolism; the trend toward a difference in the relative changes in rectal gyrus and cerebellum merits further investigation.
authors.affiliation: Medical Department, Brookhaven National Laboratory, Upton, NY 11973, USA. gjwang@bnl.gov
authors.forename: G J
authors.initials: GJ
authors.lastname: Wang
authors.forename: N D
authors.initials: ND
authors.lastname: Volkow
authors.forename: J S
authors.initials: JS
authors.lastname: Fowler
authors.forename: R J
authors.initials: RJ
authors.lastname: Hitzemann
authors.forename: N R
authors.initials: NR
authors.lastname: Pappas
authors.forename: N
authors.initials: N
authors.lastname: Netusil
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D003071:Cognition / Q000187:drug effects; D005260:Female; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism; D006179:Gyrus Cinguli / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008140:Lorazepam / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011597:Psychomotor Performance / Q000187:drug effects; D012737:Sex Factors; D016037:Single-Blind Method; D014055:Tomography, Emission-Computed
chemical_list: D014151:Anti-Anxiety Agents; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D005947:Glucose; D008140:Lorazepam