title: Sex, GABA, and nicotine: the impact of smoking on cortical GABA levels across the menstrual cycle as measured with proton magnetic resonance spectroscopy.
abstract: BACKGROUND
  Given that nicotine modulates amino acid neurotransmission, we sought to examine the impact of nicotine on cortical gamma-aminobutyric acid (GABA) levels in male and female smokers.
  
  
  METHODS
  Healthy nicotine-dependent men (n = 10) and women (n = 6) underwent proton magnetic resonance spectroscopy (1H-MRS) to measure occipital cortex GABA concentrations. A subset of the smoking men (n = 5) underwent 1H-MRS scans before and after 48 hours of smoking abstinence, whereas each of the women were scheduled to undergo pre- and postabstinence scans during the follicular and luteal phases of one menstrual cycle. Healthy nonsmoking men (n = 7) and women (n = 13) underwent 1H-MRS for comparison.
  
  
  RESULTS
  Short-term abstinence had no significant effect on cortical GABA concentrations in either men or women. There was, however, a significant effect of sex, diagnosis (smoker/nonsmoker), and menstrual cycle phase on cortical GABA levels, such that female smokers experienced a significant reduction in cortical GABA levels during the follicular phase and no cyclicity in GABA levels across the menstrual cycle, whereas cortical GABA levels were similar in smoking and nonsmoking men.
  
  
  CONCLUSIONS
  Taken together with previous 1H-MRS data showing abnormalities in occipital cortex GABA concentrations in several affective disorders, our preliminary finding that nicotine modulation of GABA levels varies by sex provides a further rationale for investigating the impact of nicotine on central GABAergic function as a potential risk factor for women to experience depressive symptoms during smoking cessation.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, University Towers Suite 2H, 100 York Street, New Haven, CT 06511, USA. neill.epperson@yale.edu
authors.forename: C Neill
authors.initials: CN
authors.lastname: Epperson
authors.forename: Stephanie
authors.initials: S
authors.lastname: O'Malley
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Czarkowski
authors.forename: Ralitza
authors.initials: R
authors.lastname: Gueorguieva
authors.forename: Peter
authors.initials: P
authors.lastname: Jatlow
authors.forename: Gerard
authors.initials: G
authors.lastname: Sanacora
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Rothman
authors.forename: John H
authors.initials: JH
authors.lastname: Krystal
authors.forename: Graeme F
authors.initials: GF
authors.lastname: Mason
mesh_terms: D000328:Adult; D003367:Cotinine / Q000378:metabolism; D004958:Estradiol / Q000097:blood; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008597:Menstrual Cycle / Q000378:metabolism*; D008875:Middle Aged; D009778:Occipital Lobe / Q000378:metabolism; D011374:Progesterone / Q000097:blood; D011522:Protons; D012727:Sex Characteristics; D012907:Smoking / Q000378:metabolism*; D016540:Smoking Cessation / Q000379:methods; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D011522:Protons; D011374:Progesterone; D004958:Estradiol; D005680:gamma-Aminobutyric Acid; D003367:Cotinine