title: Sex Differences in Gray Matter Changes and Brain-Behavior Relationships in Patients with Stimulant Dependence.
abstract: OBJECTIVE
  To investigate whether sex modulates the effects of stimulant dependence on gray matter volume (GMV) in patients who have achieved long-term abstinence and to characterize how sex modulates GMV according to specific behavioral measures, such as dependence symptom count, behavioral approach, and impulsivity.
  
  
  METHODS
  Colorado Multiple Institutional Review Board approval and informed consent were obtained. In this prospective parallel group study, 127 age- and sex-matched participants (68 control subjects [28 women, 40 men] and 59 patients with stimulant dependence [28 women, 31 men]) underwent T1-weighted spoiled gradient-echo inversion recovery magnetic resonance imaging of the brain at 3 T. Images were segmented by using voxel-based morphometric software. After adjustment for age, education, and head size, the effects of group according to sex on GMV and main effects were analyzed throughout the whole brain by using an analysis of covariance family-wise cluster corrected for multiple comparisons, with a threshold P value of less than .05. Dependence symptom count and behavioral measurements were correlated with GMV in the whole brain and in five a priori regions of interest.
  
  
  RESULTS
  The effects of group according to sex on GMV were significant in numerous regions (P < .001). Compared with female control subjects, women with stimulant dependence had significantly lower GMV in widespread brain regions (P < .001). There were no significant differences in GMV between male control subjects and men with stimulant dependence (P = .625). Dependence symptom count negatively correlated with GMV in the nucleus accumbens in women (left: r = -0.364, P = .047; right: r = -0.407, P = .031) but not in men (left: r = -0.063, P = .737; right: r = -0.174, P = .349). Behavioral approach (P = .002) and impulsivity (P = .013) correlated negatively with frontal and temporal GMV changes in women with stimulant dependence but not in the other groups.
  
  
  CONCLUSIONS
  Vast changes in GMV were observed in women with stimulant dependence after prolonged abstinence, but were not observed in men. Sexual dimorphism in drug-related neuroanatomic changes and brain-behavior relationships may be mechanisms underlying the difference in clinical profiles of addiction between women and men.
authors.affiliation: From the Departments of Bioengineering (M.F.R.), Radiology (D.Y., R.I.P., J.M.H., J.T.), and Psychiatry (M.D., J.T.S.), University of Colorado School of Medicine, 12700 E 19th Ave, C278, Aurora, CO 80045.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Regner
authors.affiliation: From the Departments of Bioengineering (M.F.R.), Radiology (D.Y., R.I.P., J.M.H., J.T.), and Psychiatry (M.D., J.T.S.), University of Colorado School of Medicine, 12700 E 19th Ave, C278, Aurora, CO 80045.
authors.forename: Manish
authors.initials: M
authors.lastname: Dalwani
authors.affiliation: From the Departments of Bioengineering (M.F.R.), Radiology (D.Y., R.I.P., J.M.H., J.T.), and Psychiatry (M.D., J.T.S.), University of Colorado School of Medicine, 12700 E 19th Ave, C278, Aurora, CO 80045.
authors.forename: Dorothy
authors.initials: D
authors.lastname: Yamamoto
authors.affiliation: From the Departments of Bioengineering (M.F.R.), Radiology (D.Y., R.I.P., J.M.H., J.T.), and Psychiatry (M.D., J.T.S.), University of Colorado School of Medicine, 12700 E 19th Ave, C278, Aurora, CO 80045.
authors.forename: Robert I
authors.initials: RI
authors.lastname: Perry
authors.affiliation: From the Departments of Bioengineering (M.F.R.), Radiology (D.Y., R.I.P., J.M.H., J.T.), and Psychiatry (M.D., J.T.S.), University of Colorado School of Medicine, 12700 E 19th Ave, C278, Aurora, CO 80045.
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Sakai
authors.affiliation: From the Departments of Bioengineering (M.F.R.), Radiology (D.Y., R.I.P., J.M.H., J.T.), and Psychiatry (M.D., J.T.S.), University of Colorado School of Medicine, 12700 E 19th Ave, C278, Aurora, CO 80045.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Honce
authors.affiliation: From the Departments of Bioengineering (M.F.R.), Radiology (D.Y., R.I.P., J.M.H., J.T.), and Psychiatry (M.D., J.T.S.), University of Colorado School of Medicine, 12700 E 19th Ave, C278, Aurora, CO 80045.
authors.forename: Jody
authors.initials: J
authors.lastname: Tanabe
mesh_terms: D000328:Adult; D001921:Brain / Q000503:physiopathology*; D005260:Female; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D012737:Sex Factors; D019966:Substance-Related Disorders / Q000473:pathology* / Q000503:physiopathology*