Sex Differences in Gray Matter Changes and Brain-Behavior Relationships in Patients with Stimulant Dependence.

PURPOSE: 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. MATERIALS AND 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. CONCLUSION: 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.

Sex modulates approach systems and impulsivity in substance dependence.

BACKGROUND: Personality traits such as pathological engagement in approach behaviors, high levels of impulsivity and heightened negative affect are consistently observed in substance dependent individuals (SDI). The clinical course of addiction has been shown to differ between sexes. For example, women increase their rates of consumption of some drugs of abuse more quickly than men. Despite the potential influence of personality and sex on features of addiction, few studies have investigated the interaction of these factors in substance dependence. METHODS: Fifty-one SDI (26 males, 25 females) and 66 controls (41 males, 25 females) completed the Behavioral Inhibition/Behavioral Activation System (BIS/BAS) Scales, the Barratt Impulsiveness Scale, and the Positive and Negative Affect Schedule (PANAS-X). Data were analyzed with 2×2 ANCOVAs testing for main effects of group, sex and group by sex interactions, adjusting for education level. RESULTS: Significant group by sex interactions were observed for BAS scores [F(1,116)=7.03, p<.01] and Barratt Motor Impulsiveness [F(1,116)=6.11, p<.02] with female SDI showing the highest approach tendencies and impulsivity followed by male SDI, male controls, and finally female controls. SDI scored higher on negative affect [F(1,116)=25.23, p<.001] than controls. Behavioral Inhibition System scores were higher in women than men [F(1,116)=14.03, p<.001]. CONCLUSION: Higher BAS and motor impulsivity in SDI women relative to SDI men and control women suggest that personality traits that have been previously associated with drug use may be modulated by sex. These factors may contribute to differences in the disease course observed in male compared to female drug users.