title: Insula and orbitofrontal cortical morphology in substance dependence is modulated by sex.
abstract: OBJECTIVE
  Frontolimbic circuits are involved in learning and decision-making processes thought to be affected in substance-dependent individuals. We investigated frontolimbic cortical morphometry in substance-dependent men and women and determined whether morphometric measurements correlated with decision-making performance.
  
  
  METHODS
  Twenty-eight abstinent SDI (17 men/11 women) were compared with 28 controls (13 men/15 women). Cortical thicknesses and volumes were computed by using FreeSurfer. After controlling for age and intracranial volume, group and sex effects were analyzed in 3 a priori regions of interest: the insula, orbitofrontal cortex, and anterior cingulate cortex by using analysis of covariance. A secondary whole-brain analysis was conducted to verify region-of-interest results and to explore potential differences in other brain regions.
  
  
  RESULTS
  Region-of-interest analyses revealed a main effect of group on the left insula cortex, which was thinner in SDI compared with controls (P = .02). There was a group by sex interaction on bilateral insula volume (left, P = .02; right, P = .001) and right insula cortical thickness (P = .007). Compared with same-sex controls, female SDI had smaller insulae, whereas male SDI had larger insulae. Neither ACC nor OFC significantly differed across group. Performance on a decision-making task was better in controls than SDI and correlated with OFC measurements in the controls.
  
  
  CONCLUSIONS
  SDI and controls differed in insula morphology, and those differences were modulated by sex. No group differences in OFC were observed, but OFC measurements correlated with negative-reinforcement learning in controls. These preliminary results are consistent with a hypothesis that frontolimbic pathways may be involved in behaviors related to substance dependence.
authors.affiliation: Departments of Radiology, University of Colorado School of Medicine, Denver, CO, USA.
authors.forename: J
authors.initials: J
authors.lastname: Tanabe
authors.forename: P
authors.initials: P
authors.lastname: York
authors.forename: T
authors.initials: T
authors.lastname: Krmpotich
authors.forename: D
authors.initials: D
authors.lastname: Miller
authors.forename: M
authors.initials: M
authors.lastname: Dalwani
authors.forename: J T
authors.initials: JT
authors.lastname: Sakai
authors.forename: S K
authors.initials: SK
authors.lastname: Mikulich-Gilbertson
authors.forename: L
authors.initials: L
authors.lastname: Thompson
authors.forename: E
authors.initials: E
authors.lastname: Claus
authors.forename: M
authors.initials: M
authors.lastname: Banich
authors.forename: D C
authors.initials: DC
authors.lastname: Rojas
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000473:pathology; D019969:Amphetamine-Related Disorders / Q000473:pathology; D001931:Brain Mapping / Q000379:methods; D002540:Cerebral Cortex / Q000473:pathology*; D019970:Cocaine-Related Disorders / Q000473:pathology; D005260:Female; D005625:Frontal Lobe / Q000473:pathology*; D006179:Gyrus Cinguli / Q000473:pathology; D006556:Heroin Dependence / Q000473:pathology; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008032:Limbic System / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009434:Neural Pathways; D009483:Neuropsychological Tests; D012727:Sex Characteristics; D012907:Smoking / Q000473:pathology; D019966:Substance-Related Disorders / Q000473:pathology*