title: Medial orbitofrontal cortex gray matter is reduced in abstinent substance-dependent individuals.
abstract: BACKGROUND
  Chronic exposure to drugs of addiction induces cellular adaptations in orbitofrontal cortex (OFC) and associated limbic-prefrontal pathways that might underlie abuse-related behavior. A propensity to make risky decisions in spite of substantial negative consequences might be mediated by medial OFC dysfunction in substance-dependent individuals (SDI). We tested the hypothesis that medial OFC gray matter (GM) volume would be lower in SDI compared with control subjects.
  
  
  METHODS
  Nineteen SDI and 20 control subjects participated. The SDI were dependent on two or more substances, most often cocaine, amphetamine, and alcohol, with mean duration of abstinence 4.7, 2.4, and 3.2 years, respectively. High-resolution T1-weighted images were acquired on a 3-T magnetic resonance system. Image processing and analyses were conducted with voxel-based morphometry (VBM) implemented in Statistical Parametric Mapping (SPM) 5. Differences in regional GM volume were tested with an analysis of covariance model, co-varying for global GM and age. Statistical maps were set at p < .05, corrected for multiple comparisons. Medial OFC GM volume was correlated with behavioral performance on a modified gambling task.
  
  
  RESULTS
  There was lower GM volume specifically in bilateral medial OFC in SDI compared with control subjects. There was a small but significant correlation between medial OFC GM and persistence of playing high-risk decks on a modified gambling task.
  
  
  CONCLUSIONS
  This is the first study to use VBM with whole brain correction for multiple comparisons in SDI after prolonged abstinence. Reduced medial OFC GM might reflect long-term adaptations within the reward-learning circuit underlying pathological decision-making in substance dependence.
authors.affiliation: Department of Radiology, University of Denver School of Medicine, Denver, CO, USA. jody.tanabe@uchsc.edu
authors.forename: Jody
authors.initials: J
authors.lastname: Tanabe
authors.forename: Jason R
authors.initials: JR
authors.lastname: Tregellas
authors.forename: Manish
authors.initials: M
authors.lastname: Dalwani
authors.forename: Laetitia
authors.initials: L
authors.lastname: Thompson
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Owens
authors.forename: Thomas
authors.initials: T
authors.lastname: Crowley
authors.forename: Marie
authors.initials: M
authors.lastname: Banich
mesh_terms: D000328:Adult; D019973:Alcohol-Related Disorders / Q000473:pathology; D019969:Amphetamine-Related Disorders / Q000473:pathology; D000704:Analysis of Variance; D016022:Case-Control Studies; D019970:Cocaine-Related Disorders / Q000473:pathology; D055030:Drug Users; D005260:Female; D005625:Frontal Lobe / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000473:pathology; D009434:Neural Pathways / Q000473:pathology*; D009929:Organ Size; D012016:Reference Values; D019966:Substance-Related Disorders / Q000473:pathology*; D013695:Temperance
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