Elsevier

Biological Psychiatry

Volume 65, Issue 2, 15 January 2009, Pages 160-164
Biological Psychiatry

Research Report
Medial Orbitofrontal Cortex Gray Matter Is Reduced in Abstinent Substance-Dependent Individuals

https://doi.org/10.1016/j.biopsych.2008.07.030Get rights and content

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.

Section snippets

Subjects

Thirty-nine subjects, including 20 control subjects (14 women/6 men, 33 years old, SD 11 years) and 19 SDI (9 women/10 men, 35 years old, SD 7 years) participated in this study. The SDI were recruited from the University of Colorado School of Medicine Addiction Research and Treatment Service (ARTS), a long-term residential treatment service. Inclusion criteria included dependence on one or more illicit substances, with DSM-IV criteria. Inclusion criteria for the control subjects were no

Results

There was no difference in age or gender between the groups. There were differences in education and IQ between the groups. IQ and education were correlated (p = .03). Table 1 shows the number of SDI meeting criteria for dependence or abuse. There was considerable variation in duration of abstinence across and within different drugs. Average abstinence from cocaine, alcohol, and amphetamine was 4.7, 3.2, and 2.4 years, respectively.

Discussion

The finding of reduced medial OFC GM in SDI compared with control subjects is consistent with previous studies. Franklin et al. (10) were the first to report lower GM in cocaine-dependent subjects compared with control subjects with VBM methods. They observed lower GM density in ventral medial OFC, anterior cingulate, and anterior insula. Lyoo et al. (11) found lower GM in bilateral medial OFC in opiate-dependent subjects compared with control subjects. Less GM was also found in superior and

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