Tanabe Jody, Tregellas Jason R, Dalwani Manish, Thompson Laetitia, Owens Elizabeth, Crowley Thomas, Banich Marie
Department of Radiology, University of Denver School of Medicine, Denver, CO, USA.
Biol Psychiatry. 2009 Jan 15;65(2):160-4. doi: 10.1016/j.biopsych.2008.07.030. Epub 2008 Sep 18.
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.
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.
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.
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.
长期接触成瘾药物会导致眶额皮质（OFC）及相关边缘-前额叶通路发生细胞适应性变化，这可能是与滥用相关行为的基础。尽管存在重大负面后果，但仍倾向于做出冒险决策，这可能由物质依赖个体（SDI）的内侧OFC功能障碍介导。我们检验了以下假设：与对照受试者相比，SDI的内侧OFC灰质（GM）体积会更小。
19名SDI和20名对照受试者参与研究。SDI对两种或更多种物质成瘾，最常见的是可卡因、苯丙胺和酒精，平均戒断时间分别为4.7年、2.4年和3.2年。在3-T磁共振系统上采集高分辨率T1加权图像。使用统计参数映射（SPM）5中实现的基于体素的形态计量学（VBM）进行图像处理和分析。通过协方差分析模型测试区域GM体积的差异，对整体GM和年龄进行协变量调整。统计图谱设定为p < .05，并针对多重比较进行校正。内侧OFC GM体积与改良赌博任务中的行为表现相关。
与对照受试者相比，SDI的双侧内侧OFC中GM体积明显更小。在改良赌博任务中，内侧OFC GM与持续玩高风险牌组之间存在小但显著的相关性。
这是第一项在长期戒断后的SDI中使用VBM并进行全脑多重比较校正的研究。内侧OFC GM减少可能反映了物质依赖中病理性决策背后奖励学习回路的长期适应性变化。
