长期戒断海洛因成瘾者冲动性相关脑区的结构及功能特征

冲动性是药物成瘾者的典型特征, 它既包含了抑制控制成瘾者药物使用的力量, 也包含驱动成瘾者使用药物的成分, 两者不平衡导致冲动性用药行为。海洛因成瘾者本身具有冲动性人格特质, 长时间的海洛因使用又会造成成瘾者冲动性相关的大脑结构与功能的异常。目前难以确定戒断后, 冲动性及相关的大脑结构与功能是否还呈异常状态。本研究采用基于体素的形态学分析、低频振幅、局部一致性和功能连接方法, 以35例海洛因成瘾戒断者和无任何成瘾史的健康个体26人为研究对象, 探索在长期戒断后, 海洛因成瘾者与其冲动性相关的驱动、控制系统脑网络的结构和功能情况。结果显示, 相比对照组, 戒断组灰质总体积及右内侧额上回的灰质体积显著减小, 右侧颞中回和左内侧旁扣带回的灰质体积随用药总量的增加而降低; 右侧眶部额下回与尾状核功能连接显著增强, 右侧颞中回和左侧中央前回功能连接显著降低; 右眶额中回的ReHo值、右眶额下回和左海马体的ALFF值比对照组显著更低, 而右中央后回的ReHo值显著更高。这些脑区的状况与冲动性的神经基础相吻合, 说明海洛因成瘾戒断者在戒断44个月, 奖赏、凸显、习惯性行为等网络系统仍然呈现异常状态, 且与成瘾药物使用总量有关。这些异常可能是成瘾冲动性的驱动力的神经基础, 可以作为解释成瘾者戒断后容易复吸的因素之一。

Structural and functional characteristics of impulsive-related brain regions in heroin addicts with long-term withdrawal

Impulsivity is a typical characteristic of drug addiction. In addition to the problems of inhibition and executive control, the driving force from multiple dimensions is also an important reason for impulsive drug use. The psychological drive stems from a variety of sources, including reward effect, S-R related cue response through conditioning. Low levels of inhibition are insufficient to resist the effects of the drive. This leads to an unbalanced state, which results in habitual behavior tendency. Impulsivity has both a behavioral and neural basis. Although impulsivity may be a precursor of drug use, long-term use may also damage brain structures and functions related to the inhibition of impulsive behavior. There is an open question about whether these structures and functions recover after withdrawal. In this research we used multiple imaging methods to study the extent of recovery in heroin addicts who had been abstinent for several years on average. Thirty-five abstinent heroin addicts (26 males; average period of abstinence = 43.55 months) and 26 healthy controls (26 males) were recruited using advertisements in the community. The heroin group and the healthy control group were compared on multiple measures of brain structure and function related to inhibition using the imaging methods of voxel-based morphometry (VBM), amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo). Based on the amplitude of low-frequency fluctuation (ALFF), right inferior frontal gyrus (15, 60, -6) was selected as the region of interest in which to study functional connectivity (FC). Heroin addicts showed damage in inhibition-related brain structures and functions an average of 44 months after withdrawal, and the extent of damage was correlated with lifetime dose. (1) Compared to the healthy control group, the heroin group had significantly (a) lower gray matter volume (p = 0.03) and lower whole-brain volume (p = 0.05); (b) lower gray matter in the right superior frontal gyrus (p_AlphaSim < 0.01); (c) higher regional homogeneity in right posterior central gyrus and lower regional homogeneity in right middle frontal gyrus of the orbitofrontal cortex (p_AlphaSim < 0.01); (d) lower amplitude of low-frequency fluctuation in right inferior frontal gyrus of the orbitofrontal cortex and left hippocampus (p_AlphaSim < 0.01); (e) higher functional connectivity between right inferior frontal gyrus of the orbitofrontal cortex and the right caudate, and lower functional connectivity between the right inferior frontal gyrus and right middle temporal gyrus as well left precentral gyrus (p_AlphaSim < 0.01). (2) Within the heroin group, higher lifetime dose of heroin was significantly associated with lower gray matter volume in the right middle temporal gyrus and left middle cingulate (p_AlphaSim < 0.01). The results showed that compared to healthy controls, heroin addicts had significant damage in brain structure and functions related to impulsivity even after an average period of 44 months of abstinence. In addition, the extent of damage was correlated with the lifetime dose of heroin. These results suggest that heroin addicts could continue to show impulsive behavior even after several years of abstinence, perhaps explaining the high rate of relapse in this population. Future research could test this conclusion by examining correlations between brain damage in areas related to inhibition and behavioral measures of impulsivity after a period of abstinence. The current evidence underscores the need to take impulsivity into account in relapse prevention programs for heroin addicts.