【作者】 廖艳辉；

【导师】 郝伟；

【作者基本信息】 中南大学 ， 精神病与精神卫生学， 2010， 博士

【摘要】 目的：了解氯胺酮依赖者、吸烟者和正常对照者的认知功能差异。方法：采用认知功能测试量表(包括：数字符号测验、连线测试A和stroop色词测验)对三组人群进行认知功能测试。结果：氯胺酮依赖者在数字符号测验和stroop色词测验方面得分都明显较吸烟者及正常对照者低,而吸烟者与正常对照没有明显的差异。结论：本测试结果显示氯胺酮依赖者可能存在认知功能损害,进一步支持本研究的神经影像学研究结果,而吸烟者可能没有明显的认知功能损害。目的：采用磁共振弥散张量成像技术,探讨氯胺酮依赖者的脑白质改变情况。方法：使用弥散张量成像的方法比较了41例氯胺酮依赖者和44例与之相匹配的无任何物质依赖史的健康志愿者的脑白质的完整性。结果：氯胺酮依赖者双侧额叶区和左侧颞-顶叶区的白质FA值低于正常对照(P<0.05,纠正后,cluster水平),同时还发现氯胺酮成瘾者的FA值与估计的氯胺酮使用总量呈负相关,即氯胺酮依赖者使用氯胺酮越多、脑白质损害越严重。结论：首次发现氯胺酮依赖者存在双侧额叶区和左侧颞-顶叶区脑白质完整性的损害；而且,双侧额叶区的脑白质的损害程度与使用氯胺酮的总量相关,说明使用氯胺酮越频繁、量越大,对脑白质的损害也越大。此外,氯胺酮依赖者的白质损害相似于精神分裂症者的白质损害,进一步支持氯胺酮作为精神分裂症研究模型的观点。目的：采用磁共振三维成像技术,研究氯胺酮依赖者脑灰质改变情况。方法：我们采用基本体素的形态学分析方法对41名氯胺酮依赖者和44名未使用任何成瘾物质的健康志愿者进行两组之间的脑灰质体积比较。结果：结果表明,与对照组相比,氯胺酮依赖组的双侧额叶区(左额上回和右额中回)灰质体积下降(p<0.05,纠正后,cluster水平)。此外,我们发现氯胺酮使用的时间(月)与双侧额叶灰质体积呈负相关(使用时间越长,灰质体积越少),而估计的氯胺酮使用总量只和左额上回的灰质体积呈负相关。结论：本研究首次报道了氯胺酮依赖者的双侧额叶灰质体积下降,首次分析了氯胺酮依赖者使用氯胺酮的相关因素与脑灰质体积的关系。氯胺酮依赖者的脑结构损害的研究,为将来氯胺酮成瘾和其他物质成瘾的治疗提供研究方向,也支持了氯胺酮作为模拟精神分裂症模型的研究的可行性和精神分裂症的谷氨酸假设。目的：采用功能磁共振(fMRI)磁共振技术,探讨静息状态下氯胺酮依赖者的脑功能活动改变情况。方法：本研究采用局部一致性(ReHo)方法,对41例氯胺酮依赖者和44例与之相匹配的无任何物质依赖的健康志愿者在静息状态下脑功能活动情况进行比较分析。结果：与正常人相比,氯胺酮依赖者静息状态下前扣带回的BOLD信号ReHo降低(P<0.05,纠正后,cluster水平),同时还发现氯胺酮成瘾者静息状态下额叶中央前回的BOLD信号ReHo增强(P<0.05,纠正后)。额叶中央前回的ReHo值增加与总的氯胺酮使用量和对氯胺酮的渴求呈负相关。结论：首次采用ReHo方法分析氯胺酮依赖者静息状态下脑的BOLD信号变化的脑区。此研究提示氯胺酮依赖者额叶区功能活动也存在异常。目的：采用磁共振弥散张量成像技术,探讨慢性吸烟者的脑白质损害情况。方法：使用弥散张量成像(DTI)的方法对44名慢性吸烟者和44名与之相匹配的非吸烟者的脑白质的完整性进行比较。结果：慢性吸烟组的双侧顶额叶区白质FA值高于非吸烟组(P<0.05,纠正后,cluster水平)。两侧的差异区非常的对称,除此之外没有发现两组白质有差异的脑区。此外,我们发现慢性吸烟者的FA值增高与首次吸烟的年龄相关,即首次吸烟的年龄越小,FA值增高越明显。结论：本研究显示慢性吸烟导致双侧顶额叶区白质对称性的改变,研究结果支持了慢性吸烟引起双侧顶-额区连接改变的假设,说明青少年吸烟可能对以后脑白质发育有影响。目的：采用磁共振三维成像技术,研究慢性吸烟者的脑灰质改变情况。方法：我们采用基于体素的形态学分析方法对44名吸烟者和44名相匹配的不吸烟者进行两组之间的脑灰质体积比较。结果：本研究发现,与不吸烟者组相比,吸烟者组的左侧丘脑、额中回区和扣带回灰质体积下降(p<0.001,未纠正)。结论：本研究发现了慢性吸烟者丘脑、额中回区和扣带回灰质体积下降。本研究结果将有助于进一步研究慢性吸烟的大脑作用机制。目的：采用功能磁共振(fMRI)磁共振技术,探讨慢性吸烟者静息状态下的脑功能活动情况。方法：本研究采用局部一致性(ReHo)方法,对44名吸烟者和44名与之相匹配的不吸烟的健康志愿者在静息状态下脑功能活动情况进行比较分析。结果：与不吸烟者相比,吸烟者静息状态右侧额下回BOLD信号ReHo降低,左侧顶上回BOLD信号ReHo增强(P<0.05,纠正后,cluster水平)。结论：首次采用ReHo方法分析吸烟者静息状态下脑的BOLD信号变化的脑区。此研究提示慢性吸烟会导致脑功能活动的改变。目的：探讨氯胺酮依赖者、吸烟者对不同成瘾物质(氯胺酮使用、吸烟)诱导的脑功能活动的异同之处。方法：采用氯胺酮使用、吸烟相关、性相关的短片录像对41名氯胺酮依赖(合并吸烟)者、45名吸烟者和44名无任何成瘾物质依赖者进行进行功能磁共振,观察脑功能活动变化。结果：对氯胺酮相关刺激,吸烟者组与对照组之间没有差异,而氯胺酮依赖者有不同部位脑区功能活动降改变；对吸烟相关刺激,无论与不吸烟者还是氯胺酮依赖者相比,吸烟者的脑功能增强；对性行为相关刺激,氯胺酮依赖者组的脑功能活动降低,而吸烟者组和不吸烟者组之间没有差异。结论：本测试结果显示氯胺酮使用和吸烟诱导的脑功能反应区涉及到多个脑区活动改变,与成瘾的神经病理学机制相关。更多还原

【Abstract】 Objective:To explore the differences of cognitive function between ketamine users, smokers and healthy controls. Methods:Digit Symbol Test, Trail Making Test and The Stroop Color-Word Test were used to measure the differences of cognitive function in ketamine dependent subjects, smokers and drug free healthy volunteers. Results:compared with smokers and healthy controls, ketamine abuser had significant lower scores in Digit Symbol Test and the Stroop Color-Word Test, but no difference in Trail Making Test. Conclusions:The findings suggest that ketamine abusers have cognitive deficits which supported our finding in neuroimaging studies. However, this test did not show cognitive impairment in chronic cigarette smokers.Objective:To assess the brain white matter integrity in patients with ketamine dependence. Methods:White matter volumes were measured by using in vivo diffusion tensor magnetic resonance imaging (DTI) data in 41ketamine dependent subjects and 44 drug free healthy volunteers. Results: White matter changes associated with chronic ketamine use were found in bilateral frontal and left temporo-parietal cortices. Further, frontal white matter fractional anisotropy (FA) correlated with the severity of drug use (as measured by estimated total ketamine consumption). Conclusions:We provide direct evidence for dose-dependent abnormalities of white matter in bilateral frontal region and left temporo-parietal following chronic ketamine. The findings suggest a microstructural basis for the cognitive changes observed with prolonged ketamine use. Moreover, their similarity to white matter changes observed in chronic schizophrenia have implications for the glutamate model of this illness.Objective:To assess volumetric abnormalities of grey matter in ketamine dependent subjects. Methods:We used voxel based morphometry in conjunction with statistical parametric mapping on the structural magnetic resonance images of ketamine-dependent (n= 41) and drug-naive control individuals (n= 44) to assess differences between the two groups in gray matter volume. Results:We found a decrease in gray matter volume in bilateral frontal (left superior frontal and right middle frontal) cortex of ketamine patients in comparison to controls (p<0.05 corrected for multiple comparisons at cluster-level). Also, we found that the duration (months) of ketamine use was negatively correlated with gray matter volume in bilateral frontal cortex while the estimated total lifetime ketamine consumption was only negatively correlated with gray matter volume in left superior frontal cortex. Conclusions:This is the first voxel-based morphometry study showing reduction of frontal gray matter volume in patients with ketamine dependence and showing the correlation of duration of ketamine use and cumulative doses of ketamine with decrease of frontal gray matter volume. Brian structural study of the affected areas in patients with ketamine dependence might better guide future research into the poorly understood condition of ketamine addiction and its correlates of schizophrenia.Objective:To assess the alterations in regional homogeneity of resting-state brain activity in ketamine dependence. Methods:In this study, 41 patients with ketamine dependence and 44 healthy control subjects being imaged with BOLD fMRI and analyzed with the ReHo method. Results: Compared with healthy controls, decreased ReHo was found in ketamine users in the right Anterior Cingulate and increased ReHo was found in left Frontal Lobe (Precentral Gyrus) (p<0.05, cluster-level corrected). We also observed negative correlations between increased ReHo in precentral frontal gyrus and estimated total lifetime ketamine consumption, ketamine craving. Conclusions:To our knowledge, this is the first time to find the changes of the resting-state of brain activity in patients with ketamine dependence. Our findings indicated abnormal brain activity was distributed frontal cortex in patients with ketamine dependence during resting state.Objective:To assess the Brain white matter integrity in chronic cigarette smokers using diffusion tensor imaging (DTI). Methods:Brain magnetic resonance imaging (MRI) was performed for 44 smokers and 44 healthy age-and sex-matched comparison non-smoking subjects to compare the alteration of white matter integrity as measured by the fractional anisotropy (FA) on diffusion tensor imaging (DTI). Results:DTI data revealed that smokers had higher fractional anisotropy than healthy non-smokers in almost symmetrically bilateral fronto-parietal region white matter. FA differences were not seen in other areas. Positive association between the first start smoking age and increased fractional anisotropy was found in chronic smokers. Conclusions:The data suggest that smokers and non-smokers differed in bilateral fronto-parietal region white matter. These findings support the hypothesis that chronic cigarette smoking involves alterations of bilateral fronto-parietal connectivity and suggest that adolescent cigarette exposure modulates the development of white matter in brain. Objective:To assess volumetric abnormalities of grey matter in chronic cigarette smokers. Methods:We used voxel based morphometry in conjunction with statistical parametric mapping on the structural magnetic resonance images of 44 smokers and 44 non-smoking control individuals to assess gray matter volume differences between the two groups. Results:We found a decrease in gray matter volume in left thalamus, medial frontal cortex and anterior cingulate of smokers in comparison to controls (p<0.001 uncorrected for multiple comparisons at voxel-level). Conclusions:This voxel-based morphometry study showing reduction of regional gray matter volume in smokers. Brian structural study of the affected areas in smokers might better guide future research into the pathogenesis of chronic smoking.Objective:To assess the alterations in regional homogeneity of resting-state brain activity in chronic cigarette smokers. Methods:In this study,45 otherwise healthy smokers and 44 healthy control subjects being imaged with BOLD fMRI and analyzed with the ReHo method. Results: Compared with healthy controls, decreased ReHo was found in smokers in the right inferior frontal gyrus and increased ReHo was found in left superior parietal lobule (p<0.05, voxel=10, cluster-level corrected). Conclusions:To our knowdge, this is the first time to find the changes of the resting-state of brain activity in patients with ketamine dependence. Our findings indicated abnormal brain activity was distributed frontal cortex in patients with ketamine dependence during resting state. Objective:To assess the similarities and differences of cue-induced craving between ketamine user, smokers and healthy controls. Methods: Using block (ketamine-related, smoking-related and sex-related clips) design fMRI to aseess the brain acticities during different cue-induced craving in 41ketamine dependent subjects,45 smokers and 44 drug free healthy volunteers. Results:As for ketamine related cue, ketamine dependent subject showed brain activity changes; there is no difference between smokers and controls. As for smoking related cue, smokers showed higher brain activities than ketamine users and controls. As for sex related cue, ketamine users showed lower brain activity than smokers and controls; there is no difference between smokers and controls. Conclusions:The findings suggest that ketamine and smoking cue-elicited craving induced multiple brain regions’ activity which associated with the neurophthology of addiction.更多还原