青少年广泛性焦虑障碍患者脑结构与脑功能特点的研究

发布时间：2018-04-10 14:46

本文选题：广泛性焦虑障碍 + 磁共振成像　；参考：《中南大学》2013年博士论文

【摘要】：目的：广泛性焦虑障碍(Generalized Anxiety Disorder, GAD)是一种很常见的焦虑障碍,然而目前为止有关其神经病理生理学机制的研究相对较少。本研究的目的包括三个方面：1.采用高分辨结构磁共振成像(Structural Magnetic Resonance Imaging, sMRI)技术和基于体素的形态测量(Voxel-Based Morphometry, VBM)方法对首发未治疗的青少年GAD患者脑灰质体积的异常进行研究,同时探讨性别及儿童虐待因素对GAD患者脑灰质体积的影响。2.使用弥散张量成像(Diffusion Tensor Imaging, DTI)技术和基于体素的分析(Voxel-Based Analysis, VBA)方法对首发未治疗的青少年GAD患者脑白质完整性的异常进行研究,同时探讨性别及儿童虐待因素对GAD患者脑白质完整性的影响。3.使用功能磁共振成像(Functional Magnetic Resonance Imaging, fMRI)技术和点探测任务探索首发未治疗的青少年GAD患者选择性注意偏倚的特点及可能的与之相关的脑神经病理学机制。方法：采用儿童焦虑性情绪障碍筛查表(The Screen for Child Anxiety Related Emotional Disorders,SCARED)和学龄期儿童情感障碍和精神分裂症半定式诊断诊断量表(The Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime,K-S ADS-PL)进行筛查和评估,入组符合美国《精神障碍诊断与统计手册》第4版(Diagnostic and Statistical Manual Version-Ⅳ, DSM-Ⅳ) GAD诊断标准的首发青少年患者以及与之在性别、年龄、文化程度上相匹配的青少年健康对照。所有入组的研究对象完成认知测验和儿童创伤问卷(The Childhood Trauma Questionnaire, CTQ)的评估。患者组同时完成贝克抑郁自评问卷(Beck Depression Inventory, BDI)和宾夕法尼亚焦虑问卷(The Penn State Worry Questionnaire, PSWQ)的评估。随后,两组研究对象分别完成磁共振扫描,包括sMRI、DTI和fMRI。在完成fMRI扫描时,要求研究对象同时完成点探测任务。最后,采用统计参数图(Statistical Parametric Mapping, SPM)软件和统计产品与服务解决方案(Statistical Product and Service solutions, SPSS)软件等进行数据的分析和处理。结果：1.完成高分辨率sMRI的青少年GAD患者30例,青少年健康对照27例。排除头动影响所致图像质量问题以及量表资料不全的研究对象,最终26例青少年GAD患者和25例健康对照被纳入统计分析。结果显示,与健康对照组相比,青少年GAD患者显示出右侧壳核、右侧岛叶、左侧舌状回和左侧海马体积明显增加。将性别作为分层因素后的结果显示,右侧壳核存在显著的诊断主效应,性别主效应主要存在于左侧楔前叶/后扣带皮质、双侧尾状核、右侧眶额叶皮质和左侧小脑后叶,无任何脑区存在明显的诊断-性别交互作用。对性别主效应做进一步的比较显示,男性左侧楔前叶/后扣带皮质明显大于女性,而女性双侧尾状核、右侧眶额叶皮质和左侧小脑后叶灰质体积大于男性。将有无虐待作为分层因素后结果显示,右侧壳核存在显著的诊断主效应,未发现明显的虐待主效应,诊断-虐待交互作用主要存在于左侧丘脑。对具有诊断-虐待交互作用的脑区进行进一步分析显示,仅有经历儿童虐待的青少年GAD患者显示出左侧丘脑体积的增大,同时发现仅在GAD患者中儿童创伤问卷总评分与左侧丘脑平均体积呈正相关。 2.完成DTI的青少年GAD患者28例,青少年健康对照27例。排除头动影响导致图像质量问题以及量表资料不全的研究对象,最终25例青少年GAD患者和24例健康对照被纳入统计分析。结果显示,与健康对照相比,青少年GAD患者双侧额叶白质以及右侧枕叶白质FA显著降低,未发现FA增加的脑区。将性别作为分层因素后结果显示,诊断主效应存在于双侧额叶白质和右侧枕叶白质,未发现任何脑区存在明显的性别主效应以及诊断-性别交互作用。将有无虐待作为分层因素后结果显示,诊断主效应存在于双侧额叶白质和右侧枕叶白质,虐待主效应存在于右侧顶叶下白质,并未发现任何脑区存在诊断-虐待交互作用。进一步分析虐待主效应显示经历过儿童期虐待的个体较未经历儿童虐待的个体顶叶白质FA增加。 3.完成fMRI的青少年GAD患者28例,青少年健康对照26例。排除头动影响导致图像质量问题以及量表资料不全的研究对象和未配合完成实验任务的研究对象,最终23例青少年GAD患者和21例健康对照被纳入统计分析。行为学结果显示,青少年GAD患者平均反应时间长于健康对照组；所有研究对象对包含危险图片任务的平均反应时间显著长于对包含高兴图片任务的平均反应时间；青少年GAD患者对危险图片的脱离指数显著大于0,且明显大于对照组对危险图片的脱离指数。功能磁共振结果显示,青少年GAD患者相对于健康对照在完成包含危险图片的任务时,表现出左侧背外侧前额叶皮质、右侧前扣带皮质和左侧颞中回活动的减少,且左侧背外侧前额叶皮质激活程度与焦虑症状呈负相关关系。结论：1.本研究支持GAD的发生是基于皮层及皮层下结构相互作用异常的假说。额叶和壳核均可能参与GAD发生的神经环路基础。 2.脑结构的性别差异主要反映在脑灰质体积上,脑白质完整性并无性别差异。然而GAD脑灰质体积的异常并不受性别因素的影响。 3.儿童虐待因素与青少年GAD患者相关的脑区可能是丘脑。经历过儿童虐待的个体顶叶的异常提示这些个体可能存在对环境中信息的过分加工,从而增加发生精神障碍的风险。 4.青少年GAD患者对危险刺激存在选择性注意偏倚,主要表现为对危险刺激的注意解除困难,推测其神经病理学机制可能涉及前额叶皮质包括前扣带回等高级皮层结构的调控异常。
[Abstract]:Objective : Generalized anxiety disorder ( GAD ) is a common anxiety disorder . The study aims to study the abnormal brain gray volume in GAD patients with GAD by using high resolution magnetic resonance imaging ( sMRI ) technique and voxel - based morphological measurement ( VBM ) .

Methods : The screening and evaluation were performed on The Screen for Child Anxiety Related Disorders ( SCARED ) and School Age Children - Present and Lifetime , K - S ADS - PL . SPSS ) software and other data analysis and processing .

Results : 1 . There were 30 adolescent GAD patients with high resolution sMRI , 27 adolescents with healthy controls . The results showed that there was a significant difference in diagnosis - sex interaction between the right shell nucleus , the right island lobe , the left posterior lobe cortex and the left cerebellum .

2 . There were 28 adolescent GAD patients with DTI and 27 adolescent health controls . The results showed that there was no obvious gender - dominant effect in the bilateral frontal and right occipital lobes in adolescents with GAD . The results showed that the main effect was found in the white matter of bilateral frontal lobe and right occipital lobe . The main effect of treatment was found in the white matter of both frontal and right occipital lobes .

The results showed that the average reaction time of GAD in adolescents was longer than that of healthy control group .
The average reaction time for all study subjects to the task containing the dangerous picture was significantly longer than the average reaction time for the task containing the happy picture task ;
Results of functional magnetic resonance showed that adolescents with GAD showed a negative correlation with anxiety symptoms in the anterior frontal lobe cortex , the right anterior buckle cortex and the left temporal gyrus compared to healthy controls .

Conclusion : 1 . The development of GAD is based on the hypothesis that the interaction between cortex and subcortical structures is abnormal . Both frontal lobe and shell nucleus may be involved in the neuro - loop basis of GAD .

2 . The sex difference of the brain structure is mainly reflected in the brain gray matter volume , the white matter integrity of the brain does not have sex difference . However , the abnormality of the gray matter volume of GAD is not influenced by gender .

3 . Child abuse factors may be related to adolescent GAD patients , which may be the thalamus . Exceptions to individual parietal lobes experienced by child abuse suggest that these individuals may have excessive processing of information in the environment , thereby increasing the risk of mental disorders .

4 . The selective attention bias exists in the patients with GAD , which is mainly manifested by the difficulty of paying attention to the dangerous stimulation , and it is speculated that the neuropathology mechanism may involve the abnormal regulation of the advanced cortical structures such as the frontal cortex including the anterior buckle .

【学位授予单位】：中南大学
【学位级别】：博士
【学位授予年份】：2013
【分类号】：R445.2;R749.72

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