首发抑郁症功能磁共振静息态脑网络与5-HTTLPR相关性研究
发布时间：2018-08-28 19:52
【摘要】：背景和目的抑郁症是一种十分常见的精神类疾病,临床症状复杂多样,可有持续的情绪状态、认知行为、生理学行为和社会行为的异常改变,具有高发病率、高自杀率、高致残率及低诊断率的特点。抑郁症的发病机制比较复杂,目前多认为是生物化学因素、遗传因素、环境因素和社会心理因素等多种方面共同作用的结果。5-羟色胺转运体基因启动子区(5-hydroxynyptamine transporter gene linked polymorphic region,5-HTTLPR)多态性与抑郁症的关系一直是研究热点之一。功能磁共振成像技术(functional magnetic resonance imaging,fMRI)为探索抑郁症病因及发病机制提供了新的方向。独立成分分析(independent component analysis,ICA)是一种分析静息态脑网络功能连接的常用方法。本研究从基因影像学的角度,利用fMRI-ICA的方法,旨在探讨首发未用药抑郁症患者的静息态脑网络的功能连接改变以及5-HTTLPR对脑网络的影响。材料与方法采用GE Discovery 750 3.0 T MRI扫描仪对93例首发的未用药抑郁症患者和70例性别、年龄、受教育程度相匹配的正常对照者进行常规MRI、3D结构像和静息态fMRI数据采集,其中2例首发抑郁症患者和1例正常对照者因头动大于设置阈值被剔除。同时对其中58例首发抑郁症患者和39例正常对照进行5-HTTLPR基因型的检测。静息态fMRI数据采用基于Matlab平台的DPARSFA软件进行预处理,独立成分分析采用基于Matlab平台的GIFT软件进行脑网络成分的提取。统计学分析采用基于Matlab平台的SPM软件,首发抑郁症组与正常对照组之间静息态网络比较采用双样本t检验(AlpahSim矫正,P0.001)。两组中不同基因型功能网络内异常脑区的比较采用两因素方差分析,存在显著性差异时采用事后多重比较(post-hoc test)进行两两比较(AlpahSim矫正,P0.001)。结果首发抑郁症组与对照组5-HTTLPR基因型分布频率差异无统计学意义(P0.05),病例组S等位基因频率高于对照组,差异有统计学意义(P0.05)。通过ICA方法共提取出13个静息态脑网络:前默认网络、后默认网络、突显网络、中央执行网络、背侧注意网络、感觉运动网络、听觉网络、外侧视觉网络、内侧视觉网络、枕极视觉网络、语言网络、左侧额顶网络和右侧额顶网络。静息态脑网络内功能连接的比较结果:(1)前默认网络:与对照组相比,首发抑郁症组患者前默认网络内右侧额上回的功能连接减弱(t=-3.4291);病例组SS基因型较SL+LL基因型患者左侧前扣带回的功能连接减弱(t=-3.5735)。(2)后默认网络:与对照组相比,首发抑郁症组患者后默认网络内左侧楔前叶的功能连接增强(t=2.962);病例组SS基因型较SL+LL基因型患者左侧后扣带回的功能连接增强(t=2.9896),右侧顶下小叶的功能连接减弱(t=-3.3036)(3)突显网络:与对照组相比,首发抑郁症组患者突显网络右侧额中回的功能连接减弱(t=-3.6232);病例组SS基因型较SL+LL基因型患者存在右侧额上回(t=-3.8313)、左侧额中回(t=-3.7324)的功能连接减弱。(4)中央执行网络:与对照组相比,首发抑郁症组患者中央执行网络左侧额中回的功能连接减弱(t=-4.6137),左侧顶下小叶的功能连接增强(t=3.2683);病例组SS基因型较SL+LL基因型患者左侧颞中回的功能连接增强(t=3.7654)。(5)背侧注意网络:与对照组相比,首发抑郁症组患者背侧注意网络中右侧顶上小叶存在功能连接增强脑区(t=3.4507)及减弱脑区(t=-3.6394),各基因型组间脑区差异无统计学意义。(6)感觉运动网络:与对照组相比,首发抑郁症组患者感觉运动网络右侧中央后回的功能连接减弱(t=-4.3926);病例组SS基因型较SL+LL基因型患者右侧中央后回的功能连接增强(t=4.4873)。(7)听觉网络:与对照组相比,首发抑郁症组患者听觉网络右侧(t=-3.7995)及左侧豆状核的功能连接减弱(t=-4.0086),各基因型组间差异脑区无统计学意义。(8)外侧视觉网络:与对照组相比,首发抑郁症组患者外侧视觉网络右侧楔叶的功能连接增强(t=3.2075);病例组SS基因型较SL+LL基因型患者右侧颞上回的功能连接增强(t=3.2641)。(9)内侧视觉网络:首发抑郁症组与对照组以及各基因型组间差异脑区无统计学意义。(10)枕极视觉网络:与对照组相比,首发抑郁症组患者枕极视觉网络右侧楔叶的功能连接增强(t=3.5478),各基因型组间差异脑区无统计学意义。(11)语言网络:与对照组相比,首发抑郁症组患者语言网络右侧楔前叶功能连接增强(t=3.7834);病例组SS基因型较SL+LL基因型患者左侧颞中回功能连接减弱(t=-3.6036)。(12)左侧额顶网络:与对照组相比,首发抑郁症组患者左侧额顶网络存在左侧额中回的功能连接减弱(t=-3.1384),各基因型组间差异脑区无统计学意义。(13)右侧额顶网络:与对照组相比,首发抑郁症组患者右侧额顶网络右侧额中回的功能连接减弱(t=-3.937);各基因型组间差异脑区无统计学意义。结论5-HTTLPR的S等位基因可能为抑郁症患者的易感基因;首发抑郁症患者存在多个静息态脑网络功能连接异常;5-HTTLPR可能通过5-羟色胺转运体的表达影响抑郁症脑网络的功能连接。
[Abstract]:BACKGROUND AND OBJECTIVE Depression is a very common psychiatric disorder with complex and varied clinical symptoms, including abnormal changes in emotional status, cognitive behavior, physiological behavior and social behavior, high morbidity, high suicide rate, high disability rate and low diagnostic rate. Functional magnetic resonance imaging (fMRI) is one of the hotspots in the study of the relationship between 5-HTTLPR polymorphism and depression. Functional magnetic resonance imaging (fMRI) provides a new direction for exploring the etiology and pathogenesis of depression. Independent component analysis (ICA) is a common method for analyzing functional connectivity of resting brain networks. Materials and Methods 93 patients with first-episode unused depression and 70 normal controls matched in sex, age and education were examined with GE Discovery 750 3.0 T MRI scanner for routine MRI, 3D imaging and static MRI. The resting fMRI data were preprocessed by DPARSFA software based on MATLAB platform, and the independent component scores were obtained. GIFT software based on MATLAB platform was used to extract the components of brain network. SPM software based on MATLAB platform was used for statistical analysis. The resting state network comparison between the first-episode depression group and the normal control group was performed by double-sample t-test (AlpahSim correction, P 0.001). The abnormal brain regions in different genotype functional networks were compared between the two groups. Results There was no significant difference in the genotype frequency of 5-HTTLPR between the first-episode depression group and the control group (P 0.05). The S allele frequency of the case group was higher than that of the control group (P 0.05). 13 resting brain networks were extracted by ICA: pre-default network, post-default network, highlight network, central executive network, dorsal attention network, sensorimotor network, auditory network, lateral visual network, medial visual network, occipital visual network, language network, left frontal-parietal network and right frontal-parietal network. The results of functional connectivity were as follows: (1) Pre-default network: compared with the control group, the functional connectivity of the right superior frontal gyrus in the first-episode depression group was weaker (t = - 3.4291); the functional connectivity of the left anterior cingulate gyrus in the case group with SS genotype was weaker than that in the SL + LL genotype (t = - 3.5735). (2) Post-default network: Compared with the control group, the first-episode depression was weaker. Functional connectivity of left anterior cuneiform lobe was enhanced (t = 2.962) in the default network after depression; functional connectivity of left posterior cingulate gyrus was enhanced (t = 2.9896) and functional connectivity of right inferior parietal lobe was weakened (t = - 3.3036) (3) in the SS genotype compared with the SL + LL genotype in the case group: The right prominence network was weakened in the first-episode depression group compared with the control group. Functional connectivity in the middle frontal gyrus was weakened (t = - 3.6232); functional connectivity in the right superior frontal gyrus (t = - 3.8313) and left middle frontal gyrus (t = - 3.7324) was weakened (t = - 4.6137) in the SS genotype compared with the SL + LL genotype in the case group. The functional connectivity of the left inferior parietal lobe was enhanced (t = 3.2683), and the functional connectivity of the left middle temporal gyrus was enhanced (t = 3.7654) in patients with SS genotype than in patients with SL + LL genotype. (5) Dorsal attention network: Compared with the control group, the right parietal lobe of the first-episode depression group had an enhanced functional connectivity area (t = 3.4507) and a decreased functional connectivity area (t = 3.4507). (t = - 3.6394), there was no significant difference between the genotypes. (6) Sensorimotor network: Compared with the control group, the functional connectivity of the right posterior central gyrus of the first-episode depression group was weakened (t = - 4.3926); the functional connectivity of the right posterior central gyrus of the patients with SS genotype was enhanced (t = 4.4873) compared with the SL + LL genotype. Network: Compared with the control group, the functional connectivity of the right auditory network (t = - 3.7995) and the left lenticular nucleus (t = - 4.0086) was weakened in the first-episode depression group, and there was no significant difference among the genotypes. (8) Lateral visual network: Compared with the control group, the functional connectivity of the right cuneiform lobe of the lateral visual network was enhanced in the first-episode depression group (t = 3.0086). (9) Medial visual network: There was no significant difference between the first-episode depression group and the control group, as well as between the genotypes. (10) Occipital visual network: Compared with the control group, the occipital visual network in the first-episode depression group was right wedge of occipital visual network. Language network: Compared with the control group, the functional connectivity of the right anterior cuneal lobe was enhanced in the first depression group (t = 3.7834); the functional connectivity of the left middle temporal gyrus was weakened in the case group (t = - 3.6036) compared with the SL + LL genotype. Fronto-parietal network: Compared with the control group, the left fronto-parietal network had weaker functional connectivity in the left middle frontal gyrus (t = - 3.1384), and there was no significant difference among genotypes. (13) Right fronto-parietal network: Compared with the control group, the right fronto-parietal network had weaker functional connectivity in the right middle frontal gyrus (t = - 3.1384). Conclusion The S allele of 5-HTTLPR may be a susceptible gene for depression patients; there are multiple resting state abnormalities in the functional connectivity of brain networks in first-episode depression patients; and the expression of 5-HTTLPR may affect the functional connectivity of depressive brain networks through the expression of serotonin transporters.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R445.2;R749.4
，
本文编号：2210441
[Abstract]:BACKGROUND AND OBJECTIVE Depression is a very common psychiatric disorder with complex and varied clinical symptoms, including abnormal changes in emotional status, cognitive behavior, physiological behavior and social behavior, high morbidity, high suicide rate, high disability rate and low diagnostic rate. Functional magnetic resonance imaging (fMRI) is one of the hotspots in the study of the relationship between 5-HTTLPR polymorphism and depression. Functional magnetic resonance imaging (fMRI) provides a new direction for exploring the etiology and pathogenesis of depression. Independent component analysis (ICA) is a common method for analyzing functional connectivity of resting brain networks. Materials and Methods 93 patients with first-episode unused depression and 70 normal controls matched in sex, age and education were examined with GE Discovery 750 3.0 T MRI scanner for routine MRI, 3D imaging and static MRI. The resting fMRI data were preprocessed by DPARSFA software based on MATLAB platform, and the independent component scores were obtained. GIFT software based on MATLAB platform was used to extract the components of brain network. SPM software based on MATLAB platform was used for statistical analysis. The resting state network comparison between the first-episode depression group and the normal control group was performed by double-sample t-test (AlpahSim correction, P 0.001). The abnormal brain regions in different genotype functional networks were compared between the two groups. Results There was no significant difference in the genotype frequency of 5-HTTLPR between the first-episode depression group and the control group (P 0.05). The S allele frequency of the case group was higher than that of the control group (P 0.05). 13 resting brain networks were extracted by ICA: pre-default network, post-default network, highlight network, central executive network, dorsal attention network, sensorimotor network, auditory network, lateral visual network, medial visual network, occipital visual network, language network, left frontal-parietal network and right frontal-parietal network. The results of functional connectivity were as follows: (1) Pre-default network: compared with the control group, the functional connectivity of the right superior frontal gyrus in the first-episode depression group was weaker (t = - 3.4291); the functional connectivity of the left anterior cingulate gyrus in the case group with SS genotype was weaker than that in the SL + LL genotype (t = - 3.5735). (2) Post-default network: Compared with the control group, the first-episode depression was weaker. Functional connectivity of left anterior cuneiform lobe was enhanced (t = 2.962) in the default network after depression; functional connectivity of left posterior cingulate gyrus was enhanced (t = 2.9896) and functional connectivity of right inferior parietal lobe was weakened (t = - 3.3036) (3) in the SS genotype compared with the SL + LL genotype in the case group: The right prominence network was weakened in the first-episode depression group compared with the control group. Functional connectivity in the middle frontal gyrus was weakened (t = - 3.6232); functional connectivity in the right superior frontal gyrus (t = - 3.8313) and left middle frontal gyrus (t = - 3.7324) was weakened (t = - 4.6137) in the SS genotype compared with the SL + LL genotype in the case group. The functional connectivity of the left inferior parietal lobe was enhanced (t = 3.2683), and the functional connectivity of the left middle temporal gyrus was enhanced (t = 3.7654) in patients with SS genotype than in patients with SL + LL genotype. (5) Dorsal attention network: Compared with the control group, the right parietal lobe of the first-episode depression group had an enhanced functional connectivity area (t = 3.4507) and a decreased functional connectivity area (t = 3.4507). (t = - 3.6394), there was no significant difference between the genotypes. (6) Sensorimotor network: Compared with the control group, the functional connectivity of the right posterior central gyrus of the first-episode depression group was weakened (t = - 4.3926); the functional connectivity of the right posterior central gyrus of the patients with SS genotype was enhanced (t = 4.4873) compared with the SL + LL genotype. Network: Compared with the control group, the functional connectivity of the right auditory network (t = - 3.7995) and the left lenticular nucleus (t = - 4.0086) was weakened in the first-episode depression group, and there was no significant difference among the genotypes. (8) Lateral visual network: Compared with the control group, the functional connectivity of the right cuneiform lobe of the lateral visual network was enhanced in the first-episode depression group (t = 3.0086). (9) Medial visual network: There was no significant difference between the first-episode depression group and the control group, as well as between the genotypes. (10) Occipital visual network: Compared with the control group, the occipital visual network in the first-episode depression group was right wedge of occipital visual network. Language network: Compared with the control group, the functional connectivity of the right anterior cuneal lobe was enhanced in the first depression group (t = 3.7834); the functional connectivity of the left middle temporal gyrus was weakened in the case group (t = - 3.6036) compared with the SL + LL genotype. Fronto-parietal network: Compared with the control group, the left fronto-parietal network had weaker functional connectivity in the left middle frontal gyrus (t = - 3.1384), and there was no significant difference among genotypes. (13) Right fronto-parietal network: Compared with the control group, the right fronto-parietal network had weaker functional connectivity in the right middle frontal gyrus (t = - 3.1384). Conclusion The S allele of 5-HTTLPR may be a susceptible gene for depression patients; there are multiple resting state abnormalities in the functional connectivity of brain networks in first-episode depression patients; and the expression of 5-HTTLPR may affect the functional connectivity of depressive brain networks through the expression of serotonin transporters.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R445.2;R749.4
，
本文编号：2210441
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