首發(fā)抑郁癥功能磁共振靜息態(tài)腦網(wǎng)絡(luò)與5-HTTLPR相關(guān)性研究
發(fā)布時間：2018-08-28 19:52
【摘要】：背景和目的抑郁癥是一種十分常見的精神類疾病,臨床癥狀復(fù)雜多樣,可有持續(xù)的情緒狀態(tài)、認(rèn)知行為、生理學(xué)行為和社會行為的異常改變,具有高發(fā)病率、高自殺率、高致殘率及低診斷率的特點(diǎn)。抑郁癥的發(fā)病機(jī)制比較復(fù)雜,目前多認(rèn)為是生物化學(xué)因素、遺傳因素、環(huán)境因素和社會心理因素等多種方面共同作用的結(jié)果。5-羥色胺轉(zhuǎn)運(yùn)體基因啟動子區(qū)(5-hydroxynyptamine transporter gene linked polymorphic region,5-HTTLPR)多態(tài)性與抑郁癥的關(guān)系一直是研究熱點(diǎn)之一。功能磁共振成像技術(shù)(functional magnetic resonance imaging,fMRI)為探索抑郁癥病因及發(fā)病機(jī)制提供了新的方向。獨(dú)立成分分析(independent component analysis,ICA)是一種分析靜息態(tài)腦網(wǎng)絡(luò)功能連接的常用方法。本研究從基因影像學(xué)的角度,利用fMRI-ICA的方法,旨在探討首發(fā)未用藥抑郁癥患者的靜息態(tài)腦網(wǎng)絡(luò)的功能連接改變以及5-HTTLPR對腦網(wǎng)絡(luò)的影響。材料與方法采用GE Discovery 750 3.0 T MRI掃描儀對93例首發(fā)的未用藥抑郁癥患者和70例性別、年齡、受教育程度相匹配的正常對照者進(jìn)行常規(guī)MRI、3D結(jié)構(gòu)像和靜息態(tài)fMRI數(shù)據(jù)采集,其中2例首發(fā)抑郁癥患者和1例正常對照者因頭動大于設(shè)置閾值被剔除。同時對其中58例首發(fā)抑郁癥患者和39例正常對照進(jìn)行5-HTTLPR基因型的檢測。靜息態(tài)fMRI數(shù)據(jù)采用基于Matlab平臺的DPARSFA軟件進(jìn)行預(yù)處理,獨(dú)立成分分析采用基于Matlab平臺的GIFT軟件進(jìn)行腦網(wǎng)絡(luò)成分的提取。統(tǒng)計(jì)學(xué)分析采用基于Matlab平臺的SPM軟件,首發(fā)抑郁癥組與正常對照組之間靜息態(tài)網(wǎng)絡(luò)比較采用雙樣本t檢驗(yàn)(AlpahSim矯正,P0.001)。兩組中不同基因型功能網(wǎng)絡(luò)內(nèi)異常腦區(qū)的比較采用兩因素方差分析,存在顯著性差異時采用事后多重比較(post-hoc test)進(jìn)行兩兩比較(AlpahSim矯正,P0.001)。結(jié)果首發(fā)抑郁癥組與對照組5-HTTLPR基因型分布頻率差異無統(tǒng)計(jì)學(xué)意義(P0.05),病例組S等位基因頻率高于對照組,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。通過ICA方法共提取出13個靜息態(tài)腦網(wǎng)絡(luò):前默認(rèn)網(wǎng)絡(luò)、后默認(rèn)網(wǎng)絡(luò)、突顯網(wǎng)絡(luò)、中央執(zhí)行網(wǎng)絡(luò)、背側(cè)注意網(wǎng)絡(luò)、感覺運(yùn)動網(wǎng)絡(luò)、聽覺網(wǎng)絡(luò)、外側(cè)視覺網(wǎng)絡(luò)、內(nèi)側(cè)視覺網(wǎng)絡(luò)、枕極視覺網(wǎng)絡(luò)、語言網(wǎng)絡(luò)、左側(cè)額頂網(wǎng)絡(luò)和右側(cè)額頂網(wǎng)絡(luò)。靜息態(tài)腦網(wǎng)絡(luò)內(nèi)功能連接的比較結(jié)果:(1)前默認(rèn)網(wǎng)絡(luò):與對照組相比,首發(fā)抑郁癥組患者前默認(rèn)網(wǎng)絡(luò)內(nèi)右側(cè)額上回的功能連接減弱(t=-3.4291);病例組SS基因型較SL+LL基因型患者左側(cè)前扣帶回的功能連接減弱(t=-3.5735)。(2)后默認(rèn)網(wǎng)絡(luò):與對照組相比,首發(fā)抑郁癥組患者后默認(rèn)網(wǎng)絡(luò)內(nèi)左側(cè)楔前葉的功能連接增強(qiáng)(t=2.962);病例組SS基因型較SL+LL基因型患者左側(cè)后扣帶回的功能連接增強(qiáng)(t=2.9896),右側(cè)頂下小葉的功能連接減弱(t=-3.3036)(3)突顯網(wǎng)絡(luò):與對照組相比,首發(fā)抑郁癥組患者突顯網(wǎng)絡(luò)右側(cè)額中回的功能連接減弱(t=-3.6232);病例組SS基因型較SL+LL基因型患者存在右側(cè)額上回(t=-3.8313)、左側(cè)額中回(t=-3.7324)的功能連接減弱。(4)中央執(zhí)行網(wǎng)絡(luò):與對照組相比,首發(fā)抑郁癥組患者中央執(zhí)行網(wǎng)絡(luò)左側(cè)額中回的功能連接減弱(t=-4.6137),左側(cè)頂下小葉的功能連接增強(qiáng)(t=3.2683);病例組SS基因型較SL+LL基因型患者左側(cè)顳中回的功能連接增強(qiáng)(t=3.7654)。(5)背側(cè)注意網(wǎng)絡(luò):與對照組相比,首發(fā)抑郁癥組患者背側(cè)注意網(wǎng)絡(luò)中右側(cè)頂上小葉存在功能連接增強(qiáng)腦區(qū)(t=3.4507)及減弱腦區(qū)(t=-3.6394),各基因型組間腦區(qū)差異無統(tǒng)計(jì)學(xué)意義。(6)感覺運(yùn)動網(wǎng)絡(luò):與對照組相比,首發(fā)抑郁癥組患者感覺運(yùn)動網(wǎng)絡(luò)右側(cè)中央后回的功能連接減弱(t=-4.3926);病例組SS基因型較SL+LL基因型患者右側(cè)中央后回的功能連接增強(qiáng)(t=4.4873)。(7)聽覺網(wǎng)絡(luò):與對照組相比,首發(fā)抑郁癥組患者聽覺網(wǎng)絡(luò)右側(cè)(t=-3.7995)及左側(cè)豆?fàn)詈说墓δ苓B接減弱(t=-4.0086),各基因型組間差異腦區(qū)無統(tǒng)計(jì)學(xué)意義。(8)外側(cè)視覺網(wǎng)絡(luò):與對照組相比,首發(fā)抑郁癥組患者外側(cè)視覺網(wǎng)絡(luò)右側(cè)楔葉的功能連接增強(qiáng)(t=3.2075);病例組SS基因型較SL+LL基因型患者右側(cè)顳上回的功能連接增強(qiáng)(t=3.2641)。(9)內(nèi)側(cè)視覺網(wǎng)絡(luò):首發(fā)抑郁癥組與對照組以及各基因型組間差異腦區(qū)無統(tǒng)計(jì)學(xué)意義。(10)枕極視覺網(wǎng)絡(luò):與對照組相比,首發(fā)抑郁癥組患者枕極視覺網(wǎng)絡(luò)右側(cè)楔葉的功能連接增強(qiáng)(t=3.5478),各基因型組間差異腦區(qū)無統(tǒng)計(jì)學(xué)意義。(11)語言網(wǎng)絡(luò):與對照組相比,首發(fā)抑郁癥組患者語言網(wǎng)絡(luò)右側(cè)楔前葉功能連接增強(qiáng)(t=3.7834);病例組SS基因型較SL+LL基因型患者左側(cè)顳中回功能連接減弱(t=-3.6036)。(12)左側(cè)額頂網(wǎng)絡(luò):與對照組相比,首發(fā)抑郁癥組患者左側(cè)額頂網(wǎng)絡(luò)存在左側(cè)額中回的功能連接減弱(t=-3.1384),各基因型組間差異腦區(qū)無統(tǒng)計(jì)學(xué)意義。(13)右側(cè)額頂網(wǎng)絡(luò):與對照組相比,首發(fā)抑郁癥組患者右側(cè)額頂網(wǎng)絡(luò)右側(cè)額中回的功能連接減弱(t=-3.937);各基因型組間差異腦區(qū)無統(tǒng)計(jì)學(xué)意義。結(jié)論5-HTTLPR的S等位基因可能為抑郁癥患者的易感基因;首發(fā)抑郁癥患者存在多個靜息態(tài)腦網(wǎng)絡(luò)功能連接異常;5-HTTLPR可能通過5-羥色胺轉(zhuǎn)運(yùn)體的表達(dá)影響抑郁癥腦網(wǎng)絡(luò)的功能連接。
[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.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R445.2;R749.4
，
本文編號：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.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R445.2;R749.4
，
本文編號：2210441
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