分享:
分享到微信朋友圈
X
基础研究
原发性失眠患者脑磁共振波谱成像研究
苏晓艳 赵莲萍 谢宇平 方燕燕 张文文 周丽雅 惠培林 王旭斌

Cite this article as: Su XY, Zhao LP, Xie YP, et al. Study on thecerebrum metabolism in PI patients using magnetic resonance spectroscopy[J]. Chin J Magn Reson Imaging, 2022, 13(2): 47-51.本文引用格式:苏晓艳, 赵莲萍, 谢宇平, 等. 原发性失眠患者脑磁共振波谱成像研究[J]. 磁共振成像, 2022, 13(2): 47-51. DOI:10.12015/issn.1674-8034.2022.02.010.


[摘要] 目的 研究原发性失眠(primary insomnia,PI)患者不同脑区(丘脑、海马、壳核)代谢特点。材料与方法 采用氢质子磁共振波谱成像技术检测38例PI患者(PI组)和39例健康对照者(healthy control,HC)组丘脑、海马区、壳核区的氮-乙酰基天门冬氨酸(N-acetyl-aspartate,NAA)、胆碱复合物(choline-containing compounds,Cho)和肌酸(creatine,Cr)浓度,并计算NAA/Cr和Cho/Cr。采用多导睡眠监测(polysomnography,PSG)技术监测客观睡眠参数;采用神经心理量表匹茨堡睡眠质量指数和睡眠严重程度指数评定所有受试者的主观睡眠质量和失眠严重程度;采用状态-特质焦虑量表(State-Trait Anxiety Inventory,STAI)和贝克抑郁量表(Beck Depression Inventory,BDI)评定受试者的焦虑及抑郁程度。结果 (1)代谢物浓度比较:与HC组对比,PI组左侧丘脑Cr、Cho浓度升高(P=0.040,P=0.007),右侧丘脑Cho浓度升高(P=0.039),双侧海马和壳核区的代谢物与对照组相比差异无统计学意义(P all>0.05)。(2)相关性:PI患者左侧丘脑NAA值与总睡眠时间、睡眠效率呈负相关(r=-0.384,P=0.017),左侧丘脑NAA/Cr值与REM%呈负相关(r=-0.387,P=0.016);右侧丘脑Cho/Cr值与SL%呈正相关(r=0.380,P=0.019),丘脑NAA、Cr、Cho、NAA/Cr、Cho/Cr值与各量表评分未见明显相关。PI患者左侧海马Cho值与ArI呈正相关(r=0.348,P=0.044);右侧海马Cho值(r=-0.334,P=0.047)、Cr值(r=-0.445,P=0.007)与BDI评分呈负相关。PI患者左侧壳核NAA值与N3%呈正相关(r=0.340,P=0.037);左侧壳核Cr值与特质焦虑量表(Trait Anxiety Inventory,TAI)呈正相关(r=0.447,P=0.005);左侧壳核NAA/Cr值与N1% (r=-0.344,P=0.047)、TAI评分(r=-0.521,P=0.001)、状态焦虑量表(State Anxiety Inventory,SAI)评分(r=-0.400,P=0.013)呈负相关;左侧壳核Cho/Cr与TAI评分(r=-0.527,P=0.001)、SAI评分(r=-0.434,P=0.007)呈负相关。组间差异的参数与各量表评分及PSG参数未见明显的相关性。结论 PI患者丘脑Cho及Cr代谢紊乱;客观睡眠影响丘脑区域代谢,而患者情绪障碍与海马和壳核区域的代谢有关。
[Abstract] Objective To study the cerebrum metabolism in patients with primary insomnia (PI).Materials and Methods Proton magnetic resonance spectroscopy technology was used to detect concentrations of N-acetyl-aspartate, choline-containing compounds and creatine in the thalamus, hippocampus and putamen of 38 PI patients (PI group) and 39 healthy controls (HC group), and NAA/Cr and Cho/Cr were calculated. Polysomnography (PSG) was used to measure objective sleep parameters. Assess sleep quality by fill in the form of the Pittsburgh sleep quality index and insomnia severity index; Assess sentiment by fill in the form of State-Trait Anxiety Inventory (STAI) and Beck Depression Inventory (BDI).Results (1) Comparison of metabolite concentration: compared with the HC group, the concentration of Cr and Cho in the left thalamus of PI group increased (P=0.040, P=0.007), the concentration of Cho in the right thalamus increased (P=0.039), bilateral hippocampus and shell The metabolites in the nuclear area were not different from the control group (Pall>0.05). (2) Correlation: The NAA value of the left thalamus in PI patients is negatively correlated with total sleep time and sleep efficiency (r=-0.384, P=0.017), and NAA/Cr value is negatively correlated with REM% (r=-0.387, P=0.016); right thalamus Cho/Cr value is positively correlated with SL% (r=0.380, P=0.019), There was no significant correlation between the thalamus NAA, Cr, Cho, NAA/Cr, Cho/Cr values and the scores of each scale. The Cho value of the left hippocampus of patients with insomnia is positively correlated with ArI (r=0.348, P=0.044); the Cho value of the right hippocampus (r=-0.334, P=0.047), Cr value (r=-0.445, P=0.007) and The BDI score was negatively correlated. The NAA value of the left putamen of PI was positively correlated with N3% (r=0.340, P=0.037); The Cr value of the left putamen is positively correlated with Trait Anxiety Inventory (TAI) (r=0.447, P=0.005); the NAA/Cr value of the left putamen is correlated with N1% (r=-0.344, P=0.047), TAI score (r=-0.521, P=0.001), State Anxiety Inventory (SAI) score (r=-0.400, P=0.013) is negatively correlated; Cho/Cr on the left putamen is negatively correlated with TAI score (r=-0.527, P=0.001) and SAI score (r=-0.434, P=0.007). There was no obvious correlation between the parameters of the differences between the groups and the scores of the various scales and PSG parameters.Conclusion The metabolism of Cho and Cr in the thalamus of PI patients is impaired. Objective sleep affects the metabolism of the thalamus. The patient's mood disorder is related to the metabolism of the hippocampus and putamen.
[关键词] 原发性失眠;氢质子磁共振波谱成像;代谢;丘脑;海马;壳核
[Keywords] primary insomnia;proton magnetic resonance spectroscopy;metabolism;thalamus;hippocampus;putamen

苏晓艳 1   赵莲萍 2   谢宇平 1*   方燕燕 2   张文文 2   周丽雅 3   惠培林 1   王旭斌 1  

1 甘肃省人民医院睡眠医学中心,兰州 730000

2 甘肃省人民医院放射科,兰州 730000

3 甘肃省人民医院脑电图室,兰州 730000

谢宇平,E-mail:xyp5894@163.com

作者利益冲突声明:全部作者均申明无利益冲突。


基金项目: 国家自然科学基金 81560228 甘肃省卫生行业科研计划项目 GSWSKY-2019-88 甘肃省人民医院院内科研基金项目 21GSSYB-25
收稿日期:2021-08-11
接受日期:2022-01-30
中图分类号:R445.2  R256.23 
文献标识码:A
DOI: 10.12015/issn.1674-8034.2022.02.010
本文引用格式:苏晓艳, 赵莲萍, 谢宇平, 等. 原发性失眠患者脑磁共振波谱成像研究[J]. 磁共振成像, 2022, 13(2): 47-51. DOI:10.12015/issn.1674-8034.2022.02.010

       原发性失眠(primary insomnia,PI)是指以失眠为几乎唯一的症状,睡眠时间少于6 h/天,上述睡眠障碍至少3晚/周并持续3个月以上[1]。大脑在睡眠中起重要作用,其中丘脑在清醒与睡眠的转换中起重要作用,研究已经证明丘脑神经元与睡眠纺锤波的产生以及睡眠和觉醒的转换调节有关[2]。海马与睡眠关系密切[3],且与记忆储存有关,PI患者表现出记忆缺陷[4]。有研究发现PI患者海马、丘脑、前额叶等区域[5]神经解剖发生改变,双侧海马体积明显减小[6]。但是,PI患者大脑代谢产物有无改变,与失眠的发生发展有无关联,目前这方面的研究较少。仅国内有研究发现PI患者左、右两侧额叶氮-乙酰天门冬氨酸(N-acetylaspartate,NAA)/肌酸(creatine,Cr)水平均低于正常健康对照(healthy control,HC)组;右侧额叶胆碱复合物(choline-containing compounds,Cho)、Cho/Cr水平均高于HC组,从而认为双侧额叶NAA和右侧额叶Cho均可能与PI的发病机制有关[7]。氢质子磁共振波谱成像(proton magnetic resonance spectroscopy,1H-MRS)能够无创伤测定活体特定组织区域神经生化物质的浓度。因此,为填补此空白,本研究采用多体素1H-MRS技术半定量研究未经药物治疗的PI患者双侧丘脑、海马和壳核区NAA、Cho和Cr浓度,用以探讨PI的发病机制,为PI的机制研究补充内容。

1 资料与方法

1.1 研究对象

       连续性纳入2018年6月至2021年6月就诊于甘肃省睡眠医学中心的PI患者和广告招募的PI患者,并通过广告招募年龄、性别匹配的健康志愿者作为对照组,保证2组成员无血缘关系。所有受试者第一天22:00由同一个专业睡眠技师进行多导睡眠监测(polysomnography,PSG),次日7:00结束,第二天22:00行颅脑1H-MRS扫描。

       PI组纳入标准:(1)符合《美国精神障碍诊断与统计手册》第5版的PI诊断标准[1];(2)小学以上文化,汉族,右利手;(3)年龄18~65岁。HC组纳入标准:(1)睡眠质量良好,近2周内无熬夜;(2)小学以上文化,汉族,右利手;(3)年龄18~65岁。排除标准(两组均适用):(1)由于其他精神障碍以及酒精或药物、毒物等引起的继发性失眠;(2)伴有严重躯体疾病患者;(3)近期遭受重大心理刺激应激性失眠者;(4) PSG监测结果显示主观性失眠患者;(5) 呼吸暂停低氧指数(apnea hypopnea index,AHI)>15者;(6)头部外伤史者。

       对所有受试者的睡眠质量及情绪障碍等进行以下量表评估:(1)匹兹堡睡眠质量指数量表(Pittsburgh Sleep Quality Index,PSQI);(2)失眠严重程度指数量表(Insomnia Severity Index,ISI);(3)状态-特质焦虑量表(State-Trait Anxiety Inventory,STAI);(4)贝克抑郁量表(Beck Depression Inventory,BDI)。

       本研究为前瞻性研究,经由甘肃省人民医院院伦理委员会批准(批准文号:sy1120150043),且所有受试者均签署了知情同意书。

1.2 研究方法

       PSG监测、分图及各项数据计算方法:睡眠监测使用多导睡眠监测记录仪(Alice5型,美国飞利浦公司),由接受过专业培训的睡眠技师连接导联并分图,睡眠分期按照美国睡眠医学会颁布的《睡眠及其相关事件判读手册(2.3版)》[8]的标准执行。其中,总睡眠时间(total sleep time,TST)=卧床时间­总醒觉时间;睡眠潜伏时间(sleep latency,SL)=(入睡记录帧­熄灯记录帧)/2;睡眠效率(sleep efficiency,SE)=(总睡眠时间/卧床时间)×100;脑电觉醒反应指数(EEG Arousal Response Index,ArI)=脑电觉醒反应总数×60/总睡眠时间;各期睡眠百分比(N1、N2、N3、REM%)=(N1、N2、N3、REM期睡眠时间/总睡眠时间)×100。

       1H-MRS数据采集:所有受试者安排睡眠监测次日22:00进行1H-MRS扫描,采用3.0 T磁共振(MAGNETOMSkyra,Siemens Healthcare,Erlangen,Germany)进行多体素2D 1H-MRS扫描。扫描时受试者静息闭眼但保持清醒。选择丘脑、海马、壳核为感兴趣区(图1)。所有操作采用双盲设计,操作医师/审核医师及志愿者均不清楚当前扫描志愿者所入的组别。所有扫描由同一名经验丰富的影像科主治医师操作,扫描后由同一名影像科副主任医师审核。成像参数:频率编码方向A/P;发射频率10;相位10;层厚10 mm;间隔10 mm;视野为24 cm×24 cm;TR/TE为1000 ms/144 ms;矩阵18×18。扫描时间5 min 28 s。

       MRS数据分析:使用美国通用公司ADW 4.5工作站Functool软件进行后处理,测定代谢物NAA、Cho和Cr的相对水平,并计算NAA/Cr和Cho/Cr比值。

图1  1H-MRS扫描区域。1A:丘脑;1B:海马区;1C:壳核区。
Fig. 1  1H-MRS scanning area. 1A: thalamus; 1B: hippocampus area; 1C: putamen area.

1.3 统计分析

       运用IBM SPSS 21.0统计软件进行统计分析。P<0.05为有统计学意义。将测量到的波谱数据(定量资料)进行正态性及方差齐性检验。对本研究中所有量表得分、PSG数据和丘脑、海马、壳核区NAA、Cr、Cho、NAA/Cr、Cho/Cr数据分析,若满足正态性及方差齐性,则PI组和HC组间比较采用独立样本t检验。若不满足正态性及方差齐性,则使用Wilcoxon秩和检验进行数据分析。检验水准α=0.05,双侧检验。NAA、Cr、Cho、NAA/Cr、Cho/Cr和PSQI、ISI、状态焦虑量表(State Anxiety Inventory,SAI)、特质焦虑量表(Trait Anxiety Inventory,TAI)、BDI评分相关性,以及和PSG数据的相关性采用Pearson相关分析。相关系数r绝对值越大,相关性越强,相关强度范围:0.8≤|r|<1.0时极强相关,0.6≤|r|<0.8时较强相关,0.4≤|r|<0.6时中等相关,0.2≤|r|<0.4时较弱相关,0≤|r|<0.2极弱相关或无相关。

2 结果

2.1 基线数据

       数据处理时PI组2人、HC组1人因MRS扫描时部分数据缺失而剔除,最终收集PI组38人,HC组39人,PI组与HC组年龄、性别、BMI相比较,差异无统计学意义(P>0.05);ISI、PSQI、BDI、TAI、SAI量表评分差异有统计学意义(P<0.05) (表1)。

表1  PI组和HC组基线资料
Tab. 1  Baseline data of PI group and HC group

2.2 PI患者睡眠特点

       PI患者存在入睡困难[SL=(92.87±45.82) min],总睡眠时间少[TST=(282.07±47.13) min],睡眠效率低下(SE=52.24%±8.73%),夜间反复觉醒[ArI=(13.91±5.84) 次/h]。

2.3 1H-MRS扫描结果

2.3.1 丘脑1 H-MRS扫描结果

       PI组左侧丘脑Cr、Cho值及右侧丘脑Cho值高于HC组(P<0.05),均表现为浓度高于正常组;而双侧丘脑NAA、NAA/Cr、Cho/Cr值以及右侧丘脑Cr值差异无统计学意义(P>0.05) (表2)。

表2  丘脑1H-MRS扫描结果
Tab. 2  1H-MRS scan results of thalamus

2.3.2 海马区1H-MRS扫描结果

       与HC组相比,PI组双侧海马NAA、Cr、Cho、NAA/Cr、Cho/Cr值差异无统计学意义(P>0.05) (表3)。

表3  海马区1H-MRS扫描结果
Tab. 3  Hippocampal 1 H-MRS scan results

2.3.3 壳核区1H-MRS扫描结果

       与HC组相比,PI组双侧壳核NAA、Cr、Cho、NAA/Cr、Cho/Cr值差异无统计学意义(P>0.05) (表4)。

表4  壳核区1H-MRS扫描结果
Tab. 4  Putamen 1H-MRS scan results

2.4 大脑各区域与睡眠的相关性分析

       (1)丘脑代谢与睡眠:失眠患者左侧丘脑NAA值与TST、SE%负相关(r=-0.384,P=0.017),左侧丘脑NAA/Cr值与REM%呈负相关(r=-0.387,P=0.016),右侧丘脑Cho/Cr值与SL呈正相关(r=0.380,P=0.019),丘脑NAA、Cr、Cho、NAA/Cr、Cho/Cr值与各量表评分未见明显相关。

       (2)海马代谢与睡眠:失眠患者左侧海马Cho值与ArI呈正相关(r=0.348,P=0.044);右侧海马Cho值(r=-0.334,P=0.047)、Cr值(r=-0.445,P=0.007)与BDI评分呈负相关。

       (3)壳核代谢与睡眠:失眠患者左侧壳核NAA值与N3%呈正相关(r=0.340,P=0.037);左侧壳核Cr值与TAI呈正相关(r=0.447,P=0.005);左侧壳核NAA/Cr值与N1%(r=-0.344,P=0.047)、TAI评分(r=-0.521,P=0.001)、SAI评分(r=-0.400,P=0.013)呈负相关;左侧壳核Cho/Cr与TAI评分(r=-0.527,P=0.001)、SAI评分(r=-0.434,P=0.007)呈负相关。

3 讨论

       本研究使用1H-MRS技术对38名PI患者和39名HC志愿者进行丘脑、海马区、壳核区扫描,结果显示:丘脑Cho浓度PI组左右两侧均高于HC组;左侧丘脑Cr浓度PI组高于HC组。而海马及壳核NAA、Cr、Cho、NAA/Cr、Cho/Cr未见明显差异。目前国内外无类似丘脑、海马及壳核的代谢研究。本研究进一步对PI患者丘脑、海马、壳核各脑区代谢物NAA、Cr、Cho及NAA/Cr、Cho/Cr与睡眠监测相关参数及各量表评分进行相关性分析。结果发现:PI患者PSG监测SE%低者丘脑NAA浓度高,REM%低者左侧丘脑NAA/Cr越高,N3%多者左侧壳核NAA浓度高,N1%少者左侧壳核NAA/Cr高,SE%高者右侧Cho/Cr越高,PSG监测显示睡眠质量较好者右侧丘脑NAA/Cr越高,夜间ArI高者左侧海马Cho浓度高,BDI低者右侧海马Cho、Cr浓度越高,TAI高者左侧壳核Cr浓度高,SAI及TAI低者左侧壳核NAA/Cr、Cho/Cr高。组间差异的参数与失眠各量表评分及PSG睡眠参数未见明显的相关性。因此认为,丘脑和壳核区域代谢物水平与睡眠结构有相关性;壳核和海马区域代谢物水平与失眠患者情绪相关性更明显。

3.1 PI患者大脑代谢特点

       由于PI发病率很高,加上急性失眠能达到50%[9],失眠会导致社交活动减少[10],认知能力(如记忆力、注意力和定向力)出现缺陷[11, 12],甚至引起重大安全事故,对全球经济造成巨大的损失,因此失眠得到国内外学者的重视。众多学者应用神经影像技术对PI患者的皮质[13]等各脑区代谢物及功能连接[14, 15, 16]等进行研究,结果显示失眠患者某些脑区结构(尾状核、伏隔核、后壳核、海马、丘脑和杏仁核区域等[17])、功能、代谢等出现异常。其中大部分代谢物研究集中在额叶和枕叶的γ-氨基丁酸(Gamma-aminobutyric acid,GABA),而结果对于GABA升高和降低并不统一[18, 19, 20, 21, 22]。国内学者采用GE 1.5 T Signa HD MR对所有研究对象额叶及海马进行头颅磁共振波谱扫描,结果发现,PI患者左、右两侧额叶NAA/Cr水平均低于正常HC组;右侧额叶Cho、Cho/Cr水平均高于HC组,从而认为双侧额叶NAA和右侧额叶Cho均可能与PI的发病机制有关[7]。本研究发现PI患者睡眠分期及睡眠效率等与丘脑区域代谢物Cho及Cr相关性明显,提示PI患者丘脑Cho及Cr代谢紊乱。

3.2 PI患者情绪与大脑代谢的关系

       临床中显见,长期失眠患者都伴随明显的情绪障碍。而情绪调节与丘脑、海马区密切相关,丘脑更是睡眠-觉醒障碍病理生理的主要区域[2],背侧纹状体由尾状核和壳核组成,其与丘脑紧密相连,是调节睡眠-觉醒的关键结构[23]。大鼠睡眠剥夺后海马神经元发生抑制[24]。PI患者的海马灰质体积显著减少,也有研究发现两组脑区海马体积无差异[25]。睡眠障碍患者存在大脑代谢异常[26],大脑代谢与情绪以及认知之间存在相关性[27, 28]。本研究发现:PI患者焦虑抑郁等情绪与海马和壳核区域的代谢有一定相关性。

       因此本文得出结论:PI患者丘脑Cho及Cr代谢紊乱,客观睡眠影响丘脑区域代谢,而患者情绪障碍主要影响到海马和壳核区域的代谢。

[1]
美国精神医学学会编著(美).张道龙等 DOI: . 精神障碍诊断与统计手册: 案头参考书[M]. 北京: 北京大学出版社, 2014.
American Psychiatric Association. Zhang DL DOI: . The Diagnostic and Statistical Manual of Mental Disorders-5th Edition[M]. Beijing: Peking University Press, 2014.
[2]
Urbain N, Fourcaud-Trocmé N, Laheux S, et al. Brain-state-dependent modulation of neuronal firing and membrane potential dynamics in the somatosensory thalamus during natural sleep[J]. Cell Rep, 2019, 26(6): 1443-1457.e5. DOI: 10.1016/j.celrep.2019.01.038.
[3]
Xie GJ, Huang XY, Li H, et al. Caffeine-related effects on cognitive performance: roles of apoptosis in rat hippocampus following sleep deprivation[J]. Biochem Biophys Res Commun, 2021, 534: 632-638. DOI: 10.1016/j.bbrc.2020.11.029.
[4]
Boutin A, Pinsard B, Boré A, et al. Transient synchronization of hippocampo-striato-thalamo-cortical networks during sleep spindle oscillations induces motor memory consolidation[J]. NeuroImage, 2018, 169: 419-430. DOI: 10.1016/j.neuroimage.2017.12.066.
[5]
谢东东, 程永欣, 田时雨, 等. 原发性失眠患者大脑结构磁共振成像研究[J]. 中国医学物理学杂志, 2020, 37(11): 1380-1383. DOI: 10.3969/j.issn.1005-202X.2020.11.007.
Xie DD, Cheng YX, Tian SY, et al. Structural magnetic resonance imaging of primary insomnia patients & #39; Brian regions[J]. Chin J Med Phys, 2020, 37(11): 1380-1383. DOI: 10.3969/j.issn.1005-202X.2020.11.007.
[6]
Riemann D, Voderholzer U, Spiegelhalder K, et al. Chronic insomnia and MRI-measured hippocampal volumes: a pilot study[J]. Sleep, 2007,30(8): 955-958. DOI: 10.1093/sleep/30.8.955.
[7]
彭博. 原发性失眠患者双侧额叶和海马磁共振波谱成像研究[D]. 广州暨南大学, 2013.
Peng B. A magnetic resonance spectrum imaging study in frontal lobe and Hippocampus of patients with primary insomnia[D]. Guangzhou: Jinan University, 2013.
[8]
高和, 殷光中. 睡眠及其相关事件判读手册[M].北京: 人民卫生出版社, 2018.
Gao H, Yin G Z. Manual for the Scoring of Sleep and Associated Events[M]. Beijing: People's Medical Publishing House, 2018.
[9]
Li C, Ma XF, Dong MS, et al. Abnormal spontaneous regional brain activity in primary insomnia: a resting-state functional magnetic resonance imaging study[J]. Neuropsychiatr Dis Treat, 2016, 12: 1371-1378. DOI: 10.2147/NDT.S109633.
[10]
Endeshaw YW, Yoo W. Association between social and physical activities and insomnia symptoms among community-dwelling older adults[J]. J Aging Health, 2016, 28(6): 1073-1089. DOI: 10.1177/0898264315618921.
[11]
Fortier-Brochu E, Morin CM. Cognitive impairment in individuals with insomnia: clinical significance and correlates[J]. Sleep, 2014, 37(11): 1787-1798. DOI: 10.5665/sleep.4172.
[12]
Li Y, Liu H, Weed JG, et al. Deficits in attention performance are associated with insufficiency of slow-wave sleep in insomnia[J]. Sleep Med, 2016, 24: 124-130. DOI: 10.1016/j.sleep.2016.07.017.
[13]
Benson KL, Bottary R, Schoerning L, et al. 1 H MRS measurement of cortical GABA and glutamate in primary insomnia and major depressive disorder: relationship to sleep quality and depression severity[J]. J Affect Disord, 2020, 274: 624-631. DOI: 10.1016/j.jad.2020.05.026.
[14]
Zhang YC, Zhang ZZ, Wang YL, et al. Dysfunctional beliefs and attitudes about sleep are associated with regional homogeneity of left inferior occidental gyrus in primary insomnia patients: a preliminary resting state functional magnetic resonance imaging study[J]. Sleep Med, 2021, 81: 188-193. DOI: 10.1016/j.sleep.2021.02.039.
[15]
Gong L, Xu RH, Liu D, et al. Abnormal functional connectivity density in patients with major depressive disorder with comorbid insomnia[J]. J Affect Disord, 2020, 266: 417-423. DOI: 10.1016/j.jad.2020.01.088.
[16]
Ji B, Dai M, Guo ZW, et al. Functional connectivity density in the sensorimotor area is associated with sleep latency in patients with primary insomnia[J]. Neuropsychiatr Dis Treat, 2022, 18: 1-10. DOI: 10.2147/ndt.s338489.
[17]
Emamian F, Mahdipour M, Noori K, et al. Alterations of subcortical brain structures in paradoxical and psychophysiological insomnia disorder[J]. Front Psychiatry, 2021, 12: 661286. DOI: 10.3389/fpsyt.2021.661286.
[18]
Morgan PT, Pace-Schott EF, Mason GF, et al. Cortical GABA levels in primary insomnia[J]. Sleep, 2012, 35(6): 807-814. DOI: 10.5665/sleep.1880.
[19]
Plante DT, Jensen JE, Schoerning L, et al. Reduced γ-aminobutyric acid in occipital and anterior cingulate cortices in primary insomnia: a link to major depressive disorder? [J]. Neuropsychopharmacology, 2012, 37(6): 1548-1557. DOI: 10.1038/npp.2012.4.
[20]
Meyerhoff DJ, Mon A, Metzler T, et al. Cortical gamma-aminobutyric acid and glutamate in posttraumatic stress disorder and their relationships to self-reported sleep quality[J]. Sleep, 2014, 37(5): 893-900. DOI: 10.5665/sleep.3654.
[21]
Sarawagi A, Soni ND, Patel AB. Glutamate and GABA homeostasis and neurometabolism in major depressive disorder[J]. Front Psychiatry, 2021, 12: 637863. DOI: 10.3389/fpsyt.2021.637863.
[22]
Ghit A, Assal D, Al-Shami AS, et al. GABA A receptors: structure, function, pharmacology, and related disorders[J]. J Genet Eng Biotechnol, 2021, 19(1): 123. DOI: 10.1186/s43141-021-00224-0.
[23]
Hasegawa H, Selway R, Gnoni V, et al. The subcortical belly of sleep: new possibilities in neuromodulation of basal ganglia? [J]. Sleep Med Rev, 2020, 52: 101317. DOI: 10.1016/j.smrv.2020.101317.
[24]
Javad-Moosavi BZ, Nasehi M, Vaseghi S, et al. Activation and inactivation of nicotinic receptnors in the dorsal hippocampal region restored negative effects of total (TSD) and REM sleep deprivation (RSD) on memory acquisition, locomotor activity and pain perception[J]. Neuroscience, 2020, 433: 200-211. DOI: 10.1016/j.neuroscience.2020.03.006.
[25]
Zarate-Garza PP, Ortega-Balderas JA, de la Barquera JAOS, et al. Hippocampal volume as treatment predictor in antidepressant naïve patients with major depressive disorder[J]. J Psychiatr Res, 2021, 140: 323-328. DOI: 10.1016/j.jpsychires.2021.06.008.
[26]
Yoo D, Lee JY, Kim YK, et al. Mild cognitive impairment and abnormal brain metabolic expression in idiopathic REM sleep behavior disorder[J]. Parkinsonism Relat Disord, 2021, 90: 1-7. DOI: 10.1016/j.parkreldis.2021.07.022.
[27]
Tarun A, Wainstein-Andriano D, Sterpenich V, et al. NREM sleep acid stages specifically alter dynamical integration of large-scale brain networks[J]. iScience, 2020, 24(1): 101923. DOI: 10.1016/j.isci.2020.101923.
[28]
Vasiliadis HM, Lamoureux-Lamarche C, Pitrou I, et al. Sex differences in type of lifetime trauma and suicidal ideation mediated by post-traumatic stress and anxio-depressive disorders in older adults[J]. Int Psychogeriatr, 2020, 32(4): 473-483. DOI: 10.1017/S1041610219001893.

上一篇 慢性高原病脑部多体素1H-MRS研究
下一篇 基于MRI的人与猕猴颞上回听觉区的同源性研究
  
诚聘英才 | 广告合作 | 免责声明 | 版权声明
联系电话:010-67113815
京ICP备19028836号-2