矿难所致慢性创伤后应激障碍脑结构和脑功能的研究及随访
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摘要
目的：本课题组曾对矿难后2个月和10个月创伤后应激障碍(Posttraumatic Stress Disorder, PTSD)的流行病学和神经影像学进行了研究。本次研究目的包括以下几个方面：1.调查矿难后2年PTSD的患病率；2.结合弥散张量成像(Diffusion Tensor Imaging, DTI)、三维(Three Dimension,3D)结构磁共振成像以及血氧水平依赖的功能磁共振成像(Blood Oxygen Level-Dependent functional Magnetic Resonance Imaging, BOLD-fMRI)三种不同的技术,探讨矿难后2年慢性创伤后应激障碍患者可能的脑结构和脑功能的病理生理学机制；3.使用DTI技术比较PTSD患者矿难后2年与矿难后10个月脑白质变化；4.使用BOLD-fMRI技术比较PTSD患者慢性期(矿难后2年)与急性期(矿难后2个月)的脑功能的变化。
方法：以矿难后2年的幸存者为研究对象。1.采用诊断和统计手册第四版(Diagnostic and Statistical Manual Version-IV, DSM-IV)轴Ⅰ障碍定式临床检查(Structured Clinical Interview for DSM-IV Axis I Disorders, SCID-I)调查矿难后2年幸存者PTSD的患病率。2.使用创伤后应激障碍清单(PTSD Checklist-Civilian version, PCL-C)、状态-特质焦虑问卷(State-Trait Anxiety Inventory, STAI)、Beck抑郁问卷(Beck depression inventory, BDI)、事件影响量表-修订版(Impact of Event Scale-Revised, IES-R)、临床用PTSD诊断量表(Clinical Administrated PTSD Scale, CAPS)等进行详细评估。3.对矿难后2年符合DSM-IV PTSD诊断标准的20名PTSD受试和14名经过相同矿难但未患PTSD的对照进行韦氏记忆量表-修订版中的逻辑记忆分测验和视觉再生分测验评估,后进行核磁共振检查,包括DTI,3D,BOLD-fMRI(包括症状激发任务和症状激发的短期记忆提取任务)。4.运用MATLAB 6.5和统计参数图(Statistic Parameter Mapping,SPM2)软件对磁共振数据进行处理。
结果：
1.临床研究
(1)PTSD的患病率矿难后2年,原有112名生还者中28名脱落,84名(75%)完成调查。被调查的84名幸存者中,24名符合DSM-IV PTSD的诊断标准,提示矿难后2年PTSD的患病率为28.57%。
(2)症状评估24名PTSD与60名非PTSD在PCL-C回避症状亚分和高警觉症状亚分、IES-R分、BDI分、STAI总分、状态焦虑问卷(State-Trait Anxiety Inventory-state, STAI-s)亚分、特质焦虑问卷(State-Trait Anxiety Inventory-trait, STAI-t)亚分上无明显差异(P>0.05); PTSD患者的PCL-C总分和闯入症状亚分、CAPS总分及其三组亚分均高于非PTSD,其差异具有显著性意义(P<0.05)。
2.脑影像研究
排除头动等导致的数据质量问题,进入统计分析各组样本构成如下：DTI部分：矿难后10个月PTSD患者8名,矿难后2年PTSD患者13名,创伤对照14名；3D部分：矿难后2年PTSD患者12名,创伤对照14名；fMRI部分：矿难后2个月PTSD患者21名,矿难后2年PTSD患者17名,创伤对照14名。结果发现：
(1)DTI①与对照组相比,矿难后2年PTSD组双侧后扣带回、右侧楔前叶、右侧顶叶回下、左侧颞中回白质分数各向异性(Fractional Anisotropy, FA)值明显增加,未发现白质FA值降低的脑区。②矿难后2年PTSD组左侧后扣带回白质FA值与逻辑记忆分呈明显正相关(r=0.61,t=2.55,P=0.027),与PCL-C闯入症状分(r=-0.586,t=-2.398,P=0.035), STAI-t亚分(r=-0.605,t=-2.518,P=0.029)呈明显负相关；右侧后扣带回白质FA值与STAI-s亚分(r=-0.580,t=-2.362,P=0.038), STAI-t亚分呈明显负相关(r=-0.630,t=-2.691,P=0.021)。③与矿难后10个月相比,矿难后2年PTSD组左侧后扣带回白质FA值明显增高,差异有显著性；右侧颞横回、双侧颞叶回下、左侧颞上回、右侧前额叶、右侧额上回、右侧额内侧回、右侧额中回、右侧额叶回下、左侧楔叶白质FA值明显降低,差异有显著性。④矿难后10月PTSD组左侧后扣带回白质FA值与STAI-s亚分呈明显正相关(r=0.773,t=2.986,P=0.024)。
(2)3D与对照组相比,矿难后2年PTSD组左侧豆状核灰质密度增加；右侧颞下回、双侧颞中回、右侧楔前叶、右侧中央前回、右侧顶上小叶、右侧梭状回、左侧后扣带回灰质密度减少。
(3)fMRI①症状激发任务：与对照组相比,矿难后2年PTSD组左侧海马旁回激活增强；右侧楔前叶激活降低。与矿难后2个月相比,矿难后2年PTSD组执行症状激发任务时,未见激活增强的脑区；双侧后扣带回、双侧额中回、左侧顶上小叶、右侧颞中回、右侧楔前叶、右侧梭状回、右侧下丘脑激活降低。②短期记忆提取任务：与对照组比,矿难后2年PTSD组左侧海马旁回、右侧颞上回、左侧中央后回、右侧豆状核的激活降低；未见激活增强的脑区。与矿难后2个月相比,矿难后2年PTSD组在执行短期记忆提取任务时,未发现激活有差异的脑区。
结论：
1.该研究支持后扣带回在情绪调节机制中发挥作用的假说。后扣带回结构和功能异常可能参与PTSD的神经病理学机制,作为PTSD保护机制,来阻止闯入记忆的进一步恶化。随着临床症状的好转,PTSD患者前额叶结构损害减轻,但仍未达到正常水平,前额叶的结构性改变,可能是PTSD情绪和认知功能损害的基础。
2.PTSD在急性期的脑区激活比慢性期要更广泛,其原因可能归结于创伤记忆在PTSD急性期的形成。
3.本研究从神经影像学方面提示颞叶(包括边缘系统)和顶叶、豆状核可能参与了PTSD短时记忆贮存与提取的过程,并可能与PTSD的记忆力下降有关。
Objective:The epidemiological and neuroimaging studies of posttraumatic stress disorder (PTSD) from a coal mining accident after two and ten months were respectively investigated by our research group before. The aim of this study including the following aspects:1. to investigate the prevalence of PTSD 2 years after the coal mining accident; 2. to explore the possible brain functional and structural pathophysiology in chronic PTSD at 2 years post-trauma using diffusion tensor imaging (DTI), three dimension (3D) magnetic resonance imaging and blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI); 3. using DTI to explore brain white matter changes of PTSD between 2 years post-trauma and 10 months post-trauma; 4. using fMRI to find brain functional changes of PTSD between the chronic phase (2 years post-trauma) and the acute phase (2 months post-trauma).
Methods:Subjects were survivors from a coal mine accident which happened 2 years before.1. Structured clinical interview for diagnostic and statistical manual version-Ⅳ(DSM-Ⅳ) axis I disorders (SCID-Ⅰ) was used to evaluate the prevalence of PTSD at 2 years post-trauma.2. The subjects were estimated by PTSD Checklist-Civilian Version (PCL-C), State-trait anxiety inventory (STAI), Beck depression inventory (BDI), Impact of Event Scale-Revised (IES-R), Clinical Administrated PTSD Scale (CAPS).3. Twenty subjects at 2 years post-trauma met the criteria of DSM-IV PTSD and 14 controls from the same trauma but did not develop PTSD were recruited and further estimated by logical memory subtest and visual reproduction subtest of Wechsler Memory Scale-Revised. The PTSD and control groups underwent MRI scan ordering to DTI,3D and BOLD-fMRI (including symptom provocation task and trauma related short-term memory recall task).4. Data were dealt with Matlab 6.5 and Statistic parameter mapping (SPM2) softwares.
Results:
1. Clinical Research
(1) The prevelance of PTSD At 2 years post-trauma,28 miners from the original 112 survivors were off, and 84 miners (75%) complete the survey. Twenty-four miners from the 84 miners met the criteria of DSM-IV PTSD, indicating that the prevalence of PTSD was 28.57%at 2 years post-trauma.
(2) Evaluation of symptoms There were no significant differences in PCL-C avoidance and hyperarousal subscores, IES-R scores, BDI scores, STAI scores, STAI-s and STAI-t subscores (P>0.05) between the 24 PTSD subjects and the 60 non-PTSD subjects. PCL-C scores and intrusion subscores, CAPS scores and three subscores were higher in PTSD than in non-PTSD (P<0.05).
2. Research of brain imaging
Some data were excluded because of head movement. Data could be analyzed finally including 8 PTSD subjects at 10 months post-trauma,13 PTSD subjects as well as 14 controls at 2 years post-trauma in DTI; 12 PTSD subjects and 14 controls at 2 years post-trauma in 3D; 21 PTSD subjects at 2 months post-trauma,17 PTSD subjects and 14 controls at 2 years post-trauma in fMRI. The results were:
(1) DTI①Compared with controls, PTSD at 2 years post-trauma showed significantly higher fractional ahisotropy (FA) in bilateral PCG, right precuneus, right parietal sub-gyrus and left middle temporal gyrus. Regions with lower FA in the PTSD were not found.②FA of left PCG in PTSD at 2 years post-trauma correlated positively with logical memory scores (r=0.61, t=2.55, P=0.027), and negatively with PCL-C intrusion (r=-0.586, t=-2.398, P=0.035) as well as STAI-t subscores (r=-0.605, t=-2.518, P=0.029). FA of right PCG in PTSD at 2 years post-trauma correlated negatively with STAI-s (r=-0.580, t=-2.362, P=0.038) and STAI-t subscores (r=-0.630, t=-2.691, P=0.021).③Compared with 10 months post-trauma, PTSD subjects at 2 years post-trauma showed significantly higher FA in left PCG and lower FA in right transverse temporal gyrus, bilateral temporal sub-gyri, left superior temporal gyrus, right prefrontal gyrus, right superior frontal gyrus, right medial frontal gyrus, right middle frontal gyrus, right frontal sub-gyrus and left cuneus.④FA of left PCG in PTSD at 10 months post-trauma correlated positively with the STAI-s subscores only (r=0.773, R2=0.5978, t=2.986, P=0.024).
(2) 3D Compared with controls, PTSD at 2 years post-trauma showed significantly higher gray matter density in left lenticular nucleus, and significantly lower gray matter density in right inferior temporal gyrus, bilateral middle temporal gyri, right precuneus, right precentral gyrus, right superior parietal gyrus, right fusiform gyrus, left posterior cingulate gyrus.
(3) fMRI①During symptom provocation paradigm, PTSD at 2 years post-trauma showed greater activation in left parahippocampal gyrus and lower activation in right precuneus than controls. PTSD at 2 years post-trauma showed lower activation in bilateral posterior cingulate gyri, bilateral middle frontal gyri, left superior parietal gyrus, right middle temporal gyrus, right precuneus, right fusiform gyrus and right hypothalamus than PTSD at 2 months post-trauma. Regions with higher activation in PTSD at 2 years post-trauma were not found.②During the short-term memory recall paradigm, PTSD at 2 years post-trauma showed lower activation in left parahippocampal gyrus, right superior temporal gyrus, left postcentral gyrus and right lenticular nucleus than controls. Regions with higher activation in PTSD at 2 years post-trauma were not found. There were no regions with significant functional activation in PTSD between 2 months post-trauma and 2 years post-trauma.
Conclusions:
1. These findings support the hypothesis that posterior cingulate gyrus is implicated in affective regulation. The structural and functional abnormalities of posterior cingulate gyrus may take part in the neuropathology of PTSD. It may be a protective strategy for posterior cingulate gyrus to prevent the deterioration of intrusive recollection in PTSD. With the improvement of clinical symptoms, structure deficit of prefrontal gyrus mitigate in PTSD subjects, however, it did not reach the normal level. The structural changes of prefrontal gyrus in PTSD may be the basis of damage of emotion and cognitive function.
2. It suggested that brain activation in the acute phase of PTSD may be more extended than in the chronic phase of PTSD. The reason may due to the formation of traumatic memory in the acute phase of PTSD.
3. The neuroimaging study could show that temporal gyrus (including limbic system), parietal gyrus and lentiform nucleus may be involved in the process of the storage and retrieval in short-term memory, and may be related to memory decline in PTSD.
方法：以矿难后2年的幸存者为研究对象。1.采用诊断和统计手册第四版(Diagnostic and Statistical Manual Version-IV, DSM-IV)轴Ⅰ障碍定式临床检查(Structured Clinical Interview for DSM-IV Axis I Disorders, SCID-I)调查矿难后2年幸存者PTSD的患病率。2.使用创伤后应激障碍清单(PTSD Checklist-Civilian version, PCL-C)、状态-特质焦虑问卷(State-Trait Anxiety Inventory, STAI)、Beck抑郁问卷(Beck depression inventory, BDI)、事件影响量表-修订版(Impact of Event Scale-Revised, IES-R)、临床用PTSD诊断量表(Clinical Administrated PTSD Scale, CAPS)等进行详细评估。3.对矿难后2年符合DSM-IV PTSD诊断标准的20名PTSD受试和14名经过相同矿难但未患PTSD的对照进行韦氏记忆量表-修订版中的逻辑记忆分测验和视觉再生分测验评估,后进行核磁共振检查,包括DTI,3D,BOLD-fMRI(包括症状激发任务和症状激发的短期记忆提取任务)。4.运用MATLAB 6.5和统计参数图(Statistic Parameter Mapping,SPM2)软件对磁共振数据进行处理。
结果：
1.临床研究
(1)PTSD的患病率矿难后2年,原有112名生还者中28名脱落,84名(75%)完成调查。被调查的84名幸存者中,24名符合DSM-IV PTSD的诊断标准,提示矿难后2年PTSD的患病率为28.57%。
(2)症状评估24名PTSD与60名非PTSD在PCL-C回避症状亚分和高警觉症状亚分、IES-R分、BDI分、STAI总分、状态焦虑问卷(State-Trait Anxiety Inventory-state, STAI-s)亚分、特质焦虑问卷(State-Trait Anxiety Inventory-trait, STAI-t)亚分上无明显差异(P>0.05); PTSD患者的PCL-C总分和闯入症状亚分、CAPS总分及其三组亚分均高于非PTSD,其差异具有显著性意义(P<0.05)。
2.脑影像研究
排除头动等导致的数据质量问题,进入统计分析各组样本构成如下：DTI部分：矿难后10个月PTSD患者8名,矿难后2年PTSD患者13名,创伤对照14名；3D部分：矿难后2年PTSD患者12名,创伤对照14名；fMRI部分：矿难后2个月PTSD患者21名,矿难后2年PTSD患者17名,创伤对照14名。结果发现：
(1)DTI①与对照组相比,矿难后2年PTSD组双侧后扣带回、右侧楔前叶、右侧顶叶回下、左侧颞中回白质分数各向异性(Fractional Anisotropy, FA)值明显增加,未发现白质FA值降低的脑区。②矿难后2年PTSD组左侧后扣带回白质FA值与逻辑记忆分呈明显正相关(r=0.61,t=2.55,P=0.027),与PCL-C闯入症状分(r=-0.586,t=-2.398,P=0.035), STAI-t亚分(r=-0.605,t=-2.518,P=0.029)呈明显负相关；右侧后扣带回白质FA值与STAI-s亚分(r=-0.580,t=-2.362,P=0.038), STAI-t亚分呈明显负相关(r=-0.630,t=-2.691,P=0.021)。③与矿难后10个月相比,矿难后2年PTSD组左侧后扣带回白质FA值明显增高,差异有显著性；右侧颞横回、双侧颞叶回下、左侧颞上回、右侧前额叶、右侧额上回、右侧额内侧回、右侧额中回、右侧额叶回下、左侧楔叶白质FA值明显降低,差异有显著性。④矿难后10月PTSD组左侧后扣带回白质FA值与STAI-s亚分呈明显正相关(r=0.773,t=2.986,P=0.024)。
(2)3D与对照组相比,矿难后2年PTSD组左侧豆状核灰质密度增加；右侧颞下回、双侧颞中回、右侧楔前叶、右侧中央前回、右侧顶上小叶、右侧梭状回、左侧后扣带回灰质密度减少。
(3)fMRI①症状激发任务：与对照组相比,矿难后2年PTSD组左侧海马旁回激活增强；右侧楔前叶激活降低。与矿难后2个月相比,矿难后2年PTSD组执行症状激发任务时,未见激活增强的脑区；双侧后扣带回、双侧额中回、左侧顶上小叶、右侧颞中回、右侧楔前叶、右侧梭状回、右侧下丘脑激活降低。②短期记忆提取任务：与对照组比,矿难后2年PTSD组左侧海马旁回、右侧颞上回、左侧中央后回、右侧豆状核的激活降低；未见激活增强的脑区。与矿难后2个月相比,矿难后2年PTSD组在执行短期记忆提取任务时,未发现激活有差异的脑区。
结论：
1.该研究支持后扣带回在情绪调节机制中发挥作用的假说。后扣带回结构和功能异常可能参与PTSD的神经病理学机制,作为PTSD保护机制,来阻止闯入记忆的进一步恶化。随着临床症状的好转,PTSD患者前额叶结构损害减轻,但仍未达到正常水平,前额叶的结构性改变,可能是PTSD情绪和认知功能损害的基础。
2.PTSD在急性期的脑区激活比慢性期要更广泛,其原因可能归结于创伤记忆在PTSD急性期的形成。
3.本研究从神经影像学方面提示颞叶(包括边缘系统)和顶叶、豆状核可能参与了PTSD短时记忆贮存与提取的过程,并可能与PTSD的记忆力下降有关。
Objective:The epidemiological and neuroimaging studies of posttraumatic stress disorder (PTSD) from a coal mining accident after two and ten months were respectively investigated by our research group before. The aim of this study including the following aspects:1. to investigate the prevalence of PTSD 2 years after the coal mining accident; 2. to explore the possible brain functional and structural pathophysiology in chronic PTSD at 2 years post-trauma using diffusion tensor imaging (DTI), three dimension (3D) magnetic resonance imaging and blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI); 3. using DTI to explore brain white matter changes of PTSD between 2 years post-trauma and 10 months post-trauma; 4. using fMRI to find brain functional changes of PTSD between the chronic phase (2 years post-trauma) and the acute phase (2 months post-trauma).
Methods:Subjects were survivors from a coal mine accident which happened 2 years before.1. Structured clinical interview for diagnostic and statistical manual version-Ⅳ(DSM-Ⅳ) axis I disorders (SCID-Ⅰ) was used to evaluate the prevalence of PTSD at 2 years post-trauma.2. The subjects were estimated by PTSD Checklist-Civilian Version (PCL-C), State-trait anxiety inventory (STAI), Beck depression inventory (BDI), Impact of Event Scale-Revised (IES-R), Clinical Administrated PTSD Scale (CAPS).3. Twenty subjects at 2 years post-trauma met the criteria of DSM-IV PTSD and 14 controls from the same trauma but did not develop PTSD were recruited and further estimated by logical memory subtest and visual reproduction subtest of Wechsler Memory Scale-Revised. The PTSD and control groups underwent MRI scan ordering to DTI,3D and BOLD-fMRI (including symptom provocation task and trauma related short-term memory recall task).4. Data were dealt with Matlab 6.5 and Statistic parameter mapping (SPM2) softwares.
Results:
1. Clinical Research
(1) The prevelance of PTSD At 2 years post-trauma,28 miners from the original 112 survivors were off, and 84 miners (75%) complete the survey. Twenty-four miners from the 84 miners met the criteria of DSM-IV PTSD, indicating that the prevalence of PTSD was 28.57%at 2 years post-trauma.
(2) Evaluation of symptoms There were no significant differences in PCL-C avoidance and hyperarousal subscores, IES-R scores, BDI scores, STAI scores, STAI-s and STAI-t subscores (P>0.05) between the 24 PTSD subjects and the 60 non-PTSD subjects. PCL-C scores and intrusion subscores, CAPS scores and three subscores were higher in PTSD than in non-PTSD (P<0.05).
2. Research of brain imaging
Some data were excluded because of head movement. Data could be analyzed finally including 8 PTSD subjects at 10 months post-trauma,13 PTSD subjects as well as 14 controls at 2 years post-trauma in DTI; 12 PTSD subjects and 14 controls at 2 years post-trauma in 3D; 21 PTSD subjects at 2 months post-trauma,17 PTSD subjects and 14 controls at 2 years post-trauma in fMRI. The results were:
(1) DTI①Compared with controls, PTSD at 2 years post-trauma showed significantly higher fractional ahisotropy (FA) in bilateral PCG, right precuneus, right parietal sub-gyrus and left middle temporal gyrus. Regions with lower FA in the PTSD were not found.②FA of left PCG in PTSD at 2 years post-trauma correlated positively with logical memory scores (r=0.61, t=2.55, P=0.027), and negatively with PCL-C intrusion (r=-0.586, t=-2.398, P=0.035) as well as STAI-t subscores (r=-0.605, t=-2.518, P=0.029). FA of right PCG in PTSD at 2 years post-trauma correlated negatively with STAI-s (r=-0.580, t=-2.362, P=0.038) and STAI-t subscores (r=-0.630, t=-2.691, P=0.021).③Compared with 10 months post-trauma, PTSD subjects at 2 years post-trauma showed significantly higher FA in left PCG and lower FA in right transverse temporal gyrus, bilateral temporal sub-gyri, left superior temporal gyrus, right prefrontal gyrus, right superior frontal gyrus, right medial frontal gyrus, right middle frontal gyrus, right frontal sub-gyrus and left cuneus.④FA of left PCG in PTSD at 10 months post-trauma correlated positively with the STAI-s subscores only (r=0.773, R2=0.5978, t=2.986, P=0.024).
(2) 3D Compared with controls, PTSD at 2 years post-trauma showed significantly higher gray matter density in left lenticular nucleus, and significantly lower gray matter density in right inferior temporal gyrus, bilateral middle temporal gyri, right precuneus, right precentral gyrus, right superior parietal gyrus, right fusiform gyrus, left posterior cingulate gyrus.
(3) fMRI①During symptom provocation paradigm, PTSD at 2 years post-trauma showed greater activation in left parahippocampal gyrus and lower activation in right precuneus than controls. PTSD at 2 years post-trauma showed lower activation in bilateral posterior cingulate gyri, bilateral middle frontal gyri, left superior parietal gyrus, right middle temporal gyrus, right precuneus, right fusiform gyrus and right hypothalamus than PTSD at 2 months post-trauma. Regions with higher activation in PTSD at 2 years post-trauma were not found.②During the short-term memory recall paradigm, PTSD at 2 years post-trauma showed lower activation in left parahippocampal gyrus, right superior temporal gyrus, left postcentral gyrus and right lenticular nucleus than controls. Regions with higher activation in PTSD at 2 years post-trauma were not found. There were no regions with significant functional activation in PTSD between 2 months post-trauma and 2 years post-trauma.
Conclusions:
1. These findings support the hypothesis that posterior cingulate gyrus is implicated in affective regulation. The structural and functional abnormalities of posterior cingulate gyrus may take part in the neuropathology of PTSD. It may be a protective strategy for posterior cingulate gyrus to prevent the deterioration of intrusive recollection in PTSD. With the improvement of clinical symptoms, structure deficit of prefrontal gyrus mitigate in PTSD subjects, however, it did not reach the normal level. The structural changes of prefrontal gyrus in PTSD may be the basis of damage of emotion and cognitive function.
2. It suggested that brain activation in the acute phase of PTSD may be more extended than in the chronic phase of PTSD. The reason may due to the formation of traumatic memory in the acute phase of PTSD.
3. The neuroimaging study could show that temporal gyrus (including limbic system), parietal gyrus and lentiform nucleus may be involved in the process of the storage and retrieval in short-term memory, and may be related to memory decline in PTSD.
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