摘要
目的:
创伤后应激障碍(Posttraumatic stress disorder, PTSD)的脑神经机制还不清楚。研究PTSD患者静息状态下的自发脑功能活动,有助于发现其内在的神经生物学机制和治疗干预目标。本研究使用应用功能磁共振成像(Functional magnetic resonance imaging, fMRI)探查最近发病的PTSD患者静息状态下局部脑功能和功能连接情况。
方法:
在2008年汶川大地震8个月后,我们在两个受灾最严重的区域—德阳市汉旺镇和绵阳市北川县—调查了4200名地震幸存者。德阳市汉旺镇调查了3100名地震幸存者,采用了PTSD筛查清单(PTSD Checklist-Civilian Version, PCL-C)进行PTSD的筛查。对PCL-C总分大于等于35分的受灾者采用精神科医生使用临床用创伤后应激障碍诊断量表(Clinician-Administered PTSD Scale, CAPS)和DSM-IV轴Ⅰ障碍临床定式检查手册(the Structured Clinical Interview for DSM-IV Axis I Disorders, SCID-Ⅰ)进行PTSD的诊断。绵阳市北川县调查了1100名地震幸存者,采用了PCL-C进行PTSD的筛查。对PCL-C总分大于等于45分的受灾者采用CAPS和SCID-Ⅰ进行PTSD的诊断。按照以上的程序诊断出的415名PTSD患者。另外,在PCL-C总分小于30分的被调查者中,应用CAPS和SCID-Ⅰ确定109人为非PTSD作为对照组。以上受试者进一步用SCID-Ⅰ诊断精神科共病。核磁扫描在地震后9月到15个月完成,核磁扫描当天重测SCID和CAPS。最后,有72名PTSD病人和86名年龄、性别匹配的非PTSD对照进行了静息状态fMRI扫描并且其数据进行处理。本研究采用局部一致性(Regional Homogeneity, ReHo)、低频振荡振幅(Amplitude of low-frequency fluctuation, ALFF)和功能连接方法对PTSD静息fMRI数据进行分析。ReHo体现局部脑区神经元活动的同步性,ALFF从能量角度反映了局部脑区各个体素自发神经活动水平的高低,而功能连接是检测不同脑区活动的相关性或解释一个脑区活动和其它脑区活动的关系。应用双样本t检验,分析PTSD和对照组静息状态下ReHo、ALFF和功能连接的差异。
结果:
(1) PTSD患者与创伤对照组相比,左侧顶下小叶和右侧额上回脑区呈现区域一致性信号增强,右侧颞中回和舌回的区域一致性降低(P<0.01,已校正)。在PTSD组中,右侧的额上回和左侧的顶下小叶的ReHo值之间存在正相关(r=0.356,P==0.008)。
(2)与创伤对照组相比,PTSD组静息状态下右侧舌回、楔叶、枕中叶、岛叶和小脑等脑区的ALFF降低,差异有统计学意义(P<0.01,已校正);在右侧额内侧回和额中回脑区的ALFF增高,差异有统计学意义(P<0.01,已校正)。右额内侧回的ALFF值和PTSD症状严重程度呈正相关(r=0.335,P==0.014)。
(3) PTSD组和创伤对照组比较,丘脑-ROI显示正功能连接减少的脑区有:右侧内侧额回和左侧前扣带皮质;与丘脑-ROI的正功能连接增高的脑区包括左侧额中回、双侧额下回、左侧顶下小叶和右侧楔前叶(P<0.05,已校正)。左侧丘脑与右楔前叶的功能连接强度和PTSD症状严重度呈负相关(r=-0.33,P=-0.014)。
结论:
我们的结果表明,地震后短时间内发病的PTSD患者在静息状态下,可能存在固有脑功能活动的异常。
(1)以右侧为主的额叶、颞叶、顶叶和视觉皮质、岛叶和小脑区域等局部功能异常可能与PTSD患者产生创伤记忆和症状的神经机制有关。
(2)丘脑和额叶、顶叶脑区功能连接的异常可能是PTSD记忆改变及过度警觉等症状的病理学基础,并且可能与机体代偿机制相关。
Objective:
Little is known about how brain systems may be altered in posttraumatic stress disorder (PTSD) compared with traumatized individuals not diagnosed with the disorder. The present study investigated the intrinsic brain functional activities using functional magnetic resonance imaging (fMRI) under resting state and identified neurobiological mechanisms of the disorder and targets for intervention.
Methods:
On May12th,2008, an8.0-magnitude earthquake hit Sichuan Province of China, exerting wide and tremendous range of traumatic experience and mental influence on survivors. All subjects for the current study were drawn from a large-scale PTSD survey in those post-earthquake survivors. In brief, investigation was carried out in two most devastated regions8months after the earthquake. A total of3100survivors in Hanwang town were interviewed and screened with the PTSD checklist (PCL). Survivors scoring≥35points were given the Clinician-Administered PTSD Scale (CAPS) and the Structured Clinical Interview for DSM-Ⅳ Axis Ⅰ Disorders (SCID-Ⅰ) by psychiatrists to confirm the PTSD diagnosis. A total of1100survivors in Beichuan county were interviewed and screened with the PCL. Survivors scoring≥45points were given the CAPS and SCID-Ⅰ to confirm the PTSD diagnosis. From these pools of PTSD subjects identified with the above procedure,415with PTSD diagnosis were further selected as eligible for the current functional MRI study. In addition,109non-PTSD controls with PCL total scores below30points and eligibility for MRI were selected as a comparison group. These subjects were further assessed with the SCID-Ⅰ to exclude any psychiatric co-morbidity. At last,72 medication-naive PTSD subjects and86age-, gender-matched traumatized non-PTSD comparison subjects took part in the subsequent resting state fMRI scans. from9months to15months post-earthquake and their data were processed. We analyzed resting fMRI data using regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) as well as functional connectivity measures. ReHo and ALFF are two measures which quantify the function of the brain locally can be implemented in resting-state fMRI studies. ReHo reflects the synchronization of regional neuronal activities and ALFF measures amplitude of spontaneous activity of each pixel in regional sites under resting condition and characterize regional cerebral function, while functional connectivity explores the correlation of activities in different brain regions or explains the relationship of activities between one and the other brain regions. Using two sample t-test, we analyzed the differences of ReHo, ALFF and functional connectivity between the PTSD and comparison groups during the resting state. Results:
(1) PTSD patients presented enhanced regional homogeneity signals in left parietal lobule and right frontal gyrus and reduced ReHo values in right middle temporal gyrus and lingual gyrus relative to traumatized individuals without PTSD (P<0.01, corrected). Significant positive correlations were observed between ReHo values in the left parietal lobule and the right frontal gyrus in the patient group (r=0.356, P=0.008).
(2) PTSD patients showed decreased ALFF values in right lingual gyrus, cuneus, middle occipital gyrus, insula, and cerebellum, and increased ALFF values in right medial and middle frontal gyri, relative to traumatized individuals without PTSD (P<0.01, corrected). The ALFF value in the right medial frontal gyrus was positively correlated with severity of the disorder (r=0.335, P=0.014).
(3) In the PTSD group, the thalamus-ROIs showed decreased positive functional connectivity to particular brain regions including the right medial frontal gyrus and the left anterior cingulate cortex. Importantly, we further found increased positive functional connectivity of thalamus-ROIs with the bilateral inferior frontal and left middle frontal gyrus, as well as left inferior parietal lobule and right precuneus in the PTSD participants when compared with the traumatized controls without PTSD (P<0.05, corrected). The strength of functional connectivity of the left thalamus-ROI to right precuneus showed significant negative correlation with the PTSD symptom severity (r=-0.33, P=0.014).
Conclusion:
Our findings showed that abnormality of intrinsic brain activity exists under resting conditions in recent-onset PTSD exposed to a major earthquake.
(1) Altered regional function found predominantly in right-hemisphere, including frontal lobe, temporal lobe, parietal lobe, visual association cortex, insula and cerebellum areas are likely to contribute to the neural mechanisms underlying traumatic memory and symptoms in PTSD.
(2) Abnormal resting state functional connections linking the thalamus to cortical regions (involving frontal and parietal) may be involved in the underlying pathology to contribute to the altered memory and symptoms such as hyperarousal in PTSD and potential compensatory mechanism.
引文
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