MRI脑结构、功能成像联合PET脑代谢成像对抑郁症自杀行为的神经影像学研究

项目来源

国家自然科学基金(NSFC)

项目主持人

贾志云

项目受资助机构

四川大学

立项年度

2012

立项时间

未公开

项目编号

81271532

研究期限

未知 / 未知

项目级别

国家级

受资助金额

70.00万元

学科

医学科学-影像医学/核医学-磁共振成像

学科代码

H-H27-H2701

基金类别

面上项目

关键词

磁共振成像 ; 抑郁症 ; 正电子发射计算机成像 ; 自杀 ; 自杀未遂 ; Magnetic resonance imaging ; Positron emission tomography ; Depression ; Suicide ; Suicide attempt

参与者

王昱青;殷莉;吴杞柱;苏鸣岗;杨勋;张华为;张文杰;梁素改;戚忠智

参与机构

重庆大学;浙江大学;国家纳米科学中心;深圳市美德医疗电子技术有限公司

项目标书摘要:抑郁症作为一种常见的情绪障碍性精神疾病,自杀率高,危害较大,带来严重的社会和经济负担。由于发病机制尚不清楚,使得抑郁症自杀的预防比较困难。近年来,神经影像技术的快速发展,为探索抑郁症自杀行为的大脑微结构、功能和代谢改变打开了新的局面,促进了对该病的神经机制的理解。在前期工作中,我们采用弥散张量成像首次对重症抑郁症自杀未遂患者脑白质完整性进行了研究,发现了该类患者特征性的脑白质微结构异常区,提示该病并非完全是功能性精神障碍,而且有其器质性基础。研究成果以第一作者发表在Am J Psychiatry(IF=12.759),得到国际同行的积极评价。在此基础上,本项目拟联合采用磁化传递成像,静息态fMRI功能成像和大脑葡萄糖代谢PET成像,进一步研究抑郁症自杀行为的大脑微结构、静息态功能改变和大脑葡萄糖代谢水平的变化,探索抑郁症自杀行为的神经病理学机制,为抑郁症自杀行为的预防和治疗提供新的思路。

Application Abstract: As a common emotional disorder of mental illness,depression has a much higher suicidal rate which caused great harm and brings about serious social and economic burden.However,the neurobiology of suicide is largely unknown,and the prevention of suicide in depression becomes very difficult in clinic.In recent years,the rapid development of neuroimaging techniques provides new opportunities to characterize the brain microstructural,functional and metabolic changes in depression suicidal patients,and promotes the understanding of its neural mechanism.In previous study,we firstly detected the white matter integrity of suicidal brain in major depressive disorder used diffusion tensor imaging(DTI),and found that these patients have characteristic microstructural abnormalities in brain whiter matter,suggested that this disease was not completely a functional abnormality,but also has organic basis.The result has been published in Am J Psychiatry(Impact factor:12.759)with the applicant Zhiyun Jia as the first author,and get positive evaluation internationally.On the basis of previous study,the project will combined with magnetization transfer imaging(MTI),fMRI resting state functional imaging and brain glucose metabolism imaging with 18F-FDG PET,to further examine the microstructure,resting state functional and brain glucose metabolic changes of suicidal behaviors in depression,which may reveal the potential neurobiological and pathogenesis mechanism underline the suicide in depression,and thus help the prevention and treatment of depressive suicidality.

项目受资助省

四川省

项目结题报告(全文)

抑郁症作为一种常见的情绪障碍性精神疾病,自杀率高,危害较大,带来严重的社会和经济负担。而且由于发病机制尚不清楚,使得抑郁症自杀的预防比较困难。项目通过四年的实施,圆满完成研究任务。我们对重症抑郁症和/或伴自杀未遂病史的脑结构和功能等进行了研究,发现了抑郁症及抑郁症合并自杀后大脑的异常改变,揭示了抑郁症及抑郁症自杀行为发生的潜在机制,为自杀的预防和治疗提供新的方法、思路和指导。项目取得的重要成果包括:(1)对重症抑郁症自杀患者白质神经通路受损的研究,发现Fronto-thalamic纤维通路的异常可能和抑郁症自杀行为相关,为进一步的治疗研究提供了潜在的靶区;(2)对重症抑郁症自杀行为的大脑磁化传递率改变研究,发现该类患者双侧顶叶皮质的异常与注意功能和决策功能降低有关,从而可能增加抑郁症自杀的风险;(3)对首发重症抑郁症患者的磁化传递成像研究,发现首发未用药抑郁症患者在疾病早期顶叶和枕叶灰质的微结构改变,且先于灰质体积降低,这有助于理解抑郁症早期的神经生物学机制;(4)对难治抑郁症患者的磁化传递成像进行研究,发现重症抑郁的药物抵抗机制很有可能是由于脑任务积极网络和默认网络之间的拮抗关系失去平衡所导致。在该基金资助下,项目负责人以第一或通讯作者发表18篇(SCI收录17篇,累计影响因子(IF)>70,IF>3的12篇,其中IF>5的7篇,IF>7的1篇,IF>8的3篇),与本项目相关研究的还有3~4篇待发表。参编《精神影像学》专著1部,获得四川省科技进步一等奖1项,发明专利1项。依托本项目,共联合培养博士后1名,博士研究生3名,硕士研究生3名。在本项目的基础上,项目负责人获得了四川大学优秀青年学者基金,也因此先后晋升硕导(2013年)、博导(2015年)和教授(2016年)。

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  • 1.Brain structure alterations in depression: Psychoradiological evidence

    • 关键词:
    • Psychoradiology; diffusion MRI; magnetic resonance imaging; majordepressive disorder; structure MRI;GRAY-MATTER ALTERATIONS; STATE FUNCTIONAL CONNECTIVITY; 1ST EPISODEDEPRESSION; WHITE-MATTER; CORTICAL THICKNESS; BASAL GANGLIA;ORBITOFRONTAL CORTEX; SUICIDE ATTEMPTERS; MAJOR DEPRESSION; DRUG-NAIVE

    Depression is the leading cause of disability around the world, but little is known about its pathology. Currently, the diagnosis of depression is made based on clinical manifestations, with little objective evidence. Magnetic resonance imaging (MRI) has been used to investigate the pathological changes in brain anatomy associated with this disorder. MRI can identify structural alterations in depressive patients in vivo, which could make considerable contributions to clinical diagnosis and treatment. Numerous studies that focused on gray and white matter have found significant brain region alterations in major depressive disorder patients, such as in the frontal lobe, hippocampus, temporal lobe, thalamus, striatum, and amygdala. The results are inconsistent and controversial because of the different demographic and clinical characteristics. However, some regions overlapped; thus, we think that there may be a "hub" in MDD and that an impairment in these regions contributes to disease severity. Brain connections contain both structural connections and functional connections, which reflect disease from a different view and support that MDD may be caused by the interaction of multiple brain regions. According to previous reports, significant circuits include the frontal-subcortical circuit, the suicide circuit, and the reward circuit. As has been recognized, the pathophysiology of major depressive disorder is complex and changeable. The current review focuses on the significant alterations in the gray and white matter of patients with the depressive disorder to generate a better understanding of the circuits. Moreover, identifying the nuances of depressive disorder and finding a biomarker will make a significant contribution to the guidance of clinical diagnosis and treatment.

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  • 2.Brain structure alterations in depression: Psychoradiological evidence

    • 关键词:
    • Psychoradiology; diffusion MRI; magnetic resonance imaging; majordepressive disorder; structure MRI;GRAY-MATTER ALTERATIONS; STATE FUNCTIONAL CONNECTIVITY; 1ST EPISODEDEPRESSION; WHITE-MATTER; CORTICAL THICKNESS; BASAL GANGLIA;ORBITOFRONTAL CORTEX; SUICIDE ATTEMPTERS; MAJOR DEPRESSION; DRUG-NAIVE

    Depression is the leading cause of disability around the world, but little is known about its pathology. Currently, the diagnosis of depression is made based on clinical manifestations, with little objective evidence. Magnetic resonance imaging (MRI) has been used to investigate the pathological changes in brain anatomy associated with this disorder. MRI can identify structural alterations in depressive patients in vivo, which could make considerable contributions to clinical diagnosis and treatment. Numerous studies that focused on gray and white matter have found significant brain region alterations in major depressive disorder patients, such as in the frontal lobe, hippocampus, temporal lobe, thalamus, striatum, and amygdala. The results are inconsistent and controversial because of the different demographic and clinical characteristics. However, some regions overlapped; thus, we think that there may be a "hub" in MDD and that an impairment in these regions contributes to disease severity. Brain connections contain both structural connections and functional connections, which reflect disease from a different view and support that MDD may be caused by the interaction of multiple brain regions. According to previous reports, significant circuits include the frontal-subcortical circuit, the suicide circuit, and the reward circuit. As has been recognized, the pathophysiology of major depressive disorder is complex and changeable. The current review focuses on the significant alterations in the gray and white matter of patients with the depressive disorder to generate a better understanding of the circuits. Moreover, identifying the nuances of depressive disorder and finding a biomarker will make a significant contribution to the guidance of clinical diagnosis and treatment.

    ...
  • 3.Brain gray matter alterations and associated demographic profiles in adults with autism spectrum disorder: A meta-analysis of voxel-based morphometry studies

    • 关键词:
    • Autism spectrum disorder; adult; voxel-based morphometry; meta-analysis;HIGH-FUNCTIONING AUTISM; SUPERIOR TEMPORAL SULCUS; WHITE-MATTER;CORTICAL THICKNESS; REPETITIVE BEHAVIOR; COGNITIVE CONTROL; CHILDHOODAUTISM; SEX-DIFFERENCES; CHILDREN; ABNORMALITIES

    Background: There is increasing evidence that children with autism spectrum disorder are accompanied by specific anatomical alterations. However, the anatomical abnormalities in adults with autism spectrum disorder are poorly understood. This study was aimed to identify the neuroanatomical substrates underlying the pathophysiology of adults with autism spectrum disorder. We also investigated the relationship between neuroanatomical alterations and clinical and demographic characteristics.Methods: A total of 13 datasets were enrolled, of which 12 studies compared whole-brain differences of 382 adult patients with autism and 393 healthy control subjects. We conducted a meta-analysis to quantitatively estimate regional gray matter volume abnormalities in individuals with autism using the effect-size signed differential mapping.Results: The voxel-wise meta-analysis revealed that relative to controls, adults with autism spectrum disorder had significantly increased gray matter volume in the middle temporal gyrus, superior temporal gyrus, postcentral gyrus and parahippocampal gyrus, and reduced gray matter volume in the anterior cingulate cortex and cerebellum. Variations in gray matter volume were significantly associated with the mean age and mean total IQ score of the patients, as well as with the percentage of male patients with autism.Conclusion: These findings confirmed that the neuroanatomical alterations in the fronto-temporal cortices, limbic system and cerebellum in adult individuals with autism were different from the children and young adolescent's autism. The effects of demographic characteristics on the brain morphological changes allow us to further clarify the neurobiological mechanisms and developmental trajectory in adult population with autism spectrum disorder.

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  • 4.Performance of PET/CT for Detecting the Primary Tumors of Cervical Metastases from Unknown Primary Carcinoma: A Systematic Review and Meta-Analysis

    • 关键词:
    • 18F-FDG PET/CT; cervical metastasis; diagnostic value; meta-analysis;unknown primary carcinoma;POSITRON-EMISSION-TOMOGRAPHY; LYMPH-NODE METASTASES; OCCULT PRIMARYHEAD; SQUAMOUS-CELL-CARCINOMA; FDG-PET; NECK CANCERS; F-18-FDG PET;MANAGEMENT; IMPACT; LYMPHADENOPATHY

    In recent years, fluorine 18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) has emerged as a new modality for detecting the primary site of cervical metastases from unknown primary carcinoma (UPC). The aim of this meta-analysis was to assess the diagnostic value of 18F-FDG PET/CT in detecting primary tumors in UPC patients with cervical metastases. After systematic search for eligible studies and data extraction, we determined pooled sensitivities and specificities across studies, calculated positive and negative likelihood ratios, and constructed summary receiver operating characteristic curves with area under the curve (AUC) and Q* obtained. We also analyzed the heterogeneity between studies based on subgroup-analysis and publication bias. Totally, 39 studies involving 1468 patients met the inclusion criteria. The pooled sensitivity and specificity were 0.90 (95% confidence interval [CI], 0.87-0.92) and 0.79 (95% CI, 0.75-0.81), respectively. Likelihood ratio syntheses yielded overall PLR of 3.50 (95% CI, 3.00-4.08) and NLR of 0.20 (95% CI, 0.15-0.26). The AUC and Q* index were 0.8930 and 0.8238, respectively. The heterogeneity was only significantly observed in sensitivity. PET/CT is beneficial in the overall assessment of primary tumors in UPC patients with cervical metastases. Large, multicenter, and prospective studies with standard protocols are now needed to investigate the true value of PET/CT for detecting primary tumors of cervical metastases from UPC and the broad application of this method in clinical practice.

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  • 5.Brain gray matter alterations in first episodes of depression: A meta-analysis of whole-brain studies

    • 关键词:
    • Meta-analysis; First episode depression; Voxel-based morphometry (VBM);Effect-size signed differential mapping (ES-SDM);CEREBRAL-BLOOD-FLOW; VOLUME ABNORMALITIES; AMYGDALA VOLUMES; MAJORDEPRESSION; DRUG-NAIVE; DISORDER; 1ST-EPISODE; HIPPOCAMPAL; ACTIVATION;REDUCTION

    Though numerous studies have implicated structural abnormalities in chronically depressive patients, relatively little attention has been paid to the brain alterations in patients experiencing first episode depression (FED). The investigation of FED is important for elucidating the core pathophysiology of this disease independent of other potentially confounding factors. The present study was to provide a quantitative voxelwise meta-analysis of gray matter (GM) changes in FED using effect-size signed differential mapping (ES-SDM). The pooled meta-analysis revealed GM reductions in the right supplementary motor area, left insula, and right middle temporal gyrus in FED patients compared with the healthy controls. No GM volume increases were found. The meta-regression analyses showed that studies including patients with higher HDRS scores were significantly more likely to present reduced GM volumes in the right amygdala. This meta-analysis indicates that FED patients have significantly and robustly reduced gray matter mainly associated with emotion regulation and sensorimotor areas alterations may be specific changes in early stage of this disease. (C) 2015 Elsevier Ltd. All rights reserved.

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  • 6.Cortical and subcortical gray matter shrinkage in alcohol-use disorders: a voxel-based meta-analysis

    • 关键词:
    • Meta-analysis; Alcohol-use disorder (AUD); Gray matter volume;Voxel-based morphometry (VBM);ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; STATE FUNCTIONAL CONNECTIVITY;NATIONAL EPIDEMIOLOGIC SURVEY; CUE-INDUCED ACTIVATION; RESTING-STATE;PREFRONTAL CORTEX; HIPPOCAMPAL VOLUME; SUBSEQUENT RELAPSE; BRAINMORPHOMETRY; NEUROIMAGING DATA

    Although gray matter (GM) damages caused by long term and excessive alcohol consumption have long been reported, the structural neuroimaging findings on alcohol-use disorders (AUD) are inconsistent. The aim of this study was to conduct a meta-analysis, using a novel voxel-based meta-analytic method effect size signed differential mapping (ES-SDM), to characterize GM changes in AUD patients. Twelve studies including 433 AUD patients and 498 healthy controls (HCs) were retrieved. The AUD group demonstrated significant GM reductions in the corticostriatal-limbic circuits, including bilateral insula, superior temporal gyrus, striatum, dorsal lateral prefrontal cortex (DLPFC), precentral gyrus, anterior cingulate cortex (ACC), left thalamus and right hippocampus compared to HCs. GM reduction in the right striatum is significantly negatively related to duration of alcohol dependence, while GM shrinkage of the left superior, middle frontal gyrus, and left thalamus is related to lifetime alcohol consumption. The findings demonstrate that the GM abnormalities caused by AUD are in corticostriatal-limbic circuits whose dysfunctions may involve in craving and observed functional deficits. (C) 2016 Elsevier Ltd. All rights reserved.

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  • 7.Cortical and subcortical gray matter shrinkage in alcohol-use disorders: a voxel-based meta-analysis

    • 关键词:
    • Meta-analysis; Alcohol-use disorder (AUD); Gray matter volume;Voxel-based morphometry (VBM);ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; STATE FUNCTIONAL CONNECTIVITY;NATIONAL EPIDEMIOLOGIC SURVEY; CUE-INDUCED ACTIVATION; RESTING-STATE;PREFRONTAL CORTEX; HIPPOCAMPAL VOLUME; SUBSEQUENT RELAPSE; BRAINMORPHOMETRY; NEUROIMAGING DATA

    Although gray matter (GM) damages caused by long term and excessive alcohol consumption have long been reported, the structural neuroimaging findings on alcohol-use disorders (AUD) are inconsistent. The aim of this study was to conduct a meta-analysis, using a novel voxel-based meta-analytic method effect size signed differential mapping (ES-SDM), to characterize GM changes in AUD patients. Twelve studies including 433 AUD patients and 498 healthy controls (HCs) were retrieved. The AUD group demonstrated significant GM reductions in the corticostriatal-limbic circuits, including bilateral insula, superior temporal gyrus, striatum, dorsal lateral prefrontal cortex (DLPFC), precentral gyrus, anterior cingulate cortex (ACC), left thalamus and right hippocampus compared to HCs. GM reduction in the right striatum is significantly negatively related to duration of alcohol dependence, while GM shrinkage of the left superior, middle frontal gyrus, and left thalamus is related to lifetime alcohol consumption. The findings demonstrate that the GM abnormalities caused by AUD are in corticostriatal-limbic circuits whose dysfunctions may involve in craving and observed functional deficits. (C) 2016 Elsevier Ltd. All rights reserved.

    ...
  • 8.Brain gray matter alterations and associated demographic profiles in adults with autism spectrum disorder: A meta-analysis of voxel-based morphometry studies

    • 关键词:
    • Autism spectrum disorder; adult; voxel-based morphometry; meta-analysis;HIGH-FUNCTIONING AUTISM; SUPERIOR TEMPORAL SULCUS; WHITE-MATTER;CORTICAL THICKNESS; REPETITIVE BEHAVIOR; COGNITIVE CONTROL; CHILDHOODAUTISM; SEX-DIFFERENCES; CHILDREN; ABNORMALITIES

    Background: There is increasing evidence that children with autism spectrum disorder are accompanied by specific anatomical alterations. However, the anatomical abnormalities in adults with autism spectrum disorder are poorly understood. This study was aimed to identify the neuroanatomical substrates underlying the pathophysiology of adults with autism spectrum disorder. We also investigated the relationship between neuroanatomical alterations and clinical and demographic characteristics.Methods: A total of 13 datasets were enrolled, of which 12 studies compared whole-brain differences of 382 adult patients with autism and 393 healthy control subjects. We conducted a meta-analysis to quantitatively estimate regional gray matter volume abnormalities in individuals with autism using the effect-size signed differential mapping.Results: The voxel-wise meta-analysis revealed that relative to controls, adults with autism spectrum disorder had significantly increased gray matter volume in the middle temporal gyrus, superior temporal gyrus, postcentral gyrus and parahippocampal gyrus, and reduced gray matter volume in the anterior cingulate cortex and cerebellum. Variations in gray matter volume were significantly associated with the mean age and mean total IQ score of the patients, as well as with the percentage of male patients with autism.Conclusion: These findings confirmed that the neuroanatomical alterations in the fronto-temporal cortices, limbic system and cerebellum in adult individuals with autism were different from the children and young adolescent's autism. The effects of demographic characteristics on the brain morphological changes allow us to further clarify the neurobiological mechanisms and developmental trajectory in adult population with autism spectrum disorder.

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  • 9.Diagnostic performance of diffusion-weighted MRI for detection of pelvic metastatic lymph nodes in patients with cervical cancer: a systematic review and meta-analysis

    • 关键词:
    • GYNECOLOGIC-ONCOLOGY-GROUP; PROGNOSTIC VARIABLES; STAGE-IB; CARCINOMA;ENDOMETRIAL; DIFFERENTIATION; ARTIFACTS; INDICATOR; THERAPY

    In recent years, diffusion-weighted (DW) MRI has emerged as a new technique for detecting the pelvic lymph metastases in patients with cervical cancer. The aim of this meta-analysis was to assess the diagnostic value of DW imaging (DWI) for benign/malignant discrimination of pelvic lymph nodes (LNs). Studies about DWI for the detection of metastatic LNs were searched in the PubMed, EMBASE, Web of Science, EBSCO, the Cochrane Library and three Chinese databases. Based on the extracted data, we determined pooled sensitivities, specificities and diagnostic odds ratios (DORs) across studies, calculated positive and negative likelihood ratios (LRs) and constructed summary receiver operating characteristic curves with area under the curve (AUC) and Q* obtained. We also analysed the heterogeneity between studies based on subgroup analysis, threshold effect and publication bias. In total, 15 studies involving 1021 patients met the inclusion criteria. The pooled sensitivity, specificity and DOR of DWI were 0.86 [95% confidence interval (CI), 0.84-0.89], 0.84 (95% CI, 0.83-0.86) and 47.21 (95% CI, 25.67-86.81), respectively. LR syntheses yielded overall positive LR of 6.55 (95% CI, 4.77-9.01) and negative LR of 0.17 (95% CI, 0.12-0.23). The AUC and Q* index were 0.9384 and 0.8754, respectively. The heterogeneity was relatively high between studies; however, there was no evidence for threshold effect and publication bias. DWI is beneficial in the pelvic nodal assessment in patients with cervical cancer. Large-scale, high-quality trials with standard protocols are required to evaluate its clinical value for discrimination of metastatic from non-metastatic pelvic LNs in patients with cervical cancer. Advances in knowledge include providing evidence to assess the role of DWI in nodal staging of cervical cancer.

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  • 10.Comparison of choline-PET/CT, MRI, SPECT, and bone scintigraphy in the diagnosis of bone metastases in patients with prostate cancer: a meta-analysis

    • 关键词:
    • Bone metastases; Prostate cancer; Positron emission tomography withcomputed tomography; MRI; Bone scintigraphy; SPECT; Meta-analysis;POSITRON-EMISSION-TOMOGRAPHY; FIELD-OF-VIEW; AXIAL SKELETON; VERTEBRALMETASTASES; FDG-PET; CT; SCAN; FLUOROCHOLINE; DISEASE; RELAPSE

    Published data on the diagnosis of bone metastases of prostate cancer are conflicting and heterogeneous. We performed a comprehensive meta-analysis to compare the diagnostic performance of choline-PET/CT, MRI, bone SPECT, and bone scintigraphy (BS) in detecting bone metastases in parents with prostate cancer. Pooled sensitivity, specificity, and diagnostic odds ratios (DOR) were calculated both on a per-patient basis and on a per-lesion basis. Summary receiver operating characteristic (SROC) curves were also drawn to obtain the area under curve (AUC) and Q* value. Sixteen articles consisting of 27 studies were included in the analysis. On a per-patient basis, the pooled sensitivities by using choline PET/CT, MRI, and BS were 0.91 [95 % confidence interval (CI): 0.83-0.96], 0.97 (95 % CI: 0.91-0.99), 0.79 (95 % CI: 0.73-0.83), respectively. The pooled specificities for detection of bone metastases using choline PET/CT, MRI, and BS, were 0.99 (95 % CI: 0.93-1.00), 0.95 (95 % CI: 0.90-0.97), and 0.82 (95 % CI: 0.78-0.85), respectively. On a per-lesion basis, the pooled sensitivities of choline PET/CT, bone SPECT, and BS were 0.84 (95 % CI: 0.81-0.87), 0.90 (95 % CI: 0.86-0.93), 0.59 (95 % CI: 0.55-0.63), respectively. The pooled specificities were 0.93 (95 % CI: 0.89-0.96) for choline PET/CT, 0.85 (95 % CI: 0.80-0.90) for bone SPECT, and 0.75 (95 % CI: 0.71-0.79) for BS. This meta-analysis indicated that MRI was better than choline PET/CT and BS on a per-patient basis. On a per-lesion analysis, choline PET/CT with the highest DOR and Q* was better than bone SPECT and BS for detecting bone metastases from prostate cancer.

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