Fronto-limbic Connectivity in Adolescents with MDD

MDD 青少年的额叶边缘连接

基本信息

批准号：
8212487
负责人：
Kathryn Regan Cullen
金额：
$ 16.28万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-03-29 至 2015-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8212487
关键词：
17 year old Address Adolescence Adolescent Anisotropy Anterior Area Biological Neural Networks Biology Brain Childhood Clinical Communities Data Data Set Depressed mood Development Diffusion Diffusion Magnetic Resonance Imaging Early treatment Emotional Foundations Functional Imaging Functional Magnetic Resonance Imaging Functional disorder Future Genetic Handedness Individual Inferior Investigation K-Series Research Career Programs Literature Major Depressive Disorder Matched Group Measures Mediating Mental Depression Methodology Methods Minnesota Neural Pathways Neurobiology Neuronal Plasticity Neurons Pharmaceutical Preparations Pilot Projects Prevalence Process Public Health Recruitment Activity Research Research Infrastructure Research Personnel Rest Sample Size Sampling Scanning Seeds Severities Severity of illness Signal Transduction System Teenagers Time Universities Work aged base cingulate cortex frontal lobe indexing neural circuit neurodevelopment neuroimaging public health relevance relating to nervous system sex therapy development treatment response

项目摘要

DESCRIPTION (provided by applicant): Objective/Hypothesis: Adolescence is a time period notable for significant brain maturation and refinement of neuronal connections, and also for a marked increase in prevalence of Major Depressive Disorder (MDD). Fronto-limbic neural networks mediate emotional processing and are implicated in the pathophysiology of MDD. Our over-arching hypothesis is that MDD results from abnormal development of fronto-limbic neural circuitry. Recent advances in neuroimaging methodology have allowed for measuring the strength of neural connections, or "connectivity". For instance, diffusion tensor imaging (DTI) can be used to measure "structural connectivity", and resting-state functional magnetic resonance imaging (rsfMRI) can be used to measure "functional connectivity". In a preliminary study using these methods in 14 adolescents with MDD and 14 healthy comparison subjects, we identified a reduction in both structural and functional connectivity between the subgenual anterior cingulate cortex and other key fronto-limbic areas in the depressed group. Conclusions from these findings are limited due to confounds related to small sample size and medication exposure in the depressed group. In order to better characterize the developmental abnormalities in fronto-limbic networks in depressed adolescents, we now propose to conduct a multi-modal neuroimaging investigation to examine structural and functional connectivity in a larger, treatment-naive sample. Proposed Methods: 30 adolescents aged 13-17 with familial, adolescent onset, moderate-severe MDD and 30 healthy comparisons matched for sex, handedness, SES and IQ will be recruited from clinical settings at the University of Minnesota and the community. Assessment will include the K-SADS-PL, BDI, CDRS, and WASI. Neuorimaging scans will be obtained at a research-dedicated Siemens 3T scanner at UMN. Structural, diffusion tensor, and resting-state functional images will be collected. Structural connectivity data will be analyzed using a voxel-wise comparison and also using probabilistic tractography. Functional connectivity will be analyzed using a seed-based approach. Discussion/Significance: Demonstration of abnormal connectivity within fronto-limbic neural networks in depressed teens will inform our understanding of the neurodevelopmental mechanisms of adolescent MDD. The dataset from the proposed project will provide the foundation for future longitudinal investigations to (1) delineate trajectories of neural development in individuals with MDD, (2) identify predictors for treatment response, (3) examine the impact of treatment on neural circuitry, and (4) investigate the genetic and environmental underpinnings of abnormal neural development in adolescent MDD. By identifying neurodevelopmental abnormalities that underlie the pediatric depression, our hope is to inform the development of interventions that will alter negative trajectories. PUBLIC HEALTH RELEVANCE: Neurobiological research is urgently needed to address the significant public health burden posed by Major Depressive Disorder (MDD). This illness frequently begins in adolescence. Since early interventions hold promise for impacting malleable systems and altering trajectories, advancement in the neurodevelopmental biology of MDD during adolescence is especially critical.

描述（由申请人提供）：客观/假设：青春期是大脑成熟和神经元联系的重大成熟和完善的时间段，也是重大抑郁症（MDD）明显增加的时间。额叶神经网络介导了情绪处理，并与MDD的病理生理有关。我们的架构假设是MDD是由额 - 边缘神经回路异常发育引起的。神经影像学方法的最新进展允许衡量神经连接或“连通性”的强度。例如，扩散张量成像（DTI）可用于测量“结构连通性”，静止状态功能磁共振成像（RSFMRI）可用于测量“功能连通性”。在14个具有MDD和14个健康比较主题的青少年中使用这些方法的初步研究中，我们确定了抑郁症组中亚果实前扣带回皮层和其他关键额额 - 额叶区域之间的结构和功能连通性的降低。这些发现的结论受到限制，这是由于与抑郁症组中的样本量和药物暴露相关的混杂而受到限制。为了更好地表征抑郁症青少年额 - 边缘网络中的发育异常，我们现在建议进行多模式的神经成像研究，以检查较大的治疗样本中的结构和功能连通性。提出的方法：30名年龄13-17岁的青少年，有家族性，青少年发作，中期MDD和30种与性别，惯用性，SES和智商相匹配的健康比较，将从明尼苏达大学和社区的临床环境中招募。评估将包括K-SADS-PL，BDI，CDR和WASI。将在UMN的研究范围的Siemens 3T扫描仪上获得神经图像扫描。将收集结构，扩散张量和静止状态功能图像。结构连通性数据将使用体素比较分析，并使用概率拖拉术。功能连接将使用基于种子的方法进行分析。讨论/意义：抑郁症青少年额束神经网络中异常连通性的证明将为我们了解我们对青少年MDD神经发育机制的理解。拟议项目的数据集将为（1）MDD患者的神经发育的延伸轨迹为未来的纵向调查提供基础，（2）（2）确定治疗反应的预测因子，（3）检查治疗对神经电路的影响，（4）（4）研究遗传和环境的遗传和环境神经植物的遗传和环境神经性发展的遗传和环境中的神经疗法。通过确定儿科抑郁症构成的神经发育异常，我们的希望是告知会改变负面轨迹的干预措施。公共卫生相关性：迫切需要神经生物学研究来解决主要抑郁症（MDD）造成的重大公共卫生负担。这种疾病经常始于青春期。由于早期干预措施有望影响可延展的系统和改变轨迹，因此在青春期中，MDD神经发育生物学的进步尤其重要。