Fronto-limbic Connectivity in Adolescents with MDD

描述（由申请人提供）：目的/假设：青春期是一个显著的大脑成熟和神经元连接细化的时期，也是重度抑郁症（MDD）患病率显著增加的时期。额叶边缘神经网络介导情绪处理，并与MDD的病理生理学有关。我们的过度假设是，MDD的结果异常发展的额边缘神经回路。神经影像学方法的最新进展已经允许测量神经连接或“连接性”的强度。例如，扩散张量成像（DTI）可用于测量“结构连接”，静息态功能磁共振成像（rsfMRI）可用于测量“功能连接”。在一项初步研究中，使用这些方法在14名青少年与抑郁症和14名健康的对照科目，我们确定了减少的结构和功能之间的连接膝下前扣带皮层和其他关键的额边缘区在抑郁症组。这些发现的结论是有限的，由于混淆相关的小样本量和药物暴露在抑郁症组。为了更好地描述抑郁症青少年额叶边缘系统网络的发育异常，我们现在建议进行多模态神经影像学研究，以检查结构和功能的连接，在一个更大的，未经治疗的样本。建议的方法：将从明尼苏达大学和社区的临床环境中招募30名患有家族性、青少年发作、中重度MDD的13-17岁青少年和30名性别、利手、SES和IQ匹配的健康对照。评估将包括K-SADS-PL、BDI、CDRS和WASI。将在UMN的研究专用Siemens 3 T扫描仪上进行神经成像扫描。将收集结构、弥散张量和静息状态功能图像。将使用体素比较和概率纤维束成像分析结构连通性数据。将使用基于种子的方法分析功能连接。讨论/意义：抑郁青少年额叶边缘神经网络异常连接的证明将为我们了解青少年MDD的神经发育机制提供信息。来自拟议项目的数据集将为未来的纵向研究提供基础，以（1）描绘MDD患者神经发育的轨迹，（2）确定治疗反应的预测因素，（3）检查治疗对神经回路的影响，以及（4）调查青少年MDD异常神经发育的遗传和环境基础。通过识别儿童抑郁症的神经发育异常，我们希望能够为改变消极轨迹的干预措施的发展提供信息。

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.