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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：
8606509
负责人：
Kathryn Regan Cullen
金额：
$ 16.19万
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 2016-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8606509
关键词：
17 year old Address Adolescence Adolescent Anisotropy Anterior Area Biological Neural Networks Biology Brain Clinical Communities Data Data Set Depressed mood Development Diffusion Diffusion Magnetic Resonance Imaging Early Intervention 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 child depression 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）：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、青少年发病、中重度MDD的13-17岁青少年和30名性别、利手、SES和智商匹配的健康对照。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。公共卫生关系：神经生物学研究是迫切需要解决重大的公共卫生负担所造成的严重抑郁症（MDD）。这种疾病通常始于青春期。由于早期干预有望影响可塑性系统和改变轨迹，因此在青春期MDD的神经发育生物学方面取得进展尤为重要。

项目成果

期刊论文数量（13）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Executive Attention Impairment in Adolescents With Major Depressive Disorder.

DOI：
10.1080/15374416.2015.1072823
发表时间：
2016
期刊：
Journal of clinical child and adolescent psychology : the official journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53
影响因子：
0
作者：
Sommerfeldt SL;Cullen KR;Han G;Fryza BJ;Houri AK;Klimes-Dougan B
通讯作者：
Klimes-Dougan B

Classification of borderline personality disorder based on spectral power of resting-state fMRI.

DOI：
10.1109/embc.2014.6944756
发表时间：
2014
期刊：
Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference
影响因子：
0
作者：
Xu T;Cullen KR;Houri A;Lim KO;Schulz SC;Parhi KK
通讯作者：
Parhi KK

Increases in orbitofrontal cortex thickness following antidepressant treatment are associated with changes in resting state autonomic function in adolescents with major depression - Preliminary findings from a pilot study.

DOI：
10.1016/j.pscychresns.2018.08.013
发表时间：
2018-11-30
期刊：
Psychiatry research. Neuroimaging
影响因子：
0
作者：
Koenig J;Westlund Schreiner M;Klimes-Dougan B;Ubani B;Mueller BA;Lim KO;Kaess M;Cullen KR
通讯作者：
Cullen KR

Coordination between frontolimbic resting state connectivity and hypothalamic-pituitary-adrenal axis functioning in adolescents with and without depression.