A Cross-Sectional and Longitudinal Functional MRI Study of Adolescent Depression

描述（由申请人提供）：青少年抑郁症是一个主要的公共卫生问题，经常在患者的生活中复发，给青少年和社会带来重大损失。目前，我们对青少年抑郁症的潜在神经基础的理解非常有限。儿科功能性神经影像学研究的数量极其稀少。少数关于儿童抑郁症患者杏仁核的功能性磁共振成像（fMRI）研究报告了相反的结果。除了主要研究者（Yang博士）最近发表的文章外，还没有发表的功能性磁共振成像研究，检查抑郁青少年相对于匹配的健康青少年的膝下前扣带回或背外侧前额叶皮层。此外，还没有发表的功能性神经影像学研究抑郁症青少年检查可能的大脑区域，可能是未来的临床治疗反应的预测。描述：本提案是一项横向和纵向随访研究。在本申请中，我们计划：（1）招募64名患有重度抑郁症（MDD）的青少年和64名健康对照青少年;（2）在初步评估后纵向随访抑郁青少年6个月以上。MDD和13至17岁的健康青少年将参与本研究。将包括所有性别和种族。招募将通过几个主要来源进行，采用与5 K23 MH 070791相同的方法。同样，使用5 K23 MH 070791中确立的相同方法，对所有青少年进行仔细筛选，并进行一系列访谈、问卷调查和评估，以获得与本研究相关的信息。青少年将被扫描使用功能磁共振成像任务，激活青少年杏仁核，背外侧前额叶皮层，和膝下前扣带皮层。将在基线时进行单次fMRI扫描。将在基线、3个月和6个月时进行临床评估。6个月临床评估将是纵向研究的主要关注时间点。儿童抑郁评定量表修订版（CDRS-R）将是主要的临床结局指标。Beck抑郁量表II和儿童总体评估量表将作为次要临床结局指标。目的：本研究的目的是：（1）使用fMRI对比MDD青少年和匹配的健康对照组的杏仁核、背外侧前额叶皮质（DLPFC）和膝下前扣带回皮质（sgACC）的脑激活;（2）评价基线时MDD青少年杏仁核、DLPFC和sgACC的fMRI激活与未来临床治疗反应之间的关系。实现这些目标将推进青少年抑郁症的神经生物学：（1）有助于青少年抑郁症的整体理解和模型，可用于开发临床相关工具，（2）采取必要的第一步，将基本功能神经影像学发现转化为有用的临床工具，可以预测未来抑郁症青少年的治疗反应。 公共卫生相关性：抑郁症是一个主要的公共卫生问题，经常在患者的生活中复发，给青少年和社会带来重大损失。这项功能性磁共振成像研究将通过以下方式促进对青少年抑郁症的理解和治疗：（1）通过对抑郁症和健康青少年进行横断面研究，进一步阐明青少年抑郁症中受影响的皮层和皮层下脑结构的潜在网络，以及（2）采取初步措施，利用从更深入地了解抑郁青少年的大脑结构中获得的知识，帮助发展一种临床相关的功能磁共振成像工具，有可能预测未来的治疗反应，在抑郁症的青少年。

DESCRIPTION (provided by applicant): Adolescent depression is a major public health problem that frequently recurs in the patient's life with significant costs to the adolescent and society. Presently, our understanding of the underlying neural substrates of adolescent depression is very limited. The number of pediatric functional neuroimaging studies is extremely sparse. The few functional magnetic resonance imaging (fMRI) studies of the amygdala in pediatric depression have reported opposite results. There are no published fMRI studies examining the subgenual anterior cingulate or dorsal lateral prefrontal cortex in depressed adolescents relative to matched, healthy adolescents except for the recent publication by the Principal Investigator (Dr. Yang). Furthermore, there are no published functional neuroimaging studies in depressed adolescents examining possible brain regions that might be predictors of future clinical response to treatment. Description: This proposal is both a cross-sectional and longitudinal follow-up study. In this application, we plan to: (1) recruit 64adolescents with major depressive disorder (MDD) and 64 healthy, control adolescents; and (2) follow the depressed adolescents longitudinally over 6 months after the initial assessment. MDD and healthy adolescents ages 13 to 17 years will participate in this study. Both genders and all ethnicities will be included. Recruitment will be through several major sources using the same approach as established in 5K23MH070791. Similarly, using the same approach established in 5K23MH070791, all adolescents will be carefully screened and undergo a series of interviews, questionnaires, and assessments to obtain information pertinent to this study. Adolescents will be scanned using fMRI tasks that activate the adolescent amygdala, dorsal lateral prefrontal cortices, and subgenual anterior cingulate cortex. A single fMRI scan will occur at baseline. Clinical assessments will occur at baseline, 3 months, and 6 months. The 6-month clinical assessment will be the primary time point of interest for the longitudinal study. The Children's Depression Rating Scale-Revised (CDRS-R) will be the primary clinical outcome measure. The Beck Depression Inventory II and Children's Global Assessment Scale will be the secondary clinical outcome measures. Aims: Aims of the current proposal are to: (1) contrast brain activation in the amygdala, dorsal lateral prefrontal cortices (DLPFC), and subgenual anterior cingulate cortex (sgACC) using fMRI between adolescents with MDD and matched healthy controls, and (2) evaluate the relationship between fMRI activation in the amygdala, DLPFC, and sgACC at baseline and the future clinical response to treatment in adolescents with MDD. Accomplishing these aims will advance the neurobiology of adolescent depression by: (1) contributing to an overall understanding and model of adolescent depression that can be used to develop clinically relevant tools, and (2) taking the necessary first steps towards the translation of basic functional neuroimaging findings into a useful clinical tool that can predict future treatment response in depressed adolescents. PUBLIC HEALTH RELEVANCE: Depression is a major public health problem that frequently recurs in the patient's life with significant costs to the adolescent and society. This functional magnetic resonance imaging study will advance the understanding and treatment of adolescent depression by: (1) further elucidating the underlying network of cortical and subcortical brain structures that are affected in adolescent depression by performing a cross- sectional study in depressed and healthy adolescents, and (2) taking the initial steps towards utilizing the knowledge gained from a deeper understanding of which brain structures are affected in depressed adolescents to aid the development of a clinically relevant fMRI tool that has the potential to predict future treatment response in depressed adolescents.