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，在患者的生活中经常复发，给青少年和社会带来了巨大的代价。目前，我们对青少年抑郁症的潜在神经基础的了解非常有限。儿科功能神经影像研究的数量极其稀少。少数对儿童抑郁症患者杏仁核的功能磁共振成像(FMRI)研究报告了相反的结果。除了首席调查员杨博士最近发表的一篇文章外，还没有发表过关于抑郁症青少年亚膝前扣带回或背外侧前额叶皮质相对于匹配的健康青少年的功能磁共振研究。此外，目前还没有发表的关于抑郁症青少年的功能性神经成像研究，这些研究考察了可能预测未来临床治疗反应的大脑区域。描述：这项建议是一项横断面和纵向随访研究。在这项申请中，我们计划：(1)招募64名患有严重抑郁障碍的青少年和健康青少年，作为对照；(2)在最初评估后对抑郁青少年进行6个月以上的纵向跟踪。MDD和13至17岁的健康青少年将参与这项研究。男女和所有种族都将被包括在内。招聘将通过几个主要来源，采用与5K23MH070791中确定的相同方法。同样，使用5K23MH070791中建立的相同方法，将对所有青少年进行仔细筛查，并接受一系列访谈、问卷和评估，以获得与本研究相关的信息。将使用激活青少年杏仁核、背侧前额叶皮质和亚膝前扣带回皮质的fMRI任务对青少年进行扫描。将在基线时进行单次fMRI扫描。临床评估将在基线、3个月和6个月进行。为期6个月的临床评估将是这项纵向研究的主要时间点。修订后的儿童抑郁评定量表(CDRS-R)将是主要的临床结果衡量标准。Beck抑郁量表II和儿童全球评估量表将作为次要的临床结果衡量标准。目的：本研究的目的是：(1)使用功能磁共振成像技术对比MDD青少年和匹配的健康对照青少年之间杏仁核、背外侧前额叶皮质(DLPFC)和扣带回亚皮质(SgACC)的脑激活情况，以及(2)评估基线时杏仁核、DLPFC和sgACC的fMRI激活与MDD青少年患者未来临床疗效的关系。实现这些目标将通过以下方式推进青少年抑郁症的神经生物学：(1)有助于对青少年抑郁症的全面理解和模型，可用于开发临床相关工具；(2)采取必要的第一步，将基本的神经功能成像结果转化为有用的临床工具，可以预测青少年抑郁症的未来治疗反应。 与公共卫生相关：抑郁症是一个主要的公共卫生问题，在患者的生活中经常复发，给青少年和社会带来了巨大的代价。这项功能性磁共振成像研究将通过以下方式推进对青少年抑郁症的理解和治疗：(1)通过对抑郁和健康青少年进行横断面研究，进一步阐明在青少年抑郁症中受影响的皮质和皮质下大脑结构的潜在网络，以及(2)采取初步步骤，利用从更深层次了解哪些大脑结构在抑郁青少年中受到影响而获得的知识，以帮助开发具有临床相关性的功能磁共振工具，该工具有可能预测未来抑郁症青少年的治疗反应。

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.