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重大的公共卫生问题，经常在患者的生活中反复出现，对青少年和社会造成重大损失。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。儿童功能性神经影像学研究的数量非常少。少数功能性磁共振成像（fMRI）对儿童抑郁症杏仁核的研究报告了相反的结果。除了首席研究员（杨博士）最近发表的一篇文章外，目前还没有发表的fMRI研究来检查抑郁青少年与匹配的健康青少年的亚掌前扣带或背外侧前额叶皮层。此外，尚无关于抑郁症青少年的功能性神经影像学研究发表，这些研究检查了可能作为未来治疗临床反应预测因素的大脑区域。描述：本研究是一项横断面和纵向随访研究。在本次申请中，我们计划：(1)招募64名重度抑郁症青少年和64名健康对照青少年；(2)对抑郁青少年进行为期6个月的纵向随访。13 - 17岁的重度抑郁症健康青少年将参与本研究。男女和所有种族都将包括在内。招聘将通过几个主要来源，使用与5K23MH070791中建立的相同方法。同样，使用5K23MH070791中建立的相同方法，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。青少年将使用激活青少年杏仁核、背外侧前额皮质和亚膝前扣带皮层的功能磁共振成像任务进行扫描。基线时进行单次功能磁共振成像扫描。临床评估将在基线、3个月和6个月进行。6个月的临床评估将是纵向研究的主要兴趣时间点。儿童抑郁评定量表修订版（CDRS-R）将是主要的临床结果测量。贝克抑郁量表II和儿童整体评估量表将是次要的临床结果测量。目的：目前的建议的目的是：(1)对比MDD青少年和匹配健康对照者的杏仁核、背外侧前额叶皮层（DLPFC）和亚一般前扣带皮层（sgACC）的大脑激活，以及(2)评估杏仁核、DLPFC和sgACC在基线时的fMRI激活与MDD青少年治疗的未来临床反应之间的关系。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研究：(1)促进对青少年抑郁症的全面理解和模型，从而开发临床相关工具；(2)迈出必要的第一步，将基本功能神经影像学发现转化为有用的临床工具，从而预测青少年抑郁症的未来治疗反应。

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.