The Neurobiology of Adolescent Depression

青少年抑郁症的神经生物学

• 批准号: 7346968
• 负责人: Vilma Gabbay
• 金额: $ 18.03万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7346968
• 关键词: 3-Dimensional; Address; Adolescent; Adult; Age; Area; Atrophic; Biometry; Brain; Brain region; Cell Death; Cephalic; Childhood; Choline; Clinical Ethics; Clinical Research; Complement; Consultations; Corpus striatum structure; Data; Development; Diagnostic Specificity; Diagnostics Research; Early identification; Employee Strikes; Ethics; Ethnic Origin; Functional disorder; Gender; Goals; Handedness; Heterogeneity; Image; Invasive; Investigation; Knowledge; Link; Magnetic Resonance Spectroscopy; Major Depressive Disorder; Membrane; Membrane Lipids; Mental Depression; Mentors; Metabolic; Methods; Modeling; Mood Disorders; Morbidity - disease rate; N-acetylaspartate; Neuroanatomy; Neurobiology; Neuroglia; Neuronal Plasticity; Neurons; Neurosciences; Numbers; Pathogenesis; Patient Selection; Personal Satisfaction; Pharmaceutical Preparations; Play; Prefrontal Cortex; Process; Protons; Public Health; Rate; Reporting; Research; Research Methodology; Research Personnel; Resolution; Role; Scanning; Score; Spectrum Analysis; Staging; Techniques; Testing; Training; Week; Youth; affective neuroscience; base; biological research; blood perfusion; career; design; expectation; gray matter; improved; in vivo; magnetic field; mortality; multidisciplinary; neurochemistry; neuroimaging; novel; putamen; resilience; response; tool

DESCRIPTION (provided by applicant): Rationale: Evidence suggests that the pathophysiology of MOD entails alterations of glia and neurons in specific brain regions such as the striatum (i.e., caudate and putamen) and subgenual prefrontal cortex (sgPFC). This application is to initiate an investigation of adolescent MOD through the study of brain neurochemistry using proton magnetic resonance spectroscopy (1H-MRS). 1H-MRS allows the non-invasive in-vivo assessment of intra-cranial metabolite levels such as choline (Cho) and N-acetylaspartate (NAA), which reflect membrane break-down and neuronal viability respectively. Adolescent MOD is associated with serious short and long-term morbidity and mortality. Despite its public health importance, adolescent MOD has been subject to relatively little biological research. Goals: (1) To develop expertise in 1H-MRS through testing for specific neurochemical abnormalities in adolescent MOD. (2) Long-term plans are to become an independent investigator and integrate translational methods into pediatric mood disorder research. Training Plan: Includes training in: (1) MRS and analytic techniques in clinical research, (2) diagnostic and research methods relevant to mood disorders in youth, (3) biostatistics, (4) affective neuroscience, (5) ethics of clinical research, through: (1) didactic courses: MRS, neuroanatomy, biostatistics, neuroscience, and ethics; (2) mentoring; (3) consultation with multidisciplinary experts; (4) participation at scientific meetings; and (5) a research plan that complements career development activities. Research Plan: Specific aim will test hypotheses that adolescents with MOD have significantly lower NAA levels and significantly elevated Cho levels in the caudate and putamen, compared to healthy adolescents. Exploratory aim, will examine NAA and Cho levels in the sgPFC. Methods: Based on power analyses, subjects will consist of a) 30 adolescents, ages 13 through18, with parental MOD (for a relatively homogenous group of adolescent MOD), minimum 8 weeks' duration, CDRS-R scores>40, and onset at >13; b) 30 healthy comparisons without parental MOD, matched to MOD group for gender, age, handedness, and ethnicity; all at Tanner stages 4-5, and psychotropic naive. Neuroimaging will include 3 dimensional multivoxel 1H-MRS acquired at high (3T) magnetic field with high spatial resolution, <1 cm3 voxels focusing on caudate, putamen and sgPFC. Previous spectroscopy has had the limitation of using single voxels with low resolution. Significance: The proposed research will provide knowledge of the neurobiology of MOD during a developmental stage that is particularly vulnerable to neurodevelopmental perturbations. Such knowledge would ultimately improve early identification of MOD, and the development of novel treatments. If findings are promising, larger studies will follow to assess their relevance to MOD in general (familial and non-familial), the prediction of treatment response, and the diagnostic specificity of neurochemical abnormalities.

描述（由申请人提供）：理由：证据表明，MOD的病理生理需要在特定脑部区域（例如纹状体（即尾状和鬼po）和亚蛋白酶前额叶皮层（SGPFC）等特定大脑区域的神经元改变。该应用是通过研究质子磁共振光谱（1H-MR）来研究脑神经化学的研究。 1H-MR允许对颅内代谢产物水平（例如胆碱（CHO）和N-乙酰天冬氨酸）（NAA）进行非侵入性的体内评估，后者分别反映了膜破裂和神经元的生存能力。青春期的模组与严重的短期和长期发病率和死亡率有关。尽管公共健康的重要性，青春期的Mod仍经过相对较少的生物学研究。目标：（1）通过测试青少年MOD中特定的神经化学异常来发展1H-MRS的专业知识。 （2）长期计划将成为独立研究者，并将转化方法整合到小儿情绪障碍研究中。 Training Plan: Includes training in: (1) MRS and analytic techniques in clinical research, (2) diagnostic and research methods relevant to mood disorders in youth, (3) biostatistics, (4) affective neuroscience, (5) ethics of clinical research, through: (1) didactic courses: MRS, neuroanatomy, biostatistics, neuroscience, and ethics; （2）指导； （3）与多学科专家进行咨询； （4）参加科学会议； （5）一个补充职业发展活动的研究计划。研究计划：具体目标将检验假设，与健康的青少年相比，具有MOD的青少年的NAA水平明显降低，并且在尾状和壳质中的CHO水平显着升高。探索目的将检查SGPFC中的NAA和CHO水平。方法：基于功率分析，受试者将包括a）30名青少年，年龄13至18岁，父母MOD（对于相对同质的青少年模式组），至少8周的持续时间为8周，CDRS-R得分> 40，并且在> 13时发作； b）30没有​​父母国防部的健康比较，与Mod组匹配，以适合性别，年龄，惯性和种族；所有这些都在坦纳（Tanner）阶段4-5阶段，而精神幼稚。神经影像学将包括在高空间分辨率的高（3T）磁场上获取的3个维多氧化1H-MR，<1 cm3素体，<1 cm3素，侧重于尾状，pe骨和sgpfc。以前的光谱法具有使用低分辨率的单个体素的局限性。意义：拟议的研究将在一个特别容易受到神经发育扰动的发育阶段提供有关MOD神经生物学的知识。这种知识最终将改善对MOD的早期识别和新型治疗的发展。如果发现很有希望，则将进行更大的研究，以评估它们与MOD（家族性和非家族性），治疗反应的预测以及神经化学异常的诊断特异性的相关性。