Glutamate Probes in Adolescent Depression

青少年抑郁症的谷氨酸探针

• 批准号: 9208704
• 负责人: Paul E Croarkin
• 金额: $ 16.33万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-02-01 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9208704
• 关键词: Address; Adolescent; Adolescent Psychiatry; Adult; Aftercare; Age; Anterior; Antidepressive Agents; Applications Grants; Award; Basic Science; Benchmarking; Biological Markers; Biology; Brain; Brain imaging; Cerebrospinal Fluid; Chemicals; Child Psychiatry; Childhood; Clinic; Clinical; Clinical Research; Clinical Treatment; Cognition; Comorbidity; Control Groups; Cross-Sectional Studies; Depressed mood; Development; Development Plans; Disease; Ensure; Fluoxetine; Functional disorder; Glutamates; Goals; Grant; Imaging Techniques; International; Knowledge; Longitudinal Studies; Magnetic Resonance Spectroscopy; Major Depressive Disorder; Measures; Mental Depression; Mentored Patient-Oriented Research Career Development Award; Mentors; Methodology; Methods; Neurobiology; Neurosciences; Neurotransmitters; Patient Care; Patients; Pharmaceutical Preparations; Play; Prevalence; Production; Productivity; Protons; Psychotherapy; Public Health; Publications; Recovery; Recurrence; Research; Research Methodology; Research Personnel; Role; Scanning; Schools; Scientist; Selection for Treatments; Selective Serotonin Reuptake Inhibitor; Substance abuse problem; Synapses; Synaptic plasticity; Testing; Training; Transcranial magnetic stimulation; Translational Research; Work; biomarker development; career; career development; child depression; cingulate cortex; disability; experience; improved; in vivo; innovation; mortality; neurochemistry; neurodevelopment; neuroimaging; neurophysiology; neurotransmission; neurotrophic factor; novel; public health relevance; research study; skills; suicidal risk; tool; translational scientist

DESCRIPTION (provided by applicant): This proposal is for a K23 Mentored Patient-Oriented Research Career Development Award to complete training and research experience needed to prepare the candidate for a successful career as an independent investigator. The candidate's long-term goal is a career in academic child and adolescent psychiatry focused on research that improves the care of patients with depression. This will be accomplished through increased understanding of its pathophysiology. Depression is a significant and common illness during childhood, a major public health problem, and a leading causes of disability worldwide. Recent basic science and clinical research in adults with depression suggests that glutamate, the brain's primary excitatory neurotransmitter plays a role in the neurochemical basis of depression. There is little information about the functioning of glutamate in adolescents with depression. Proton magnetic resonance spectroscopy (1H-MRS) is a noninvasive brain imaging technique that measures the concentrations of brain chemicals such as glutamate. Intracortical facilitation (ICF) is a transcranial magnetic stimulation (TMS) neurophysiological test which measures the functioning of glutamate. The candidate proposes to use 1H-MRS and ICF in a cross-sectional study of glutamate concentrations and functioning in adolescent depression [with three groups] of subjects (depressed subjects who have not yet taken an antidepressant medication, subjects who had depression that responded to an antidepressant, and healthy controls). [Depressed subjects will have these two measures repeated after eight weeks of standard clinical treatment with fluoxetine. This will test the hypotheses that cortical glutamate concentrations are decreased while glutamate functioning is increased in adolescents with depression and that successful treatment with fluoxetine normalizes these differences.] This innovative approach will advance understanding of glutamate neurotransmission in adolescent depression, inform the development of new biomarkers, and assist with the identification of treatment targets. This project is tailored to inform subsequent longitudinal studies of depressed adolescents for federal R01 grant applications. The candidate has prior experience with ICF measures but would benefit from additional training in 1H-MRS methodology and TMS neurophysiology paradigms. The candidate and mentoring team propose a career development plan focused on 1H-MRS neuroimaging, TMS neurophysiology studies, clinical and translational research methodologies, [neurodevelopment,] and the neurobiology of disease research. This rigorous plan includes intensive mentoring, courses through the Mayo Clinic Graduate School, and international seminars. Well defined benchmarks regarding publications and grant submissions will ensure substantial productivity during the award period and a successful transition to an independent academic researcher in child and adolescent psychiatry.

描述（由申请人提供）：本提案是K23指导的以患者为导向的研究职业发展奖，以完成培训和研究经验，为候选人作为独立研究者的成功职业生涯做好准备。候选人的长期目标是从事学术儿童和青少年精神病学职业，重点研究改善抑郁症患者的护理。这将通过增加对其病理生理学的理解来实现。抑郁症是儿童时期的一种重要而常见的疾病，是一个重大的公共卫生问题，也是全球残疾的主要原因。最近对成年抑郁症患者的基础科学和临床研究表明，谷氨酸（大脑的主要兴奋性神经递质）在抑郁症的神经化学基础中发挥作用。关于谷氨酸在青少年抑郁症中的作用的信息很少。质子磁共振波谱（1H-MRS）是一种非侵入性脑成像技术，可测量大脑化学物质（如谷氨酸）的浓度。皮质内易化（ICF）是一种经颅磁刺激（TMS）神经生理学测试，用于测量谷氨酸的功能。候选人建议在青少年抑郁症[3组]受试者（尚未服用抗抑郁药的抑郁症受试者、对抗抑郁药有反应的抑郁症受试者和健康对照者）的谷氨酸浓度和功能的横断面研究中使用1H-MRS和ICF。[抑郁受试者将在接受氟西汀标准临床治疗8周后重复这两项测量。这将检验以下假设：青少年抑郁症患者的皮质谷氨酸浓度降低，而谷氨酸功能增加，氟西汀的成功治疗使这些差异正常化。这种创新的方法将促进对青少年抑郁症中谷氨酸神经传递的理解，为新生物标志物的开发提供信息，并有助于确定治疗靶点。这个项目是量身定制的，以告知随后的纵向研究抑郁症青少年的联邦R 01赠款申请。候选人之前有ICF测量经验，但将受益于1H-MRS方法和TMS神经生理学范例的额外培训。候选人和指导团队提出了一个职业发展计划，重点是1H-MRS神经成像，TMS神经生理学研究，临床和转化研究方法，[神经发育，]和疾病研究的神经生物学。这个严格的计划包括密集的指导，通过马约诊所研究生院的课程，和国际研讨会。关于出版物和赠款提交的明确基准将确保在获奖期间的大量生产力，并成功过渡到儿童和青少年精神病学的独立学术研究人员。

项目成果

Paired-Associative Stimulation-Induced Long-term Potentiation-Like Motor Cortex Plasticity in Healthy Adolescents.

• DOI: 10.3389/fpsyt.2017.00095
• 发表时间: 2017
• 期刊: Frontiers in psychiatry
• 影响因子: 4.7
• 作者: Lee JC;Croarkin PE;Ameis SH;Sun Y;Blumberger DM;Rajji TK;Daskalakis ZJ
• 通讯作者: Daskalakis ZJ

Cortical inhibitory and excitatory correlates of depression severity in children and adolescents.

• DOI: 10.1016/j.jad.2015.10.020
• 发表时间: 2016-01-15
• 期刊: Journal of affective disorders
• 影响因子: 6.6
• 作者: Lewis CP;Nakonezny PA;Ameis SH;Vande Voort JL;Husain MM;Emslie GJ;Daskalakis ZJ;Croarkin PE
• 通讯作者: Croarkin PE

How Well Do We Understand the Long-Term Health Implications of Childhood Bullying?

• DOI: 10.1097/hrp.0000000000000137
• 发表时间: 2017-03-01
• 期刊: HARVARD REVIEW OF PSYCHIATRY
• 影响因子: 3.8
• 作者: Patricio Zarate-Garza, Pablo;Biggs, Bridget K.;Tye, Susannah J.
• 通讯作者: Tye, Susannah J.

Transcranial Direct Current Stimulation: Considerations for Research in Adolescent Depression.

经颅直流电刺激：青少年抑郁症研究的考虑因素。

• DOI: 10.3389/fpsyt.2017.00091
• 发表时间: 2017
• 期刊: Frontiers in psychiatry
• 影响因子: 4.7
• 作者: Lee,JonathanC;Lewis,CharlesP;Daskalakis,ZafirisJ;Croarkin,PaulE
• 通讯作者: Croarkin,PaulE

Profile of vortioxetine in the treatment of major depressive disorder: an overview of the primary and secondary literature.

• DOI: 10.2147/tcrm.s55313
• 发表时间: 2015
• 期刊: Therapeutics and clinical risk management
• 影响因子: 2.8
• 作者: Kelliny M;Croarkin PE;Moore KM;Bobo WV
• 通讯作者: Bobo WV