Stress and MDD effects on mPFC Glutamate and GABA during reward processing

奖励处理过程中压力和 MDD 对 mPFC 谷氨酸和 GABA 的影响

基本信息

批准号：
9212197
负责人：
Michael Tilghman Treadway
金额：
$ 24.23万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-02-09 至 2018-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9212197
关键词：
Acute Address Affective Age Amino Acids Anhedonia Animal Model Behavior Behavior assessment Behavioral Model Behavioral inhibition Biological Psychiatry Cause of Death Corpus striatum structure Data Decision Making Depressed mood Development Environment Equilibrium Evaluation Functional Magnetic Resonance Imaging Functional disorder Gender Glutamates Goals Hormonal Human Hydrocortisone Impairment Individual Individual Differences Laboratories Learning Link Literature Magnetic Resonance Spectroscopy Major Depressive Disorder Measures Medial Mediating Mediator of activation protein Mental disorders Mentors Modeling Mood Disorders Motivation Multimodal Imaging Neurotic Disorders Neurotics Neurotransmitters Operant Conditioning Participant Patient Self-Report Patients Performance Phase Prefrontal Cortex Preparation Prevalence Process Protons Psychological reinforcement Psychosocial Stress Punishment Reading Research Rest Rewards Risk Factors Role Salivary Sampling Scanning Schools Signal Transduction Stress Supervision Symptoms Technical Expertise Techniques Testing Training United States Work acute stress behavior measurement cognitive neuroscience depressive symptoms design disability gamma-Aminobutyric Acid imaging study in vivo information processing insight learned behavior meetings neuroimaging neurotransmission psychosocial response reward processing skills social social stress stress reactivity stressor symptomatology trait

项目摘要

Project Summary With a lifetime prevalence of 16%, Major Depressive Disorder (MDD) is predicted to become the second leading cause of death and disability in the United States by the year 2020. A core feature of MDD is reward- processing deficits in the form of decreased reward motivation and anhedonia. These deficits have been linked to alterations in corticostriatal networks in MDD, but less is known about the specific mechanisms that may contribute to these changes. One candidate mechanism is alterations in medial prefrontal glutamate (Glu) and GABA, both of which have recently been implicated in both MDD, as well as a key risk-factor for the development of MDD, stress. To date however, no study has provided an in vivo assessment of Glu and GABA function in response to psychosocial stress in MDD or in healthy controls. To address this question, the K99 phase of this application proposes the following training goals. First, in order to develop the technical skills needed to assess Glu and GABA in vivo, the candidate will learn MR-Spectroscopy techniques from Dr. J. Eric Jensen (K99 Co-mentor) and Dr. Dost Ongür (Consultant). This will involve the completion of a combined MRS/fMRI study that will explore the relationships between baseline Glu and GABA function and BOLD fMRI signals during reinforcement learning in healthy participants. Second, the candidate will deepen his understanding of the role of Glu and GABA function in reward processing through directed readings with Dr. Kent Berridge (Consultant) as well as their relevance to the pathophysiology of mood disorders through readings supervised by Dr. Ongür. Third, he will build upon his behavioral modeling skills developed in graduate school through the application of a reinforcement learning paradigm and associated Q-learning model analysis, which will be supervised by Dr. Michael Frank (Consultant); the candidate will also attend Dr. Frank’s lab meetings on a monthly basis as well as his course “Computational Cognitive Neuroscience”. Finally, the candidate will receive guidance and supervision from his primary mentor, Dr. Diego Pizzagalli, in the integration multimodal imaging data, design and analysis of laboratory stressors, and preparation towards the development of an independent laboratory. During the independent phase, two additional multimodal imaging studies are proposed that will combine MRS assessment of Glu and GABA function with fMRI measures of reinforcement learning both before and after a psycho-social stressor. The first of these studies will be focused on healthy controls, while the second will include a sample of patients with MDD and matched controls. Through its use of multimodal imaging focused on two major neurotransmitters, a pre-post stress manipulation and inclusion of both controls and MDD patients, the proposed research will provide important new insights into the role of Glu and GABA function in the pathophysiology of reward processing deficits in MDD.

项目摘要终身患病率为16％，预计重度抑郁症（MDD）成为第二个到2020年，美国的主要死亡和残疾原因。MDD的核心特征是奖励 - 处理以减少的奖励动机和抗议的形式定义。这些定义已经与MDD中皮质纹状体网络的变化有关，但对特定机制的了解却鲜为人知可能会导致这些变化。一种候选机制是培养基前额谷氨酸（GLU）的改变 GABA，最近都涉及MDD，也是一个关键的风险因素 MDD的发展，压力。但是，迄今为止，尚无研究对GLU和GABA的体内评估响应MDD或健康对照中的社会心理压力的功能。为了解决这个问题，K99 该应用程序的阶段提出以下培训目标。首先，为了发展技术技能需要在体内评估GLU和GABA，候选人将从J. Eric博士那里学习MR光谱技术。 Jensen（K99 Co-Mentor）和DostOngür博士（顾问）。这将涉及组合的完成 MRS/FMRI研究将探讨基线GLU和GABA功能与大胆fMRI之间的关系在健康参与者的增强学习过程中的信号。其次，候选人将加深他了解GLU和GABA功能在通过与博士博士的定向阅读中奖励处理中的作用肯特·贝里奇（Kent Berridge）（顾问）及其与情绪障碍的病理生理学有关 Ongür博士监督的读物。第三，他将基于他发展的行为建模技巧通过应用增强学习范式和相关Q学习模型的研究生院分析，该分析将由Michael Frank博士（顾问）监督；候选人还将参加弗兰克博士实验室会议每月以及他的课程“计算认知神经科学”。最后，候选人将在他的主要导师迭戈·比萨加利（Diego Pizzagalli）博士的指导和监督集成多模式成像数据，实验室压力源的设计和分析，并为开发独立实验室。在独立阶段，另外两个多模式成像提出了将MRS的GLU和GABA功能评估与fMRI的测量结果相结合的研究强化在心理社会压力源之前和之后学习。这些研究中的第一项将集中在在健康对照中，第二个将包括一个患有MDD和匹配对照的患者样本。通过使用以两个主要神经递质的方式使用多模式成像，这是一个前应力操纵并包括对照组和MDD患者，拟议的研究将提供重要的新见解 GLU和GABA功能在MDD中奖励处理定义的病理生理学中的作用。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Network analysis of depression and anxiety symptom relationships in a psychiatric sample.

DOI：
10.1017/s0033291716002300
发表时间：
2016-12
期刊：
Psychological medicine
影响因子：
6.9
作者：
Beard C;Millner AJ;Forgeard MJ;Fried EI;Hsu KJ;Treadway MT;Leonard CV;Kertz SJ;Björgvinsson T
通讯作者：
Björgvinsson T

Corticoinsular circuits encode subjective value expectation and violation for effortful goal-directed behavior.

DOI：
10.1073/pnas.1800444115
发表时间：
2018-05-29
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
Arulpragasam AR;Cooper JA;Nuutinen MR;Treadway MT
通讯作者：
Treadway MT

Effort-Based Decision-Making Paradigms for Clinical Trials in Schizophrenia: Part 1—Psychometric Characteristics of 5 Paradigms.

DOI：
10.1093/schbul/sbv089
发表时间：
2015-09
期刊：
Schizophrenia bulletin
影响因子：
6.6
作者：
L. F. Reddy;W. Horan;D. M. Barch;Robert W. Buchanan;E. Dunayevich;James M. Gold;Naomi Lyons;S. Marder;M. Treadway;J. Wynn;Jared W. Young;Michael F. Green
通讯作者：
L. F. Reddy;W. Horan;D. M. Barch;Robert W. Buchanan;E. Dunayevich;James M. Gold;Naomi Lyons;S. Marder;M. Treadway;J. Wynn;Jared W. Young;Michael F. Green

Isolating biomarkers for symptomatic states: considering symptom-substrate chronometry.