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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：
8994068
负责人：
Michael Tilghman Treadway
金额：
$ 24.9万
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 2017-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8994068
关键词：
Address Affective Age Amino Acids Aminobutyric Acids Anhedonia Animal Model 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 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 Neurotransmitters Operant Conditioning Participant Patient Self-Report Patients Performance Phase Prefrontal Cortex Preparation Prevalence Process Protons Psychological reinforcement Psychosocial Stress Punishment Reading Relative (related person)Research Rest Rewards Risk Factors Role Salivary Sampling Scanning Schools Signal Transduction Stress Supervision Symptoms Techniques Testing Training United States Work acute stress base behavior measurement cognitive neuroscience depressive behavior depressive symptoms design disability in vivo insight learned behavior meetings neuroimaging neurotransmission response reward processing skills social social stress stressor 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.

项目总结