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Cerebral GABA and Fear Conditioning in PTSD

创伤后应激障碍 (PTSD) 中的大脑 GABA 和恐惧调节

基本信息

批准号：
8497753
负责人：
ISABELLE M ROSSO
金额：
$ 36.25万
依托单位：
MCLEAN HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-01 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8497753
关键词：
Abate Acute Affect Aminobutyric Acids Anterior Antiepileptic Agents Anxiety Area Behavior Behavioral Biological Markers Brain Brain Chemistry Brain region Cerebrum Chemicals Chronic Clinical Clinical Markers Conditioned Stimulus Data Detection Development Diagnosis Diagnostic Specificity Dimensions Disease Event Exposure to Extinction (Psychology)Failure Fright Functional Imaging Functional Magnetic Resonance Imaging Future Galvanic Skin Response Goals Hyperactive behavior Impairment Individual Insula of Reil Knowledge Laboratories Lead Learning Literature Magnetic Resonance Spectroscopy Maintenance Measures Mediating Mental disorders Methods Modeling National Institute of Mental Health Nature Neurobiology Neurons Neurotransmitters Patients Pharmacological Treatment Phase Phenotype Post-Traumatic Stress Disorders Prefrontal Cortex Protons Recording of previous events Recruitment Activity Relative (related person)Reporting Research Role Serum Severities Stimulus Strategic Planning Symptoms Technology Testing Trauma base biobehavior conditioned fear conditioning disease classification experience gamma-Aminobutyric Acid improved in vivo indexing neurochemistry neuronal excitability neuropsychiatry response

项目摘要

DESCRIPTION (provided by applicant): Post-traumatic stress disorder (PTSD) is a common and debilitating neuropsychiatric disorder in which an acute fear response to a traumatic event does not abate. This failure to recover from trauma is thought to be due at least in part to a deficit in learning not to fear situations and stimuli previously associated with the trauma. Thus, PTSD has been conceptualized as a disorder of 'fear conditioning' that involves a hyperresponsivity of neurons in brain regions mediating fear expression and a hyporesponsivity of neurons in brain regions mediating fear extinction. Moreover, converging evidence suggests that neurotransmitter alterations relate to these changes in neuron excitability, including alterations in the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). The proposed study will apply proton magnetic resonance spectroscopy (1H-MRS) methods to test hypotheses that PTSD is associated with altered GABA in two key brain areas: the ventromedial prefrontal cortex (VMPFC) and anterior insular cortex. We will also employ a well-validated fear conditioning paradigm to examine the hypothesis that VMPFC neurochemistry is associated with fear extinction deficits in PTSD. We will recruit 93 subjects comprised of 31 PTSD subjects, 31 trauma- exposed controls, and 31 healthy controls with no trauma history. Subjects will undergo single voxel high-field 1H-MRS using MEGAPRESS sequences that are optimized for detection and quantification of GABA, and have yielded encouraging preliminary data in these two brain regions. We will examine GABA levels in relation to PTSD diagnosis and symptoms, and in relation to behavioral indices of fear extinction recall and anxiety sensitivity. This will allow us to examine whether regional brain GABA is a marker of clinical and behavioral phenotypes of PTSD. Future research directions will include examination of whether GABA alterations in PTSD are sensitive to pharmacological treatment, and examination of their diagnostic specificity. Indeed, it is likely that GABA alterations represent biomarkers of behavioral phenotypes that are not only found in PTSD but also related psychiatric disorders. In this way, the goals of this research are relevant to priorities delineated in the NIMH strategic plan and RDoC initiative, particularly the identification of biobehavioral markers that may lead to the development of a biologically-valid psychiatric nosology.

描述（由申请人提供）：创伤后应激障碍（PTSD）是一种常见的、使人衰弱的神经精神障碍，其中对创伤性事件的急性恐惧反应没有减轻。这种从创伤中恢复的失败被认为至少部分是由于在学习不害怕先前与创伤有关的情况和刺激方面的缺陷。因此,