权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

The Psychophysiology Of Fear And Anxiety

恐惧和焦虑的心理生理学

基本信息

批准号：
7735153
负责人：
Christian Grillon
金额：
$ 165.37万
依托单位：
NATIONAL INSTITUTE OF MENTAL HEALTH
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/7735153
关键词：
Acute Adult Adverse effects Affect Affective Amygdaloid structure Animal Model Animals Anterior Anti-Anxiety Agents Anxiety Anxiety Disorders Area Base of the Brain Basic Science Behavior Behavioral Biological Biological Markers Brain Characteristics Child Chronic Citalopram Classification Comorbidity Condition Corticotropin-Releasing Hormone Cues Data Data Sources Development Diagnostic Diagnostic and Statistical Manual Diffuse Disease Distal Emotional Etiology Experimental Models Face Family Fertilization Fright Functional Magnetic Resonance Imaging Functional disorder Future General Population Goals Hippocampus (Brain)Hormones Human Hydrocortisone Individual Intervention Laboratories Learning Left Limbic System Magnetoencephalography Maps Measures Mediating Mediation Memory Mental disorders Modeling Movement Neurobiology Neurosciences Panic Disorder Pathologic Patients Pattern Performance Pharmaceutical Preparations Physiological Post-Traumatic Stress Disorders Prefrontal Cortex Process Psychopharmacology Psychophysiology Reflex action Research Retrieval Risk Rodent Science Selective Serotonin Reuptake Inhibitor Shock Signal Transduction Social Phobia Specificity Staging Stress Structure Structure of terminal stria nuclei of preoptic region Testing Translational Research Variant Water Week Work analog base classical conditioning clinically relevant conditioned fear conditioning disorder subtype dorsal raphe nucleus drug discovery endophenotype frontal lobe genetic epidemiology human subject inhibitor/antagonist morris water maze neural circuit neuroimaging psychologic psychopharmacologic relating to nervous system research study response reuptake social stressor theories tool translational approach virtual virtual reality

项目摘要

Our objective is to determine the extent to which different aspects of conditioned fear are relevant to features of particular forms of normal and abnormal anxiety in humans. We make a distinction between two forms of aversive states, fear and anxiety, with a particular focus on anxiety. Operationally, fear is defined as a phasic aversive state induced by a proximal and identifiable threat, whereas anxiety is a more sustained form of response focused on potential distal or future threats that are not clearly identifiable. Research in animals suggests that these two forms of aversive states can be modeled by cue and context conditioning, respectively. Experimental models: We focus on developing models of anxiety based on their presumed clinical relevance. In the last several years, we used virtual reality to model cue and context conditioning. In this experiment, fear and anxiety are assessed based on physiological responses. We recently introduced a new experiment, a virtual reality analogue of the Morris water maze. In this task, anxiety is measured based on behavior. The Morris water task also presents important procedural differences compared to context conditioning. The shock is uncontrollable in context conditioning, whereas stressor duration is contingent on subjects behavior (i.e., reaching the hidden platform) in the Morris water maze. Psychopharmacology: We have demonstrated that contextual anxiety is increased by acute citalopram and reduced by 2-week treatment with the serotoninergic reuptake inhibitor (SSRI), citalopram. These results are consistent with the effects of SSRI in patients. The anxiolytic effects of SSRI are dependent on a chronic administration of the drug. Initially, SSRI can be anxiogenic in some patients. Preliminary results suggest that short-term treatment with hydrocortisone is anxiolytic. These results are significant because cortisol effect on anxiety is believed to be mediated via its action on the consolidation and retrieval of emotional memories. Our results suggest a direct effect on the expression of anxiety. One possibility is that cortisol potentiates the effect of the stress hormone corticotrophin releasing factor in limbic system structures such as the bed nucleus of the stria terminalis. Behavioral studies in patients: We showed that individuals with panic disorders have elevated contextual anxiety, but normal cued fear. Preliminary results from ongoing studies suggest a similar pattern of responses in PTSD but not in social phobia. These results suggest that patients with panic disorder and PTSD may share a common vulnerability to diffuse contextual threats. They also suggest that anxious patients are overly sensitive to unpredictable stressors. While patients with social anxiety disorder are not overly sensitive to non-specific stressors (e.g. mild shocks), they tend to form aversive Pavlovian associations with social stressors, suggesting that conditioning may be an etiological factor in this disorder. Neuroimaging: Using fMRI, we demonstrated that a different set of brain areas is activated by cue fear and contextual anxiety. In particular, context conditioning is associated with activation of a network encompassing the amygdala, hippocampus, parahihpocampal cortex, orbito frontal cortex, and subjenual anterior cingulate. These results are consistent with basic findings and rodents. Navigation in the Morris water maze was investigated with magnetoencephalography, with a special focus on the hippocampal and on parahippocampal theta oscillations. Two early peaks of left hippocampal and parahippocampal theta activity were observed during navigation to a hidden platform. Our results suggest that hippocampal and parahippocampal theta oscillations increased specifically under conditions in which spatial information is being encoded and/or retrieved rather than being elicited solely by virtual movements in general. There was also a linear relationship between hippocampal and parahippocampal theta responses and navigation performance on the vMWM, consistent with the interpretation that oscillatory activity is involved in spatial learning.

我们的目标是确定条件性恐惧的不同方面与人类正常和异常焦虑的特定形式的特征相关的程度。我们区分两种形式的厌恶状态，恐惧和焦虑，特别关注焦虑。在操作上，恐惧被定义为由近端和可识别的威胁引起的阶段性厌恶状态，而焦虑是一种更持续的反应形式，专注于潜在的远端或未来的威胁，这些威胁无法明确识别。对动物的研究表明，这两种形式的厌恶状态可以分别通过线索和语境条件反射来模拟。实验模型：我们专注于基于其假定的临床相关性开发焦虑模型。在过去的几年里，我们使用虚拟现实来模拟线索和情境条件反射。在这个实验中，恐惧和焦虑是根据生理反应来评估的。我们最近推出了一个新的实验，一个虚拟现实模拟莫里斯水迷宫。在这项任务中，焦虑是根据行为来衡量的。莫里斯水任务也提出了重要的程序相比，上下文条件反射的差异。在情境条件反射中，电击是不可控的，而应激持续时间取决于受试者的行为（即，到达隐藏的平台）在莫里斯水迷宫。精神药理学：我们已经证明，急性西酞普兰会增加背景焦虑，而西酞普兰治疗2周后会减少背景焦虑。这些结果与SSRI对患者的影响一致。SSRI的抗焦虑作用依赖于药物的长期给药。最初，SSRI在某些患者中可能是致焦虑的。初步结果表明，短期治疗氢化可的松是抗焦虑。这些结果是重要的，因为皮质醇对焦虑的影响被认为是通过其对情绪记忆的巩固和提取的作用来介导的。我们的研究结果表明，焦虑的表达有直接的影响。一种可能性是皮质醇增强了边缘系统结构（如终纹床核）中应激激素促肾上腺皮质激素释放因子的作用。对患者的行为研究：我们发现，惊恐障碍患者的情境焦虑升高，但正常的线索恐惧。正在进行的研究的初步结果表明，PTSD患者的反应模式类似，但社交恐惧症患者的反应模式不同。这些结果表明，惊恐障碍和PTSD患者可能有一个共同的脆弱性，以扩散上下文的威胁。他们还认为，焦虑的患者对不可预测的压力源过于敏感。虽然社交焦虑障碍患者对非特异性压力源（例如轻度电击）并不过分敏感，但他们倾向于与社会压力源形成厌恶的巴甫洛夫关联，这表明条件反射可能是这种疾病的病因。神经影像学：使用功能磁共振成像，我们证明了一组不同的大脑区域被线索恐惧和背景焦虑激活。特别是，情境条件反射与杏仁核、海马体、丘脑旁皮质、眶额叶皮质和下扣带回前扣带回的网络激活有关。这些结果与基本研究结果和啮齿动物一致。导航在Morris水迷宫进行了调查与脑磁图，特别关注海马和海马旁θ振荡。在导航到隐藏平台的过程中，观察到左侧海马和海马旁theta活动的两个早期峰值。我们的研究结果表明，海马和海马旁θ振荡增加的条件下，空间信息被编码和/或检索，而不是仅仅引起一般的虚拟运动。也有海马和海马旁θ反应和导航性能的vMWM之间的线性关系，振荡活动参与空间学习的解释是一致的。

项目成果

期刊论文数量（31）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Comments on Fearful and sexual pictures not consciously seen modulate the startle reflex in human beings.

对无意识看到的可怕和性图片的评论调节了人类的惊吓反射。

DOI：
10.1016/j.biopsych.2006.12.026
发表时间：
2007
期刊：
Biological psychiatry
影响因子：
10.6
作者：
Grillon,Christian;Cornwell,Brian
通讯作者：
Cornwell,Brian

Hydrocortisone impairs hippocampal-dependent trace eyeblink conditioning in post-traumatic stress disorder.

氢化可的松会损害创伤后应激障碍中海马依赖性的微量眨眼调节。

DOI：
10.1038/sj.npp.1300843
发表时间：
2006
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
0
作者：
Vythilingam,Meena;Lawley,Megan;Collin,Carlos;Bonne,Omer;Agarwal,Rajni;Hadd,Kayleen;Charney,DennisS;Grillon,Christian
通讯作者：
Grillon,Christian

Startle potentiation in rapidly alternating conditions of high and low predictability of threat.

在威胁的高可预测性和低可预测性快速交替的条件下，惊吓增强。