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The Psychophysiology Of Fear And Anxiety

恐惧和焦虑的心理生理学

基本信息

批准号：
7969369
负责人：
Christian Grillon
金额：
$ 234.7万
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/7969369
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 Clinical Cognitive Comorbidity Corticotropin-Releasing Hormone Cues Data Sources Defense Mechanisms Development Diagnostic Diagnostic and Statistical Manual of Mental Disorders Diffuse Disease Distal Emotional Etiology Event Experimental Models Family Family Study Fertilization Fright Functional Magnetic Resonance Imaging Functional disorder Future General Population Goals Hippocampus (Brain)Hormones Human Hydrocortisone Individual Insula of Reil Intervention Laboratories Limbic System Link Maps Measures Mediating Mediation Memory Mental disorders Modeling Moods Motor Neurobiology Neurosciences Panic Disorder Pathologic Patients Pattern Pharmaceutical Preparations Physiological Post-Traumatic Stress Disorders Prefrontal Cortex Procedures Process Psychopharmacology Psychophysiology Reflex action Reporting Research Retrieval Role Saccades 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 Work analog base classical conditioning clinically relevant conditioned fear conditioning disorder subtype dorsal raphe nucleus drug discovery endophenotype high risk improved inhibitor/antagonist morris water maze neural circuit neuroimaging psychologic relating to nervous system research study response reuptake social stressor theories tool translational approach treatment duration virtual reality

项目摘要

Our objective is to determine the extent to which different aspects of defense mechanisms and 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 treatment with the serotoninergic reuptake inhibitor (SSRI), citalopram, and reduced by 2-week treatment with the same drug. These results are consistent with the effects of SSRI treatment in patients. The anxiolytic effects of SSRI are dependent on a chronic administration of the drug. Initially, SSRI can be anxiogenic in some patients. We recently examined the role of cortisol in fear and anxiety. Acute hydrocortisone treatment was found to be anxiolytic. These results are significant because cortisol's 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. We also found that 4-day treatment is anxiolytic. This effect was unexpected, but is not inconsistent with observation that short-term treatments with cortisol can improve mood. Behavioral studies in patients: We showed that individuals with panic disorders have elevated contextual anxiety, but normal cued fear. We recently reported a similar pattern of responses in Posttraumatic stress disorder 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 functional Magnetic Resonance Imaging, we demonstrated that predictable and unpredictable aversive events activate common and distinct brain areas. Notably, the amygdala and anterior insula is activated by both types of threats, whereas the bed nucleus of the stria terminalis is activated uniquely during unpredictable shocks, probably because unpredictable shocks evoke a sustained state of anxiety. In contrast, the subgenual anterior cingulate is activated during the predictable condition. This structure has been shown to mediate inhibition of fear in a number of procedures in humans and animals. Because predictable shocks are less stressful than unpredictable shocks, the subgenual anterior cingulate may be involved in reducing anxiety in the predictable condition compared to the unpredictable condition. We are also studying how anxiety affects cognitive-attentional processes. Defining cognitive-attentional changes that are central to anxiety may provide important links between brain dysfunction and clinical phenomenology. For example, we examined the effect of unsignaled shocks on reflexive vs. controlled oculo-motor responses (i.e., pro- vs. anti-saccades). Our findings revealed that anxiety promoted reflexive responding at the expense of more controlled responding.

我们的目标是确定防御机制和条件性恐惧的不同方面与人类特定形式的正常和异常焦虑的特征相关的程度。我们区分两种形式的厌恶状态：恐惧和焦虑，特别关注焦虑。从操作上讲，恐惧被定义为由近端且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无法明确识别的威胁。对动物的研究表明，这两种形式的厌恶状态可以分别通过提示和情境调节来建模。实验模型：我们专注于根据假定的临床相关性开发焦虑模型。在过去的几年中，我们使用虚拟现实来模拟提示和情境调节。在这个实验中，根据生理反应评估恐惧和焦虑。我们最近推出了一项新实验，即莫里斯水迷宫的虚拟现实模拟。在此任务中，焦虑是根据行为来测量的。与上下文调节相比，莫里斯水任务还呈现出重要的程序差异。在情境调节中，电击是无法控制的，而压力源的持续时间取决于莫里斯水迷宫中受试者的行为（即到达隐藏的平台）。精神药理学：我们已经证明，使用血清素能再摄取抑制剂（SSRI）、西酞普兰进行急性治疗会增加情境焦虑，而使用相同药物两周治疗会减少情境焦虑。这些结果与 SSRI 治疗患者的效果一致。 SSRI 的抗焦虑作用取决于该药物的长期给药。最初，SSRI 可能会对某些患者产生焦虑。我们最近研究了皮质醇在恐惧和焦虑中的作用。发现急性氢化可的松治疗具有抗焦虑作用。这些结果很重要，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检索的作用来介导的。我们的结果表明对焦虑的表达有直接影响。一种可能性是皮质醇增强了边缘系统结构（例如终纹床核）中应激激素促肾上腺皮质激素释放因子的作用。我们还发现 4 天的治疗具有抗焦虑作用。这种效果是出乎意料的，但与短期皮质醇治疗可以改善情绪的观察结果并不矛盾。对患者的行为研究：我们发现，患有恐慌症的人的情境焦虑程度较高，但正常情况下会引发恐惧。我们最近报道了创伤后应激障碍中类似的反应模式，但社交恐惧症中却没有。这些结果表明，患有恐慌症和创伤后应激障碍的患者可能对弥漫性情境威胁有着共同的脆弱性。他们还表明，焦虑的患者对不可预测的压力源过于敏感。虽然社交焦虑症患者对非特异性压力源（例如轻微冲击）并不太敏感，但他们倾向于与社交压力源形成厌恶的巴甫洛夫关联，这表明调节可能是这种疾病的病因因素。神经影像学：利用功能性磁共振成像，我们证明可预测和不可预测的厌恶事件会激活常见和不同的大脑区域。值得注意的是，两种类型的威胁都会激活杏仁核和前岛叶，而终纹床核在不可预测的冲击期间会被独特地激活，这可能是因为不可预测的冲击会引起持续的焦虑状态。相反，膝下前扣带回在可预测的情况下被激活。这种结构已被证明可以在人类和动物的许多手术中介导恐惧的抑制。由于可预测的电击比不可预测的电击压力较小，因此与不可预测的情况相比，膝下前扣带回可能参与减少可预测情况下的焦虑。我们还在研究焦虑如何影响认知注意力过程。定义对焦虑至关重要的认知注意力变化可能会提供大脑功能障碍和临床现象学之间的重要联系。例如，我们检查了无信号电击对反射性与受控眼动反应（即支持眼跳与反眼跳）的影响。我们的研究结果表明，焦虑促进了反射性反应，但牺牲了更受控制的反应。