Hemispheric asymmetry in stress processing in rat prefrontal cortex and the role of mesocortical dopamine

The prefrontal cortex (PFC) is known to play an important role not only in the regulation of emotion, but in the integration of affective states with appropriate modulation of autonomic and neuroendocrine stress regulatory systems. The present review highlights findings in the rat which helps to elucidate the complex nature of prefrontal involvement in emotion and stress regulation. The medial PFC is particularly important in this regard and while dorsomedial regions appear to play a suppressive role in such regulation, the ventromedial (particularly infralimbic) region appears to activate behavioral, neuroendocrine and sympathetic autonomic systems in response to stressful situations. This may be especially true of spontaneous stress-related behavior or physiological responses to relatively acute stressors. The role of the medial PFC is somewhat more complex in conditions involving learned adjustments to stressful situations, such as the extinction of conditioned fear responses, but it is clear that the medial PFC is important in incorporating stressful experience for future adaptive behavior. It is also suggested that mesocortical dopamine plays an important adaptive role in this region by preventing excessive behavioral and physiological stress reactivity. The rat brain shows substantial hemispheric specialization in many respects, and while the right PFC is normally dominant in the activation of stress-related systems, the left may play a role in countering this activation through processes of interhemispheric inhibition. This proposed basic template for the lateralization of stress regulatory systems is suggested to be associated with efficient stress and emotional self-regulation, and also to be shaped by both early postnatal experience and gender differences.     

Dissecting adrenal and behavioral responses to stress by targeted gene inactivation in mice

To define the molecular pathways modulating adrenal and behavioral responses to stress, we have generated mice with inactivation of hypothalamic neuropeptides and signaling pathways. Studies in mice deficient in corticotropin-releasing hormone (CRH) have revealed the essential role for CRH in adrenal glucocorticoid production in response to many physiological and psychological stressors. Immune system activation in CRH-deficient mice provides a unique exception to the necessity for CRH in stimulating adrenal glucocorticoid production. By analyzing mice deficient in interleukin-6 (IL-6) and CRH, we find that restoration of glucocorticoid output with inflammation is largely mediated by dysregulated IL-6 production. Current studies focus on identifying cellular and gene targets by which glucocorticoids regulate immune system function. In contrast to impaired adrenocortical responses to stress, CRH-deficient mice exhibit normal behavioral responses to stress. To determine signaling pathways that may contribute to the behavioral responses to stress, we have generated and analyzed mice deficient in adenylyl cyclase type 8 (AC8). AC8 deficient mice have intact adrenocortical responses to stress, but an inability to undergo stress-induced alterations in behavior.     

The effect of "stress hormones" on emotional sensitivity]

Stress is associated with an increased secretion of hormones from the hypothalamus-pituitary-adrenal-axis (HPA-axis). Once released into the blood stream they induce a number of adaptive changes that may also have pertinence to brain functions, resulting, for example in alterations of mood. To provide evidence for a mediation of mood changes by stress related hormone secretion, the influences of a short-term administration of hormones of the HPA-axis on mood and activation were assessed in a total of 182 healthy men (aged between 18 and 34 years in 7 experiments). Effects of intravenously administered hormones on self-perceived mood and activation were assessed by a standardized adjective checklist (Eigenschaftsw?rterliste) in placebo-controlled, double-blind experiments during rest. Results indicated no effects following corticotropin releasing-hormone or cholecystokinin, but specific effects resulted after vasopressin, oxytocin, ACTH-related hormones, and cortisol. Vasopressin and oxytocin increased activation and attenuated arousal and anger, ACTH-related hormones increased sensitivity and diminished extraversion, while cortisol increased activation and concentration. It is concluded that hormones of the HPA-axis specifically affect mood and activation. The pattern of hormonal changes in mood may have adaptive functions by preparing for behavioral and cognitive coping with stress.     

Depression and stressful environments: identifying gaps in conceptualization and measurement

Background and Objectives: Stress is well known as a trigger of depressive reactions, fear, anxiety, and behavioral disorders. However, there are many gaps in the conceptualization and measurement of environmental stress. Results: Exciting developments in the neuroscience of stress have increasingly expanded our knowledge of mechanisms by which stress may affect emotional and behavioral adjustment. Ironically, environmental stress has often been a silent player in human studies of stress processes. There is a significant need for increased efforts to include environmental stress variables in models of internalizing and other disorders. Measurement and conceptualization issues are prominent, and this article makes the case for improved methods of measuring acute, chronic, and early life stress, and for additional conceptualization of the dynamically changing and bidirectional effects of stress on disorder over time. Conclusions: There is a critical need for greater focus on and better measurement of the environment and its impact on emotional and other disorders, with emphasis on developmentally informed hypotheses. Empirical findings and new perspectives may contribute enormously to our understanding of normal and abnormal outcomes, and also to the challenge of effective interventions to promote mental health and optimal functioning.     

Local crime as a natural hazard: Implications for understanding the relationship between disorder and fear of crime

Summary We have suggested the following: Local crimes and natural hazards share several objective similarities and similarities in how they are perceived. Although local crimes and natural hazards are clearly different in numerous respects, these points of analogy suggest that in several ways responses to local disorder may be similar to responses to hazards. If this is the case, processes used to explain how persons respond to disasters may help explain a recurrent puzzle in the responses to disorder literature: the loose linkages between local disorder levels and fear levels.Future research needs include developing a fuller understanding of how other contextual factors mediate or moderate the processes discussed here, how these processes are related to and may mediate behavioral responses to crime, and how these behaviors in turn influence perceptions. We have suggested here that anticrime behaviors may result in some disadaptation to the threat, thereby elevating fear, and have provided evidence to that effect. In addition it is important to ascertain how the points of analogy between crime as a natural hazard and crime as an environmental stressor may be melded to develop more insight than afforded by either perspective considered singly. The heuristic developed here suggests some additional considerations for policy makers involved in anticrime or fear reduction programs.Irv Altman, Paul Bell, Joan McCord, Aaron Podolefsky, and Carol Werner provided helpful and encouraging comments on earlier drafts.     

恐惧与厌恶情绪图片系统的编制：基于两种情绪的区分

基于恐惧与厌恶情绪刺激材料界定模糊的问题,实验一在总结前人研究中实验材料方面混淆恐惧和厌恶的基础上,通过问卷法完成了对恐惧与厌恶图片系统初步的搜集、整理工作;实验二通过进一步测评得到了具有良好信度的恐惧与厌恶情绪图片系统,图片系统中的恐惧与厌恶情绪很好的分离,且图片系统中动物、场景、物体三类图片的恐惧、厌恶程度均存在显著差异,可适用于需要不同种类情绪刺激的具体应用性研究。     

恐惧与厌恶情绪图片系统的编制：基于两种情绪的区分

基于恐惧与厌恶情绪刺激材料界定模糊的问题,实验一在总结前人研究中实验材料方面混淆恐惧和厌恶的基础上,通过问卷法完成了对恐惧与厌恶图片系统初步的搜集、整理工作;实验二通过进一步测评得到了具有良好信度的恐惧与厌恶情绪图片系统,图片系统中的恐惧与厌恶情绪很好的分离,且图片系统中动物、场景、物体三类图片的恐惧、厌恶程度均存在显著差异,可适用于需要不同种类情绪刺激的具体应用性研究。     

HPA-Axis Activation as a Key Moderator of Childhood Trauma Exposure and Adolescent Mental Health

Individual differences in a child’s sensitivity to stress may influence whether youth exposed to trauma develop symptoms of psychopathology. We examined the interaction between HPA-axis reactivity to an acute stressor and exposure to different types of childhood trauma as predictors of mental health symptoms in a sample of youth. Youth (n?=?121, ages 9–16; 47% female) completed a standardized stress task, including 5 post-stress salivary cortisol samples. Parents also completed the Child Behavior Checklist as a measure of child internalizing and externalizing symptoms in the past month, and completed the Early Trauma Inventory (ETI) as a measure of their child’s trauma exposure. More emotional abuse and non-intentional trauma were associated with greater internalizing symptoms. Youth exposed to physical abuse who demonstrated slower HPA-axis reactivity had elevated internalizing and externalizing symptoms. Youth exposed to emotional abuse or non-intentional traumatic events who demonstrated faster HPA-axis reactivity had elevated internalizing and externalizing symptoms. Profiles of exaggerated or attenuated HPA-axis reactivity to acute stress may be risk factors for psychopathology in children facing different stressful social environments.     

“非典”流行期民众常见的心理应激反应与心理干预

该文介绍了传染性非典型性肺炎（严重的急性呼吸综合征,SARS）急性流行期我国民众较常见的心理应激反应,包括焦虑和恐惧、愤怒和怨恨以及抑郁等情绪反应,认知反应,自我防御反应和生理反应,描述了人们面对SARS威胁时的应对策略;探讨了当前影响民众心理反应的诸种因素,包括刺激事件或刺激情境的性质与特点,对事物的态度和认识评价,应对挑战的能力与应对方式,以及心理社会环境和人格特征等;指出了心理干预应当遵循的四个原则和多种形式,说明了6种心理干预的具体措施和方法。     

Inspired by Hope,Motivated by Envy: Comparing the Effects of Discrete Emotions in the Process of Social Comparison to Media Figures

Despite considerable research and theorizing regarding the process of social comparison, limited attention has been given to the role of discrete emotions in this context, particularly as they may influence the behavioral responses resulting from comparison to similar others. In the context of cosmetic surgery makeover programs, we explore how discrete emotions may mediate the effects of social comparison on behavior and how different emotions, envy and hope in particular, may differentially relate to behavioral motivation. Based on the survey responses of 236 female students, results suggest that social comparison to media figures correlates with a range of emotional responses as well as with behavioral motivation for invasive cosmetic enhancements. Envy maintained a significantly greater association with behavioral motivation than hope or any other emotional response. Further, mediational analyses were consistent with the argument that envy, but not hope, mediates the social comparison–behavioral motivation relationship. The relationship between character identification and social comparison, as well as processes associated with downward social comparison, are also explored. This research helps illuminate the driving mechanism for social comparison's effects on behavior and has implications for better understanding how media exposure may stimulate this process.     

缰核在抑郁症中的作用:研究和治疗的新途径

缰核是哺乳动物神经系统中连接前脑和中脑的重要节点,这一古老的核团因其与抑郁症的密切联系,近来获得国内外研究者的关注.缰核接受来自边缘系统、基底神经节等的传入信号,向下投射到中脑5-羟色胺系统和多巴胺系统.在应激条件下缰核免疫活动增强,向下游的投射信号增强,以此调节单胺类递质释放,参与抑郁症的发病机制,并且参与抗抑郁治疗的起效途径.这些证据提示缰核在抑郁症中具有重要作用,将成为研究和治疗的新途径.未来研究应从缰核与上下游核团的神经联系、与丘脑-垂体-肾上腺轴的相互影响、以及与免疫激活的交互作用等方面进一步探索,为研究抑郁症病理机制和治疗方法提供线索.     

呼吸道传染病疫情背景下的民众社交距离保持行为

自COVID-19疫情爆发以来,疫情背景下的社交距离保持行为成为了一个受到关注的新兴问题。民众遵守社交限制措施和主动扩大社交距离对遏制呼吸道传染病疫情非常重要,而这些社交距离保持行为受到疫情情境、疫情相关认知和情绪、社会文化背景以及个体心理特质影响。疫情情境方面,疫情严重性与民众报告的社交距离保持行为并非简单的线性相关,可能受到时间进程的调节;社交距离保持行为还存在地区特异性,疫情首发地民众遵守社交距离保持意愿和行为更主动、更持久。其次,疫情相关认知和情绪方面,疫情知识,感知到的疫情风险性、严重性、可控性和主观规范,以及恐惧、担忧等负面情绪均可预测社交距离保持行为。第三,作为社会文化背景的不确定性回避程度、个人主义-集体主义价值观等因素,可能对民众在疫情背景下社交距离保持行为及心理产生直接或间接的影响。最后,个体认知特征中的自我控制、认知需求水平与自我效能感可正向预测社交距离保持行为,显示出社交距离保持行为中需要个体主动努力做出决策的部分;情绪动机特质中的健康风险回避倾向、厌恶敏感性、亲社会动机,社会认知视角下对科学和政府机构的信任,均可影响社交距离保持行为,并且人际信任水平对社交距离保持行为模式时间进程具有调节作用。 上述社交距离保持行为影响因素的研究发现,可基于计划行为理论、保护动机理论和行为免疫系统理论进行解释。其中,计划行为理论和保护动机理论强调个体对行为情境、成本、结果、他人反应的有意识感知、计算等高认知资源需求的活动。而行为免疫系统理论主要强调在传染病威胁下自动化水平的感知和行为改变。三个理论从有意识加工和自动化加工两个层面共同支持疫情背景下社交距离保持行为存在威胁管理机制,是目前社交距离保持行为领域最受关注的研究方向。其次,保护动机理论所强调的应对评估、计划行为理论中的知觉行为控制要素,以及近期研究所发现的自我效能感、自我控制、认知需求水平对社交距离保持行为的预测,均提示可能还存在独立于威胁管理机制之外的自我效能感机制影响社交距离保持行为。最后,计划行为理论所强调的主观规范要素有利于解释社会文化背景及亲社会动机、社会信任等因素的影响,结合近期有关疫情污名化和社会分类相关研究进展,我们提出,疫情背景下的社交距离保持行为可能还受到社会认同机制的影响,整合社会认同理论和计划行为理论,有助于更综合地体现个体与群体、理性和非理性因素的作用。未来研究应进一步考察情绪认知过程及其与社会文化背景和个体心理特质的交互作用,构建双系统模型,例如基于熟虑-冲动双系统模型,整合社会认同理论和计划行为理论,结合追踪及实验研究,明确各影响因素之间的因果关系,检验疫情背景下社交距离保持行为的内在机制。     

Role of stress, corticotrophin releasing factor (CRF) and amygdala plasticity in chronic anxiety

Stress initiates a series of neuronal responses that prepare an organism to adapt to new environmental challenges. However, chronic stress may lead to maladaptive responses that can result in psychiatric syndromes such as anxiety and depressive disorders. Corticotropin-releasing factor (CRF) has been identified as a key neuropeptide responsible for initiating many of the endocrine, autonomic and behavioral responses to stress. The amygdala expresses high concentrations of CRF receptors and is itself a major extrahypothalamic source of CRF containing neurons. Within the amygdala, the basolateral nucleus (BLA) has an important role in regulating anxiety and affective responses. During periods of stress, CRF is released into the amygdala and local CRF receptor activation has been postulated as a substrate for stress-induced alterations in affective behavior. Previous studies have suggested that synaptic plasticity in the BLA contributes to mechanisms underlying long-term changes in the regulation of affective behaviors. Several studies have shown that acute glutamate receptor-mediated activation, by either GABA-mediated disinhibition or CRF-mediated excitation, induces long-term synaptic plasticity and increases the excitability of BLA neurons. This review summarizes some of the data supporting the hypotheses that stress induced plasticity within the amygdala may be a critical step in the pathophysiology of the development of chronic anxiety states. It is further proposed that such a change in the limbic neural circuitry is involved in the transition from normal vigilance responses to pathological anxiety, leading to syndromes such as panic and post-traumatic stress disorders.     

Exploration in outbred mice covaries with general learning abilities irrespective of stress reactivity, emotionality, and physical attributes

Across multiple learning tasks (that place different sensory, motor, and information processing demands on the animals), we have found that the performance of mice is commonly regulated by a single factor ("general learning") that accounts for 30-40% of the variance across individuals and tasks. Furthermore, individuals' general learning abilities were highly correlated with their propensity to engage in exploration in an open field, a behavior that is potentially stress-inducing. This relationship between exploration in the open field and general learning abilities suggests the possibility that variations in stress sensitivity/responsivity or related emotional responses might directly influence individuals' general learning abilities. Here, the relationship of sensory/motor skills and stress sensitivity/emotionality to animals' general learning abilities were assessed. Outbred (CD-1) mice were tested in a battery of six learning tasks as well as 21 tests of exploratory behavior, sensory/motor function and fitness, emotionality, and stress reactivity. The performances of individual mice were correlated across six learning tasks, and the performance measures of all learning tasks loaded heavily on a single factor (principal component analysis), accounting for 32% of the variability between animals and tasks. Open field exploration and seven additional exploratory behaviors (including those exhibited in an elevated plus maze) also loaded heavily on this same factor, although general activity, sensory/motor responses, physical characteristics, and direct measures of fear did not. In a separate experiment, serum corticosterone levels of mice were elevated in response to a mild environmental stressor (confinement on an elevated platform). Stress-induced corticosterone levels were correlated with behavioral fear responses, but were unsystematically related to individuals' propensity for exploration. In total, these results suggest that although general learning abilities are strongly related to individuals' propensity for exploration, this relationship is not attributable to variations in sensory/motor function or the individuals' physiological or behavioral sensitivity to conditions that promote stress or fear.     

分类和概念对恐惧泛化的影响机制

恐惧泛化与多种焦虑障碍的病理基础密切相关。例如创伤后应激障碍个体往往持续地逃避与创伤事件有关的刺激,遭受着创伤痛苦折磨。本文在厘清知觉辨别与恐惧泛化关系的基础上,着力于高级认知过程(分类与概念相似性、典型性和人工概念)对恐惧泛化的影响,回顾了恐惧泛化的相关神经机制,并揭示恐惧泛化对焦虑障碍患者的临床治疗启示。未来研究应将知觉和高级认知维度的恐惧泛化进行整合研究,同时扩充恐惧习得和泛化的神经回路,以促进人类恐惧泛化更深入的研究。     

From acquisition to consolidation: on the role of brain-derived neurotrophic factor signaling in hippocampal-dependent learning

One of the most rigorously investigated problems in modern neuroscience is to decipher the mechanisms by which experience-induced changes in the central nervous system are translated into behavioral acquisition, consolidation, retention, and subsequent recall of information. Brain-derived neurotrophic factor (BDNF) has recently emerged as one of the most potent molecular mediators of not only central synaptic plasticity, but also behavioral interactions between an organism and its environment. Recent experimental evidence indicates that BDNF modulates synaptic transmission and plasticity by acting across different spatial and temporal domains. BDNF signaling evokes both short- and long-term periods of enhanced synaptic physiology in both pre- and postsynaptic compartments of central synapses. Specifically, BDNF/TrkB signaling converges on the MAP kinase pathway to enhance excitatory synaptic transmission in vivo, as well as hippocampal-dependent learning in behaving animals. Emerging concepts of the intracellular signaling cascades involved in synaptic plasticity induced through environmental interactions resulting in behavioral learning further support the contention that BDNF/TrkB signaling plays a fundamental role in mediating enduring changes in central synaptic structure and function. Here we review recent literature showing the involvement of BDNF/TrkB signaling in hippocampal-dependent learning paradigms, as well as in the types of cellular plasticity proposed to underlie learning and memory.     

A model of amygdala–hippocampal–prefrontal interaction in fear conditioning and extinction in animals

Empirical research has shown that the amygdala, hippocampus, and ventromedial prefrontal cortex (vmPFC) are involved in fear conditioning. However, the functional contribution of each brain area and the nature of their interactions are not clearly understood. Here, we extend existing neural network models of the functional roles of the hippocampus in classical conditioning to include interactions with the amygdala and prefrontal cortex. We apply the model to fear conditioning, in which animals learn physiological (e.g. heart rate) and behavioral (e.g. freezing) responses to stimuli that have been paired with a highly aversive event (e.g. electrical shock). The key feature of our model is that learning of these conditioned responses in the central nucleus of the amygdala is modulated by two separate processes, one from basolateral amygdala and signaling a positive prediction error, and one from the vmPFC, via the intercalated cells of the amygdala, and signaling a negative prediction error. In addition, we propose that hippocampal input to both vmPFC and basolateral amygdala is essential for contextual modulation of fear acquisition and extinction. The model is sufficient to account for a body of data from various animal fear conditioning paradigms, including acquisition, extinction, reacquisition, and context specificity effects. Consistent with studies on lesioned animals, our model shows that damage to the vmPFC impairs extinction, while damage to the hippocampus impairs extinction in a different context (e.g., a different conditioning chamber from that used in initial training in animal experiments). We also discuss model limitations and predictions, including the effects of number of training trials on fear conditioning.     

The Role of Emotional Distress Tolerance on Fear Responding in a Heights-Fearful Sample: Perceived Versus Actual Behavior

Emotional distress tolerance (EDT)—or the ability to withstand negative emotional states—is considered a transdiagnostic risk factor for psychopathology. Although EDT is theorized to play a role in anxiety development and maintenance, research aiming to delineate the relationship between anxiety and EDT is lacking. The current study tested whether self-reported EDT predicted self-reported and actual avoidance in the presence of feared stimuli using a heights-fearful sample. Moreover, the study tested whether EDT predicted other in-the-moment fear responses, such as peak anxiety, anxious cognitions, and bodily sensations. Participants (N = 128) completed questionnaires assessing fear of heights, negative affect, anxious cognitions, and bodily sensations, as well as two heights behavioral avoidance tasks (BATs). Results demonstrated that EDT did not predict actual avoidance or other in-the-moment fear responses, except for peak anxiety in one BAT. However, EDT predicted self-reported avoidance of heights beyond fear of heights and negative affect. Taken together, results suggest that perception of ability to tolerate emotional distress predicts perception of avoidance of heights, but not actual avoidance of heights or reactions to heights (with the exception of peak anxiety in one BAT). Given these findings, self-reported EDT may not adequately predict how individuals react in anxiety-provoking situations.     

Protein kinase a in major depression: the link between hypothalamic-pituitary-adrenal axis hyperactivity and neurogenesis

The latest and most generative biological theories of major depression center on two major hypotheses. The first focuses on the concept that hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis leads to many of the pathological changes in the brain that accompany major depression. The second posits that neurogenesis leads to the repair of depression-related injuries. These two hypotheses are complementary: the former alludes to the etiology or consequences of depression, while the latter suggests mechanisms of antidepressant action. Significant crosstalk occurs between these two systems at many levels. Protein kinase A (PKA) may play an important role in this crosstalk at the intracellular level of signaling cascades. PKA is involved in the formation of long-term potentiation and fear conditioning in response to stress. Chronic stress leads to the suppression of hippocampal activity, which may cause the hyperactivity of the HPA axis during melancholic depression. PKA is also involved in the stimulation of hippocampal neurogenesis after antidepressant treatment. In theory, neurogenesis may lead to the restoration of hippocampal function, and this may be the mechanism that leads to antidepressant-mediated normalization of HPA hyperactivity. Thus, PKA is active during processes that potentially lead to depression and other processes that lead to the resolution of the illness. These opposing processes may be mediated by separate PKA isozymes that activate two distinct pathways. This review highlights the dual role of this enzyme in two biological hypotheses pertaining to depression and its treatment.