Emotional dysfunction and childhood behavioral disturbance

情绪功能障碍和儿童行为障碍

• 批准号: 8342153
• 负责人: james r blair
• 金额: $ 124.81万
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 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/8342153
• 关键词: Accounting; Adolescent; Affective; Aggressive behavior; Amygdaloid structure; Anger; Association Learning; Attention deficit hyperactivity disorder; Behavior; Behavioral; Biological; Biological Markers; Bipolar Disorder; Brain; Childhood; Collaborations; Conduct Disorder; Data; Decision Making; Disease; Emotional; Empathy; Fright; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Guilt; Impairment; Individual; Intervention; Intervention Studies; Lateral; Learning; Link; Neurobiology; Pain; Parietal Lobe; Patients; Population; Prefrontal Cortex; Process; Protocols documentation; Psychological reinforcement; Punishment; Rewards; Rights; Risk; Series; Signal Transduction; Specific qualifier value; Suggestion; Treatment Efficacy; Work; Youth; base; callous unemotional trait; childhood bipolar disorder; cognitive neuroscience; economic cost; frontal lobe; meetings; outcome forecast; relating to nervous system; response; social

This project has established a series of core neuro-biological findings regarding the basis of Conduct Disorder (CD), particularly CD with Callous-Unemotional traits (reduced guilt and empathy); CD+CU: (i) CD+CU is associated with impaired processing of the fear of others and this impairment is associated with a reduced response by the amygdala to these expressions. This impairment is specific to fearful expressions and not seen to angry expressions. These data allow us to understand the basis of the empathy deficit in patients with this disorder. (ii) CD+CU is associated with impaired decision making and this impairment is associated with disruption in the representation of reinforcement information (how likely the action is to result in reward/ punishment) within ventromedial prefrontal cortex. These data allow us to understand the basis of the decision making impairment in patients with this disorder. (iii) Patients with Attention Deficit Hyperactivity Disorder (ADHD) but without CD show no difficulties in either their amygdala response to fearful expressions or the signaling of reinforcement information within ventromedial prefrontal cortex. This is important because CD and ADHD are often seen in the same youth. About 65% of our youth with CD+CU also meet criteria for ADHD. However, by showing that youth with ADHD, but without CD, show no problems in fearful expression or reinforcement processing, we can be sure that these difficulties are linked to CD+CU rather than the comorbid ADHD. In studies either recently completed or currently on-going, we have extended our earlier work by showing that: (i) The empathy deficits in CD+CU extend to the response to another individuals pain. These deficits are also related to reduced amygdala responses to another individuals pain. (ii) The decision making impairments are not only associated with deficiencies in the representation of reinforcement information within ventromedial prefrontal cortex but also with deficiencies within ventromedial frontal cortex and the caudate with respect to prediction error signaling. Prediction error signaling occurs in the brain when the individual unexpectedly receives reward or punishment. This signaling is important as it prompts rapid learning of the association between actions that elicited this reinforcement and the reinforcement itself. Poor prediction error signaling means poorer emotional learning and consequently poorer decision making. (iii) In collaboration with Dr. Leibenluft, we have shown that while youth with CD+CU and childhood bipolar disorder behaviorally show some similarities in their decision making impairment, the neural basis of these impairments are markedly different. CD+CU is associated with difficulties in ventromedial prefrontal cortex and caudate functioning with respect to the representation of reinforcement information and prediction error signaling. Childhood bipolar disorder is not. Instead, childhood bipolar disorder is associated with difficulties in organizing regions of lateral frontal and parietal cortex important for attentional control. Youth with CD+CU show no impairment in these capacities. Importantly, our empirical work distinguishing youth with CD+CU from youth with ADHD and youth with bipolar disorder allows us to further specify a neurobiological account of youth with CD+CU that is specific to this disorder. Moreover, this work allows us to determine which neural regions are disrupted in CD+CU and thus provides clues with respect to interventions that might benefit youth with CD+CU. Critically, this work has allowed us to identify objective bio-markers that can be used to assess treatment efficacy in this population. Currently, my group is developing protocols investigating two treatment interventions in youth with CD+CU using the fMRI biomarker tasks identified within this protocol to assess treatment efficacy.

该项目已经建立了有关行为障碍基础（CD）的一系列核心神经生物学发现，尤其是具有冷酷无情特征的CD（减少了内gui和同理心）； CD+CU： （i）CD+CU与对他人的恐惧的处理受损有关，这种障碍与杏仁核对这些表达的反应减少有关。 这种障碍是特定于恐惧的表情，而不是愤怒的表情。 这些数据使我们能够理解这种疾病患者的移情不足的基础。 （ii）CD+CU与决策受损有关，并且这种障碍与腹膜前额叶皮层内的增强信息的表示（行动导致奖励/惩罚的可能性）有关。 这些数据使我们能够了解该疾病患者的决策障碍的基础。 （iii）注意力缺陷多动障碍（ADHD）但没有CD的患者在杏仁核对可怕表情的反应或腹膜前额叶皮层中增强信息的信号传导都不困难。这很重要，因为CD和ADHD经常在同一年轻人中看到。我们约65％的CD+CU年轻人也符合多动症的标准。但是，通过显示ADHD的年轻人，但没有CD，就不会在恐惧表达或加强处理中表现出任何问题，我们可以确定这些困难与CD+CU相关，而不是合并症的ADHD。 在最近完成的研究或目前正在进行的研究中，我们通过表明： （i）CD+CU的同理心缺陷扩展到对他人痛苦的反应。 这些缺陷也与杏仁核对他人疼痛的反应减少有关。 （ii）决策障碍不仅与腹侧前额叶皮层内强化信息表示相关的缺陷，而且还与腹侧额叶皮层内的缺陷以及有关预测误差信号的持久性。 当个人意外收到奖励或惩罚时，预测错误信号发生在大脑中。 该信号很重要，因为它促使人们快速学习引起这种强化和强化本身的行动之间的关联。 差的预测错误信号意味着情绪学习较差，因此决策较差。 （iii）与Leibenluft博士合作，我们表明，尽管患有CD+CU和儿童双相情感障碍的青年在决策障碍中表现出一些相似之处，但这些障碍的神经基础明显不同。 CD+CU与腹侧前额叶皮层的困难和尾状功能相对于增强信息的表示和预测误差信号传导而言。 儿童躁郁症不是。 取而代之的是，儿童期躁郁症与组织额叶和顶叶皮层的组织区域的困难有关注意力控制很重要。 CD+CU的年轻人在这些能力中没有显示障碍。 重要的是，我们的经验工作将CD+CU与ADHD青年和患有躁郁症的年轻人区分开来，使我们能够进一步指定针对该疾病的CD+CU青年的神经生物学叙述。 此外，这项工作使我们能够在CD+CU中确定哪些神经区域被破坏，因此提供了可能使CD+CU青年受益的干预措施的线索。 至关重要的是，这项工作使我们能够确定可用于评估该人群治疗功效的客观生物标记。 目前，我的小组正在使用该方案中确定的fMRI生物标志物任务来研究CD+CU青年的两种治疗干预措施，以评估治疗功效。