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.

该项目建立了一系列关于行为障碍（CD）基础的核心神经生物学发现，特别是具有冷酷无情特征（减少内疚和同理心）的行为障碍；光盘+CU： (i) CD+CU 与处理他人恐惧的受损有关，并且这种受损与杏仁核对这些表达的反应减弱有关。 这种损伤是恐惧表情所特有的，而愤怒表情则不会出现这种损伤。 这些数据使我们能够了解这种疾病患者共情缺陷的基础。 (ii) CD+CU 与决策受损有关，这种损害与腹内侧前额叶皮层内强化信息表示的破坏（该行为导致奖励/惩罚的可能性有多大）有关。 这些数据使我们能够了解这种疾病患者决策障碍的基础。 (iii) 患有注意力缺陷多动障碍 (ADHD) 但没有 CD 的患者在杏仁核对恐惧表达的反应或腹内侧前额叶皮质内的强化信息信号传导方面没有表现出任何困难。这很重要，因为 CD 和 ADHD 经常出现在同一个青少年身上。大约 65% 患有 CD+CU 的青少年也符合 ADHD 的标准。然而，通过证明患有 ADHD 但没有 CD 的青少年在恐惧表达或强化处理方面没有表现出任何问题，我们可以确定这些困难与 CD+CU 而不是与共病 ADHD 有关。 在最近完成或目前正在进行的研究中，我们扩展了我们早期的工作，表明： (i) CD+CU 中的同理心缺陷延伸到对另一个人的痛苦的反应。 这些缺陷也与杏仁核对其他人疼痛的反应减少有关。 （ii）决策障碍不仅与腹内侧前额叶皮层内强化信息表示的缺陷有关，而且还与腹内侧前额叶皮层和尾状核内预测误差信号的缺陷有关。 当个人意外地收到奖励或惩罚时，大脑中就会发出预测错误信号。 这种信号很重要，因为它可以促使人们快速了解引发这种强化的行为与强化本身之间的关联。 不良的预测错误信号意味着较差的情绪学习，从而导致较差的决策。 (iii) 与 Leibenluft 博士合作，我们发现，虽然患有 CD+CU 和儿童双相情感障碍的青少年在决策障碍方面表现出一些相似的行为，但这些障碍的神经基础却明显不同。 CD+CU 与腹内侧前额叶皮层和尾状核在强化信息表示和预测误差信号方面的功能困难有关。 儿童躁郁症则不然。 相反，儿童双相情感障碍与组织对注意力控制很重要的额叶和顶叶皮层区域的困难有关。 患有 CD+CU 的青少年在这些能力上没有表现出任何损害。 重要的是，我们将患有 CD+CU 的青少年与患有 ADHD 的青少年和患有双相情感障碍的青少年区分开来的实证工作使我们能够进一步明确针对这种疾病特有的针对患有 CD+CU 的青少年的神经生物学解释。 此外，这项工作使我们能够确定 CD+CU 中哪些神经区域受到破坏，从而为可能使 CD+CU 青少年受益的干预措施提供线索。 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效果的客观生物标志物。 目前，我的小组正在制定协议，使用该协议中确定的功能磁共振成像生物标志物任务来调查 CD+CU 青少年的两种治疗干预措施，以评估治疗效果。