Emotional dysfunction and childhood behavioral disturbance

该项目已经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CD与无情的特征（减少内疚和同情）; CD+CU： （一） CD+CU与对他人的恐惧的受损处理有关，这种受损与杏仁核对这些表达的反应降低有关。 这种损害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共情缺陷的基础。 （二） CD+CU与决策能力受损有关，这种损害与腹内侧前额叶皮层内强化信息（行为导致奖励/惩罚的可能性）的表达中断有关。 这些数据使我们能够了解这种疾病患者决策障碍的基础。 （三） 注意缺陷多动障碍（ADHD）但没有CD的患者在杏仁核对恐惧表情的反应或腹内侧前额叶皮层内强化信息的信号传导方面没有表现出任何困难。这一点很重要，因为CD和ADHD经常出现在同一个年轻人身上。大约65%的CD+CU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问题，我们可以肯定这些困难与CD+CU有关，而不是共病ADHD。 在最近完成或正在进行的研究中，我们通过显示以下内容扩展了我们早期的工作： （一） CD+CU的共情缺陷扩展到对另一个人疼痛的反应。 这些缺陷也与杏仁核对另一个人疼痛的反应减少有关。 （二） 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，而且与腹内侧额叶皮层和尾状核内预测错误信号的缺陷有关。 当个体意外地收到奖励或惩罚时，大脑中就会出现预测错误信号。 这种信号很重要，因为它促使人们快速学习引发这种强化的行为与强化本身之间的关联。 预测错误信号差意味着情绪学习差，从而导致决策能力差。 （三） 在与Leibenluft博士的合作中，我们已经表明，虽然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之处，但这些障碍的神经基础明显不同。 CD+CU与腹内侧前额叶皮层和尾状核功能在强化信息和预测错误信号的表示方面的困难有关。 儿童期躁郁症则不然。 相反，儿童双相情感障碍与组织对注意力控制重要的外侧额叶和顶叶皮质区域的困难有关。 患有CD+CU的青少年在这些能力方面没有表现出损害。 重要的是，我们的经验工作区分青少年与CD+CU与青少年多动症和青少年双相情感障碍，使我们能够进一步指定一个神经生物学帐户的青少年与CD+CU是特定于这种疾病。 此外，这项工作使我们能够确定哪些神经区域在CD+CU中被破坏，从而为可能使CD+CU青少年受益的干预措施提供线索。 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，我的小组正在开发方案，使用本方案中确定的fMRI生物标志物任务来评估CD+CU青年患者的两种治疗干预措施，以评估治疗效果。

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.