Emotional dysfunction and childhood behavioral disturbance

这个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，特别是具有冷酷无情(CU)特征(减少内疚和同理心)的CD。一年来，我们取得的主要成就有： 首先，在一系列研究中，我们使用结构成像研究来确定是否有可能识别具有和不具有CU特征的CD的结构解剖标记。在过去的一年里，我们扩展了我们之前的发现，证明了患有CD的年轻人显示出颞叶上皮质皮质厚度减少，并有迹象表明额叶腹内侧皮层回缩减少。这在患有CD的年轻人中尤其明显，他们没有共同患有注意力缺陷/多动障碍。皮质表面积无组间差异。然而，患有CD的年轻人也表现出杏仁核和纹状体(壳核和苍白球)体积减少。右侧颞叶皮质厚度与CU特征的严重程度呈显著负相关。 其次，在这一方案的早期工作中，我们证明了Cd+CU与基于奖惩的决策受损有关，这种损害与眼眶额叶皮质和尾状核内的功能障碍有关。这与预测误差信号(表明结果比个人预期的更好或更差)、学习的关键信号和期望值(代表行动执行后可能获得的奖励或惩罚)中的计算障碍有关。这一观点在今年的其他决策研究中得到了证实和推广，尾状核、背内侧前额叶皮质和前脑岛皮质功能障碍在一个利用环境强化的范例中被复制。在这一范式中，在使用期望值信息来引导个体远离不良选择方面的失败再次在患有CD的青年中被观察到。有趣的是，这一失败似乎与患有CD+CU的年轻人没有特别的关系。进一步查明DBD共有的具体缺陷以及CD+CU和CD-CU特有的缺陷将是工作组今后工作的重点。 关键的是，这项工作使我们能够确定客观的生物标记物，这些生物标记物可以用于正在进行的工作，以评估这一人群的治疗效果。事实上，我们的小组在其他方案中，即将开始使用在该方案下开发的范例来检查治疗效果。

This project has established a series of core neuro-biological findings regarding the basis of Conduct Disorder (CD), particularly CD with Callous-Unemotional (CU) traits (reduced guilt and empathy). Over the past year, our main achievements have been the following: First, in a series of studies we have used structural imaging studies to identify whether it is possible to identify structural anatomical markers of CD with and without CU traits. In the past year we have extended our previous findings by demonstrating that youths with CD showed reduced cortical thickness in the superior temporal cortex and had indications of reduced gyrification in the ventromedial frontal cortex. This was particularly pronounced for youths with CD without comorbid attention-deficit/hyperactivity disorder. There were no group differences in cortical surface area. However, youths with CD also showed reduced amygdala and striatum (putamen and pallidum) volumes. Right temporal cortical thickness was significantly inversely related to severity of CU traits. Second, in earlier work on this protocol, we demonstrated that CD+CU is associated with impaired reward/punishment based decision making and this impairment is related to dysfunction within orbital frontal cortex and caudate. This relates to computational impairments in prediction error signaling (signaling that an outcome is better or worse than the individual expected it to be), a critical signal for learning and expected value (representing the likely reward or punishment that will be received following performance of the action). This view has been confirmed and extended in additional studies of decision making this year with the caudate, dorsomedial prefrontal cortex and anterior insula cortex dysfunction being replicated in a paradigm utilizing environmental reinforcement. In this paradigm failure in the use of expected value information to guide the individual away from poor choices was again observed in youth with CD. Interestingly, this failure does not seem to be specifically related to youth with CD+CU. Further identifying specific deficits common to DBD and specific to CD+CU and CD-CU will be a focus of the group moving forward. Critically, this work has allowed us to identify objective biomarkers that can be used in on-going work to assess treatment efficacy in this population. Indeed, our group, in other protocols, is about to start examining treatment efficacy using the paradigms developed under this protocol.