This project has established a series of core neuro-biological findings regarding the basis of Conduct Disorder (CD). Over the past year, we have identified core neuro-computational impairments that are: (i) specific to youth with CD and high callous-unemotional (CU) traits (reduced guilt and empathy); (ii) specific to youth with CD and low callous-unemotional traits; (iii) common to youth with CD irrespective of CU trait level. In our previous work, we have shown that youth with CD and high CU traits show reduced amygdala responses to the distress of others. This year we have continued this work revealing that patients with CD+CU show reduced amygdala responses to other forms of negative stimuli. We have shown that the level of this impairment relates to the level of CU traits. In short, reduced amygdala functioning contributes to the reduced guilt and empathy in this population. In our earlier work, we concentrated less on youth with CD and low CU traits. However, over the past year, we have shown that this group shows increased amygdala responses to not only threat cues but also social provocation. Moreover, they show increased responses to threat not only within the amygdala but also the periaqueductal gray. This is important because these regions have been shown to mediate reactive aggression in work with animals. Reactive aggression is aggression shown in response to threat, social provocation and frustration. Youth with CD and low CU traits show a specifically increased risk for the display of reactive aggression. In addition, over the past year, we have begun to identify neuro-computational impairments that are common to both youth with CD+CU and CD-CU. These impairments are seen in systems involved in decision-making. Specifically, we have identified impaired functioning in ventromedial prefrontal cortex in youth with CD, irrespective of CU trait level, when participants were choosing how to respond to another individual's social provocation. Patients with CD, irrespective of CU level, failed to show modulated ventromedial prefrontal cortex functioning when choosing how to retaliate to another individual's provocation. Importantly, level of failed responding predicted level of reactive aggression shown by the patients in their communities. In addition, we have identified a specific form of dysfunction in regions involved in changing and stopping behaviors; anterior insula and dorsomedial frontal cortex. In healthy individuals, these regions are sensitive to the expected value of a behavior. They show greater activity when an individual is about to make a poor choice. Moreover, their level of activity is a function of how poor the choice is; these regions show greater activity the more an individual might lose if they make that choice. Patients with CD show reduced modulation of activity within these regions as a function of the poverty of the choice. Importantly, the level of reduced modulation of activity within these regions relates to the level of CD symptoms shown by these youth. 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.
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