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 particular, we were the first to identify that youth with CD show a heightened risk for an enlarged cavum septum pellucidum (CSP). The rapid development of the alvei of limbic structures including the amygdala, hippocampus and septal nuclei in the first six months of life is attributed to fusion of the CSP. If there is disruption in the early development of these regions, the CSP may appear enlarged. As such, the observation of a significantly higher incidence of enlarged CSP in CD indicates that the condition represents, for at least some cases, an early neurodevelopmental disorder, particularly implicating the limbic system. In line with this, a second study completed this year used structural MRI to reveal that youth with CD show reduced temporal cortex, amygdala and striatal volumes. The level of reduction in temporal cortex is also related to the level 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 dysfunction being robustly observed as well as additional difficulties in dorsomedial frontal and anterior insula cortex being identified. These latter difficulties reflect a failure in the use of expected value information to guide the individual away from poor choices. Critically, this work has allowed us to identify objective bio-markers 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.

Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2013
Total Cost
$1,295,200
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
Zip Code
Wallace, Gregory L; White, Stuart F; Robustelli, Briana et al. (2014) Cortical and subcortical abnormalities in youths with conduct disorder and elevated callous-unemotional traits. J Am Acad Child Adolesc Psychiatry 53:456-65.e1
Keysers, Christian; Meffert, Harma; Gazzola, Valeria (2014) Reply: Spontaneous versus deliberate vicarious representations: different routes to empathy in psychopathy and autism. Brain 137:e273
White, Stuart F; Fowler, Katherine A; Sinclair, Stephen et al. (2014) Disrupted expected value signaling in youth with disruptive behavior disorders to environmental reinforcers. J Am Acad Child Adolesc Psychiatry 53:579-88.e9
White, Stuart F; Pope, Kayla; Sinclair, Stephen et al. (2013) Disrupted expected value and prediction error signaling in youths with disruptive behavior disorders during a passive avoidance task. Am J Psychiatry 170:315-23
White, Stuart F; Brislin, Sarah J; Meffert, Harma et al. (2013) Callous-unemotional traits modulate the neural response associated with punishing another individual during social exchange: a preliminary investigation. J Pers Disord 27:99-112
R Blair, R James (2013) Psychopathy: cognitive and neural dysfunction. Dialogues Clin Neurosci 15:181-90
Coker-Appiah, Dionne S; White, Stuart F; Clanton, Roberta et al. (2013) Looming animate and inanimate threats: the response of the amygdala and periaqueductal gray. Soc Neurosci 8:621-30
Blair, R J R; Mitchell, D G V (2009) Psychopathy, attention and emotion. Psychol Med 39:543-55
Marsh, Abigail A; Finger, Elizabeth C; Mitchell, Derek G V et al. (2008) Reduced amygdala response to fearful expressions in children and adolescents with callous-unemotional traits and disruptive behavior disorders. Am J Psychiatry 165:712-20
Marsh, Abigail A; Blair, R J R (2008) Deficits in facial affect recognition among antisocial populations: a meta-analysis. Neurosci Biobehav Rev 32:454-65

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