Callous-unemotional traits drive reduced white-matter integrity in youths with conduct problems.

BACKGROUND: Callous-unemotional (CU) traits represent a significant risk factor for severe and persistent conduct problems in children and adolescents. Extensive neuroimaging research links CU traits to structural and functional abnormalities in the amygdala and ventromedial prefrontal cortex. In addition, adults with psychopathy (a disorder for which CU traits are a developmental precursor) exhibit reduced integrity in uncinate fasciculus, a white-matter (WM) tract that connects prefrontal and temporal regions. However, research in adolescents has not yet yielded similarly consistent findings. METHOD: We simultaneously modeled CU traits and externalizing behaviors as continuous traits, while controlling for age and IQ, in order to identify the unique relationship of each variable with WM microstructural integrity, assessed using diffusion tensor imaging. We used tract-based spatial statistics to evaluate fractional anisotropy, an index of WM integrity, in uncinate fasciculus and stria terminalis in 47 youths aged 10-17 years, of whom 26 exhibited conduct problems and varying levels of CU traits. RESULTS: Whereas both CU traits and externalizing behaviors were negatively correlated with WM integrity in bilateral uncinate fasciculus and stria terminalis/fornix, simultaneously modeling both variables revealed that these effects were driven by CU traits; the severity of externalizing behavior was not related to WM integrity after controlling for CU traits. CONCLUSIONS: These results indicate that WM abnormalities similar to those observed in adult populations with psychopathy may emerge in late childhood or early adolescence, and may be critical to understanding the social and affective deficits observed in this population.

The role of 5-HTTLPR in choosing the lesser of two evils, the better of two goods: examining the impact of 5-HTTLPR genotype and tryptophan depletion in object choice.

RATIONALE: The serotonin (5-HT) system is considered important for decision-making. However, its role in reward- and punishment-based processing has not yet been clearly determined. OBJECTIVES: The present study examines the effect of 5-HTTLPR genotype and tryptophan depletion on reward- and punishment-related processing, using a task that considers decision-making in situations of subtlety of choice. Thus, it considers that response choice often occurs in situations where both options are desirable (e.g., choosing between mousse au chocolat or crème caramel cheesecake from a menu) or undesirable. It also considers that response choice is easier when the reinforcements associated with the options are far apart, rather than close, in value. MATERIALS AND METHODS: Healthy volunteers underwent acute tryptophan depletion (ATD) or control procedures and genotyping of the 5-HTTLPR for long and short allele variants. We then examined the effects and interactions of ATD and the serotonin promoter polymorphism genotype on two aspects of decision-making: (a) decision form, choosing between two objects to gain the greater reward or lesser punishment and (b) between-object reinforcement distance, the difference in reinforcements associated with two options. RESULTS: ATD and LL homozygosity had comparable interactions with decision form and between-object reinforcement distance. Specifically, both modulated the effect of between-object reinforcement distance when deciding between objects both associated with punishment. Moreover, ATD and genotype interacted with ATD disproportionately affecting the performance of the LL homozygous group. CONCLUSIONS: These results suggest that serotonin is particularly associated with punishment, rather than reward-related processing, and that individual sensitivity to punishment-related information and tryptophan depletion varies with genotype.

Neural correlates of response reversal: considering acquisition.

Previous work on response reversal has typically used a single pair of stimuli that serially reverse. This conflation of acquisition and reversal processes has prevented an examination of the functional role of neural systems implicated in response reversal during acquisition despite the relevance of such data in evaluating accounts of response reversal. In the current study, participants encountered 16 independent reversing stimulus pairs in the context of a probabilistic response reversal paradigm. Functional regions of interest identified as involved in response reversal through a contrast used in the previous literature (punished errors made in the reversal phase versus rewarded correct responses), were interrogated across conditions. Consistent with suggestions that middle frontal cortex codes reward, this region showed significantly greater responses to rewarded rather than punished trials irrespective of accuracy or learning phase (acquisition or reversal). Consistent with the suggestion that this coding of the expectation of reinforcement is acquired via input from the amygdala, we observed significant positive connectivity between activity within the amygdala and a region of rostral anterior cingulate cortex highly proximal to this region of middle frontal/mesial prefrontal cortex. In contrast, inferior frontal cortex, anterior cingulate cortex and caudate showed greater responses to punished errors than to the rewarded correct responses. These three regions also showed significant activation to rewarded errors during acquisition, in contrast to positions suggesting that inferior frontal cortex represents punishment or suppresses previously rewarded responses. Moreover, a connectivity analysis with an anterior cingulate cortex seed revealed highly significant positive connectivity among them. The implications of these data for recent accounts of response reversal and of response reversal impairments in specific neuropsychiatric populations are discussed.