AbstractConduct problems (CP), characterised by a persistent pattern of antisocial behaviour (ASB), are the most common psychiatric condition in children and represent a significant individual, social and economic burden. The underlying cause(s) for CP is complex but there is evidence that children with CP have differences in brain anatomy and function, particularly in brain regions associated with the limbic system (i.e. the amygdala and its white matter connections, such as the uncinate fasciculus (UF)).
Currently, the main treatment available for CP are group parenting programmes, and evidence suggests that these treatments can successfully mitigate ASB in children. However, nobody has examined whether these behavioural changes are associated with brain changes. Reports have suggested, however, that up to 50% of children do not respond to such interventions. Therefore, there is currently an unmet need to identify alternative treatments for those who are unresponsive to current psychological treatment strategies. One candidate system to direct potential treatment strategies in children with persistent CP, is the oxytocin system.
The first part of this thesis (‘Study 1’) primarily aimed to investigate whether structural and functional brain impairments in CP children are ‘fixed’ or if, following a parenting intervention, they could ‘normalise’ in parallel to antisocial behaviour (ASB) improving. Chapters 3 and 4 used functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) tractography, to examine if a reduction in ASB, following a parenting intervention would be: i) associated with changes in amygdala activity in response to an emotion processing task and ii) associated with altered microstructural integrity in the uncinate fasciculus (UF). The findings from Chapter 3 showed no evidence that amygdala hypoactivity to fear ‘normalised’ in CP boys, following a reduction in ASB. However, it was established that amygdala hypoactivity to fear was only observed in CP boys with ASB that persisted following the parenting intervention and was absent in CP boys with ASB that improved. In contrast, the findings from Chapter 4 indicated that white matter abnormalities in the UF of CP boys may be ‘reversible’ following intervention, and further, these microstructural changes appeared to be associated with clinical improvement in callous-unemotional (CU) traits. In Chapter 5, the UF tract was further fractionated into three subcomponents (i.e., each terminating in different brain regions), to explore if the findings reported in Chapter 4 mapped on to changes in specific UF branches. Results suggested that the UF abnormalities which decreased in CP boys following the parenting intervention were widespread and did not map on to a specific UF subcomponent. Chapter 6 aimed to explore the microstructural properties of the ventral amygdalofugal pathway (VAF) – a recently identified white matter tract connecting brain regions understood to be important to CPs, and to understand the relevance of this tract in this cohort. Findings presented in this exploratory study implied that this tract is not impaired in CP youth.
The second part of this thesis (‘Study 2’) further explored whether functional brain abnormalities in children with persistent CP, (i.e., those who do not respond to the parenting intervention in ‘Study 1’), could ‘shift’ following a single dose of intranasal oxytocin (IN-OXT) compared to placebo. The results from Chapter 7 provided evidence that IN-OXT can modulate neural processing in treatment-resistant CP boys in the posterior cingulate cortex (PCC) / precuneus in response to viewing happy faces. These findings tentatively suggest that IN-OXT may promote a more neurotypical profile in treatment-resistant CP children.
Taken together, the work presented in this thesis has enhanced our understanding of the neural mechanisms underlying treatment response and persistence in children with earlyonset CP and provides potential implications for current clinical settings as well as future research.
|Date of Award||1 Mar 2023|
|Supervisor||Michael Craig (Supervisor) & Marija-Magdalena Petrinovic (Supervisor)|