Harriet Cornwell

RESEARCH OUTPUT

Selected publications

1. Dimensional Associations Between Conduct Problems and Brain Structure Across 18 International Cohorts in ENIGMA.Journal of the American Academy of Child and Adolescent Psychiatry · 2026
   OBJECTIVE: Although conduct problems (CPs) are continuously distributed, little is known about how dimensional measures of CPs map onto brain structure. Therefore a large sample was used to comprehensively assess associations between dimensionally measured CPs and brain structure. METHOD: T1-weighted structural brain magnetic resonance imaging scans from 14,160 youths (5-21 years old, 46.2% female) across 18 international case-control, community-based, and population-based cohorts were preprocessed using ENIGMA-standardized protocols. Regression models examined associations between CPs and cortical thickness, surface area, and subcortical volumes, adjusting for age, sex, and intracranial volume. Moderation by sex, age, and callous-unemotional traits was also investigated. RESULTS: Widespread but small (β = -0.02 to -0.07) negative associations were observed between CPs and surface area (total surface area, 23/34 regions), cortical thickness (average thickness, 15/34 regions), and amygdalar and hippocampal volumes. Sex was a key moderator, with many surface area associations limited to boys and some thickness associations limited to girls. Some associations were stronger in younger children and at lower levels of callous-unemotional traits. The impact of adjusting for IQ and other psychopathology varied by outcome (eg, most surface area findings survived IQ adjustment, whereas cortical thickness associations did not). CONCLUSION: CPs were associated with subtle, yet widespread, alterations in brain structure. Findings overlapped with differences observed in categorically measured conduct disorder, but novel associations with cortical thickness were identified. This provides further evidence that neuroanatomical differences are not limited to youth with clinically elevated CPs. Our findings have potential implications for neurocognitive models of CPs as they extend beyond the regions highlighted in these models. STUDY REGISTRATION INFORMATION: Investigating dimensional relationships between conduct problems and brain structure: an ENIGMA mega-analysis; https://osf.io/nzj3r/.

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2. Brain Age in Conduct Disorder:: A Mega-Analysis of the ENIGMA Antisocial Behavior Working Group.bioRxiv : the preprint server for biology · 2026
   Conduct disorder (CD) is the leading global cause of mental health burden in children and adolescents and has recently been hypothesized to be a neurodevelopmental disorder. Although prior research has identified neuroanatomical differences associated with CD, it remains unclear whether these differences reflect atypical brain development. Here, we investigated the difference between an individual's brain age and chronological age as a proxy for variations in brain maturation. Using a pretrained model, we estimated brain age from structural neuroimaging data obtained from 1,119 youth with CD and 1,183 typically developing controls across 14 international cohorts participating in the ENIGMA-Antisocial Behavior Working Group. Youth with CD exhibited a statistically robust but small acceleration in brain age compared to typically developing youth (around 0.50 years), which was restricted to the adolescence-onset subtype of the disorder. Our large-scale, coordinated analysis provides the first evidence of accelerated neurodevelopment as a potential mechanism underlying CD.

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3. Brain Responses During Face Processing in Conduct Disorder: Considering Sex and Callous-Unemotional Traits.Biological psychiatry · 2025
   BACKGROUND: Functional magnetic resonance imaging studies of conduct disorder (CD) have mostly been limited to males. Here, we examined whether male and female youths with CD showed similar or distinct alterations in brain responses to emotional faces, using a large sample of male and female youths with CD. We also investigated the influence of callous-unemotional (CU) traits. METHODS: Brain responses to angry, fearful, and neutral faces were assessed in 161 youths with CD (74 female) and 241 typically developing (TD) youths (139 female) ages 9 to 18 years. Categorical analyses tested for diagnosis effects (CD vs. TD and CD with high levels of CU traits [CD/HCU] vs. low levels of CU traits [CD/LCU] vs. TD) and sex × diagnosis interactions. RESULTS: When processing faces in general (all faces vs. baseline), youths with CD exhibited lower amygdala responses compared with TD youths, which seemed to be driven by the CD/HCU subgroup. Sex × CU subgroup interactions were identified in the amygdala (CD/LCU females TD males) and anterior insula (CD/HCU females > CD/LCU females; CD/HCU males < CD/LCU males). CONCLUSIONS: The findings for males support an influential neurocognitive model of CD. However, the association between CU traits and brain response to facial expressions differed in females and males with CD, suggesting distinct pathophysiological processes.

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4. Neural activation during processing of emotional faces as a function of resilience in adolescents.European child & adolescent psychiatry · 2025
   Neuroimaging studies suggest that resilience to adversity is linked to reduced emotional reactivity or enhanced emotion regulation. However, such studies are scarce and mainly use adult samples and categorical definitions of resilience. Using a novel, data-driven approach to define resilience dimensionally, based on cumulative adversity exposure across childhood and psychopathology, we investigated associations between resilience and brain activation during facial emotion processing in youth. We also tested for sex differences in the relationship between resilience and brain activation. fMRI data were acquired from 208 youths (aged 9-18 years; Mean age = 13.28), while viewing angry, fearful, and neutral faces. Whole-brain analyses were performed, followed by region-of-interest analyses focusing on the amygdala, hippocampus, and prefrontal cortex. Resilience was positively correlated with bilateral inferior frontal gyrus responses to fearful (versus neutral) faces, and negatively correlated with right superior temporal gyrus, left hippocampal, and right inferior frontal gyrus responses to neutral faces (versus fixation). Sex-by-resilience interactions were observed in the medial prefrontal cortex: males showed positive, while females showed negative, associations between resilience and brain activation, though these results did not survive correction for multiple comparisons. These findings provide further evidence that resilience in youth is associated with enhanced emotion regulation at a neural level.

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