Cross-sectional and longitudinal associations of anxiety and irritability with adolescents' neural responses to cognitive conflict

Elise M Cardinale, Jessica Bezek, Santiago Morales, Courtney Filippi, Ashley R Smith, Simone Haller, Emilio A Valadez, Anita Harrewijn, Dominique Phillips, Andrea Chronis-Tuscano, Melissa A Brotman, Nathan A Fox, Daniel S Pine, Ellen Leibenluft, Katharina Kircanski

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)


BACKGROUND: Psychiatric symptoms are commonly comorbid in childhood. The ability to disentangle unique and shared correlates of comorbid symptoms facilitates personalized medicine. Cognitive control is implicated broadly in psychopathology, including in pediatric disorders characterized by anxiety and irritability. To disentangle cognitive control correlates of anxiety versus irritability, the current study leverages both cross-sectional and longitudinal data from early childhood into adolescence.

METHODS: 89 participants were recruited from a large longitudinal research study on early life temperament. The current study investigated associations of developmental trajectories of anxiety and irritability symptoms (from ages 2 to 15), as well as associations of anxiety and irritability symptoms measured cross-sectionally at age-15, with neural substrates of conflict and error processing assessed at age-15 using the Flanker Task.

RESULTS: Results of whole-brain multivariate linear models revealed that age-15 anxiety was uniquely associated with decreased neural response to conflict, across multiple regions implicated in attentional control and conflict adaptation. Conversely, age-15 irritability was uniquely associated with increased neural response to conflict in regions implicated in response inhibition. Developmental trajectories of anxiety and irritability interacted in relation to neural responses to both error and conflict.

CONCLUSIONS: Our findings suggest that neural correlates of conflict processing may relate uniquely to anxiety and irritability. Continued cross-symptom research on the neural correlates of cognitive control could stimulate advances in individualized treatment for anxiety and irritability during child and adolescent development.

Original languageEnglish
JournalBiological Psychiatry-Cognitive Neuroscience and Neuroimaging
Publication statusE-pub ahead of print - 28 Mar 2022
Externally publishedYes

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Copyright © 2022. Published by Elsevier Inc.


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