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Mapping phenotypic and genetic relationships among irritability, depression and ADHD in adolescence using network analysis

Title: Mapping phenotypic and genetic relationships among irritability, depression and ADHD in adolescence using network analysis
Authors: Shakeshaft, Amy; Farhat, Luis C.; Dennison, Charlotte A.; Eyre, Olga; Oginni, Olakunle; O'Donovan, Michael C.; Stringaris, Argyris; Leibenluft, Ellen; Polanczyk, Guilherme V.; Riglin, Lucy; Thapar, Anita
Publisher Information: Wiley
Publication Year: 2026
Collection: Cardiff University: ORCA (Online Research @ Cardiff)
Description: Background Irritability is a common reason for referral to child and adolescent mental health services. However, debate exists as to whether irritability is best conceptualised and treated as a feature of mood disorder, oppositional defiant disorder or a core symptom of ADHD. Methods We use network analyses to examine the relationships between adolescent irritability, headstrong/hurtful ODD items, depression and ADHD phenotypes, and polygenic scores (PGS) for depression and ADHD using the Avon Longitudinal Study of Parents and Children (ALSPAC). In primary analysis, irritability, depression, headstrong/hurtful ODD items and ADHD were defined using the Development and Well-Being Assessment (DAWBA) at age 15. In secondary analysis, phenotypes were defined using the Short Mood and Feelings Questionnaire (SMFQ) and the Strengths and Difficulties Questionnaire (SDQ) ADHD and behavioural subscales at age 13. Finally, we tested for network replicability using confirmatory network analysis in the Millennium Cohort Study (MCS). Results Results of network analyses using the DAWBA in ALSPAC indicated irritability was most strongly associated with headstrong/hurtful ODD items, followed by ADHD and depression. When including PGS, we observed an edge between irritability and depression PGS but not between irritability and ADHD PGS. Irritability appeared to be the primary pathway between ADHD and depression as well as between headstrong/hurtful ODD items and depression. Results were similar using SMFQ/SDQ in ALSPAC and confirmatory network analysis indicated excellent model fit in MCS. Conclusions Although irritability appears to be transdiagnostic, phenotypically, it was most strongly associated with headstrong/hurtful ODD items and broader behavioural problems, which favours the ICD-11 approach of including irritability as a specifier of ODD. However, irritability appeared to be a key connector between both ADHD and behavioural problems to depression; thus, is important to monitor and treat in affected youth with ADHD or ...
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
Relation: https://orca.cardiff.ac.uk/id/eprint/181255/1/Child%20Psychology%20Psychiatry%20-%202025%20-%20Shakeshaft%20-%20Mapping%20phenotypic%20and%20genetic%20relationships%20among%20irritability%20%281%29.pdf; Shakeshaft, Amy https://orca.cardiff.ac.uk/view/cardiffauthors/A2665996U.html orcid:0000-0003-1412-5413 orcid:0000-0003-1412-5413, Farhat, Luis C., Dennison, Charlotte A. https://orca.cardiff.ac.uk/view/cardiffauthors/A2339759H.html orcid:0000-0002-7493-2041 orcid:0000-0002-7493-2041, Eyre, Olga https://orca.cardiff.ac.uk/view/cardiffauthors/A1443455.html, Oginni, Olakunle https://orca.cardiff.ac.uk/view/cardiffauthors/A2867173A.html, O'Donovan, Michael C. https://orca.cardiff.ac.uk/view/cardiffauthors/A038895E.html orcid:0000-0001-7073-2379 orcid:0000-0001-7073-2379, Stringaris, Argyris, Leibenluft, Ellen, Polanczyk, Guilherme V., Riglin, Lucy https://orca.cardiff.ac.uk/view/cardiffauthors/A21778658.html and Thapar, Anita https://orca.cardiff.ac.uk/view/cardiffauthors/A046713L.html orcid:0000-0002-3689-737X orcid:0000-0002-3689-737X 2026. Mapping phenotypic and genetic relationships among irritability, depression and ADHD in adolescence using network analysis. Journal of Child Psychology and Psychiatry 67 (3) , pp. 333-343. 10.1111/jcpp.70040 https://doi.org/10.1111/jcpp.70040 file https://orca.cardiff.ac.uk/id/eprint/181255/1/Child%20Psychology%20Psychiatry%20-%202025%20-%20Shakeshaft%20-%20Mapping%20phenotypic%20and%20genetic%20relationships%20among%20irritability%20%281%29.pdf
DOI: 10.1111/jcpp.70040
Availability: https://orca.cardiff.ac.uk/id/eprint/181255/; https://doi.org/10.1111/jcpp.70040
Rights: cc_by_4_0
Accession Number: edsbas.3239362A
Database: BASE