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

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Main Authors: Amy Shakeshaft, Luis C. Farhat, Charlotte A. Dennison, Olga Eyre, Olakunle Oginni, Michael C. O'Donovan, Argyris Stringaris, Ellen Leibenluft, Guilherme V. Polanczyk, Lucy Riglin, Anita Thapar
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Published: Wiley 2025
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author Amy Shakeshaft
Luis C. Farhat
Charlotte A. Dennison
Olga Eyre
Olakunle Oginni
Michael C. O'Donovan
Argyris Stringaris
Ellen Leibenluft
Guilherme V. Polanczyk
Lucy Riglin
Anita Thapar
author_facet Amy Shakeshaft
Luis C. Farhat
Charlotte A. Dennison
Olga Eyre
Olakunle Oginni
Michael C. O'Donovan
Argyris Stringaris
Ellen Leibenluft
Guilherme V. Polanczyk
Lucy Riglin
Anita Thapar
Amy Shakeshaft
Luis C. Farhat
Charlotte A. Dennison
Olga Eyre
Olakunle Oginni
Michael C. O'Donovan
Argyris Stringaris
Ellen Leibenluft
Guilherme V. Polanczyk
Lucy Riglin
Anita Thapar
collection Wiley Open Access
contents Mapping phenotypic and genetic relationships among irritability, depression and ADHD in adolescence using network analysis Amy Shakeshaft Luis C. Farhat Charlotte A. Dennison Olga Eyre Olakunle Oginni Michael C. O'Donovan Argyris Stringaris Ellen Leibenluft Guilherme V. Polanczyk Lucy Riglin Anita Thapar Journal of Child Psychology and Psychiatry 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 behavioural problems. 10.1111/jcpp.70040 http://creativecommons.org/licenses/by/4.0/
doi_str_mv 10.1111/jcpp.70040
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spellingShingle Mapping phenotypic and genetic relationships among irritability, depression and ADHD in adolescence using network analysis
Amy Shakeshaft
Luis C. Farhat
Charlotte A. Dennison
Olga Eyre
Olakunle Oginni
Michael C. O'Donovan
Argyris Stringaris
Ellen Leibenluft
Guilherme V. Polanczyk
Lucy Riglin
Anita Thapar
Journal of Child Psychology and Psychiatry
Mapping phenotypic and genetic relationships among irritability, depression and ADHD in adolescence using network analysis Amy Shakeshaft Luis C. Farhat Charlotte A. Dennison Olga Eyre Olakunle Oginni Michael C. O'Donovan Argyris Stringaris Ellen Leibenluft Guilherme V. Polanczyk Lucy Riglin Anita Thapar Journal of Child Psychology and Psychiatry 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 behavioural problems. 10.1111/jcpp.70040 http://creativecommons.org/licenses/by/4.0/
title Mapping phenotypic and genetic relationships among irritability, depression and ADHD in adolescence using network analysis
topic Journal of Child Psychology and Psychiatry
url https://acamh.onlinelibrary.wiley.com/doi/10.1111/jcpp.70040