Evidence map›Paper›PMID 40974183›Full record

ArticleJournal of child psychology and psychiatry, and allied disciplines2026

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 and 1 more

Abstract read
In one paragraph

Article in Journal of child psychology and psychiatry, and allied disciplines, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

11 authors.

Amy ShakeshaftDivision of Psychological Medicine and Clinical Neurosciences, Wolfson Centre for Young People's Mental Health, Cardiff University, Cardiff, UK.ORCID 0000-0003-1412-5413
Luis C FarhatDepartment of Psychiatry, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil.ORCID 0000-0002-3147-8344
Charlotte A DennisonDivision of Psychological Medicine and Clinical Neurosciences, Wolfson Centre for Young People's Mental Health, Cardiff University, Cardiff, UK.ORCID 0000-0002-7493-2041
Olga EyreDivision of Psychological Medicine and Clinical Neurosciences, Wolfson Centre for Young People's Mental Health, Cardiff University, Cardiff, UK.ORCID 0000-0003-1944-9679
Olakunle OginniDivision of Psychological Medicine and Clinical Neurosciences, Wolfson Centre for Young People's Mental Health, Cardiff University, Cardiff, UK.
Michael C O'DonovanDivision of Psychological Medicine and Clinical Neurosciences, Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
Argyris StringarisFaculty of Brain Sciences, Division of Psychiatry, University College London, London, UK.
Ellen LeibenluftOffice of the Scientific Director, National Institute of Mental Health, Bethesda, MD, USA.
Guilherme V PolanczykDepartment of Psychiatry, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil.
Lucy RiglinDivision of Psychological Medicine and Clinical Neurosciences, Wolfson Centre for Young People's Mental Health, Cardiff University, Cardiff, UK.ORCID 0000-0002-5124-5230
Anita ThaparDivision of Psychological Medicine and Clinical Neurosciences, Wolfson Centre for Young People's Mental Health, Cardiff University, Cardiff, UK.

Funding

The Pathophysiology and Treatment Of Children With Severe Mood DysregulationZIAMH002786 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI LEIBENLUFT, ELLEN · 2009 to 2023
$34.0M
Intramural NIH HHS ZIA MH002786Medical Research Council MR/X021769/1NIMH NIH HHS ZIAMH002786Wellcome TrustWolfson Foundation
6 · The paper itself

Abstract

backgroundIrritability 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.

methodsWe 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).

resultsResults 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.

conclusionsAlthough 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.

Indexed as

Attention Deficit Disorder with HyperactivityDepressionDepressive DisorderIrritable MoodAdolescentFemaleHumansLongitudinal StudiesMaleMultifactorial InheritancePhenotypeADHDALSPACcomorbiditydepressiongeneticsIrritabilityoppositional defiant disorder

Identifiers

PMID40974183
PMCPMC12883585

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.