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Identifying novel types of irritability using a developmental genetic approach

Riglin, Lucy, Eyre, Olga, Thapar, Ajay K., Stringaris, Argyris, Leibenluft, Ellen, Pine, Daniel S., Tilling, Kate, Davey Smith, George, O'Donovan, Michael C. and Thapar, Anita 2019. Identifying novel types of irritability using a developmental genetic approach. American Journal of Psychiatry 176 (8) , pp. 635-642. 10.1176/appi.ajp.2019.18101134

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Objective: Irritability, which is strongly associated with impairment and negative outcomes, is a common reason for referral to mental health services but is a nosological and treatment challenge. A major issue is how irritability should be conceptualized. The authors used a developmental approach to test the hypothesis that there are several forms of irritability, including a “neurodevelopmental/ADHD-like” type, with onset in childhood, and a “depression/mood” type, with onset in adolescence. Methods: Data were analyzed from the Avon Longitudinal Study of Parents and Children, a prospective U.K. population-based cohort. Irritability trajectory classes were estimated for 7,924 individuals with data at multiple time points across childhood and adolescence (four possible time points from approximately ages 7 to 15). Psychiatric diagnoses were assessed at approximately ages 7 and 15. Psychiatric genetic risk was indexed by polygenic risk scores (PRSs) for attention deficit hyperactivity disorder (ADHD) and depression, derived using large genome-wide association study results. Results: Five irritability trajectory classes were identified: low (81.2%), decreasing (5.6%), increasing (5.5%), late-childhood limited (5.2%), and high-persistent (2.4%). The early-onset high-persistent trajectory was associated with male preponderance, childhood ADHD (odds ratio=108.64, 95% CI=57.45–204.41), and ADHD PRS (odds ratio=1.31, 95% CI=1.09–1.58). The adolescent-onset increasing trajectory was associated with female preponderance, adolescent depression (odds ratio=5.14, 95% CI=2.47–10.73), and depression PRS (odds ratio=1.20, 95% CI=1.05–1.38). Both the early-onset high-persistent and adolescent-onset increasing trajectory classes were associated with adolescent depression diagnosis and ADHD PRS. Conclusions: The developmental context of irritability may be important in its conceptualization: early-onset persistent irritability may be more neurodevelopmental/ADHD-like and later-onset irritability more depression/mood-like. These findings have implications for treatment as well as nosology.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: American Psychiatric Publishing
ISSN: 0002-953X
Date of First Compliant Deposit: 16 April 2019
Date of Acceptance: 8 April 2019
Last Modified: 24 Feb 2022 17:32

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