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Identifying novel types of irritability using a developmental genetic approach

Riglin, Lucy, Eyre, Olga, Thapar, Ajay K. ORCID:, Stringaris, Argyris, Leibenluft, Ellen, Pine, Daniel S., Tilling, Kate, Davey Smith, George, O'Donovan, Michael C. ORCID: and Thapar, Anita ORCID: 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: 10 Nov 2023 18:59

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