Identifying novel types of irritability using a developmental genetic approach

Lucy Riglin, Olga Eyre, Ajay Thapar, Argyris Stringaris, Ellen Leibenluf, Daniel S Pine, Kate Tilling, George Davey Smith, Michael C O'Donovan, Anita Thapar

Research output: Contribution to journalArticle (Academic Journal)peer-review

30 Citations (Scopus)
74 Downloads (Pure)


ObjectiveIrritability is a common reason for referral to services, strongly associated with impairment and negative outcomes, but is a nosological and treatment challenge. A major issue is how irritability should be conceptualized. This study 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. 
MethodData were analyzed in the Avon Longitudinal Study of Parents and Children, a prospective UK population-based cohort. Irritability trajectory-classes were estimated for 7924 individuals with data at multiple time-points across childhood and adolescence (4 possible time-points from approximately ages 7 to 15 years). Psychiatricdiagnoses were assessed at approximately ages 7 and 15 years. Psychiatric genetic risk wasindexed by polygenic risk scores (PRS) for attention-deficit/hyperactivity disorder (ADHD) and depression derived using large genome-wide association study results. 
ResultsFive irritability trajectory classes were identified: low (81.2%), decreasing (5.6%), increasing (5.5%), latechildhood limited (5.2%) and high-persistent (2.4%). The early-onset, high-persistent trajectory was associated with male preponderance, childhood ADHD (OR=108.64 (57.45-204.41), p<0.001) and ADHD PRS (OR=1.31 (1.09-1.58), p=0.005); the adolescent-onset, increasing trajectory was associated with female preponderance, adolescent depression (OR=5.14 (2.47-10.73), p<0.001) and depression PRS (OR=1.20, (1.05-1.38), p=0.009). Both trajectory classeswere associated with adolescent depression diagnosis and ADHD PRS. 
ConclusionsThe developmental context of irritability may be important in its conceptualization: early-onsetpersistent irritability maybe more 'neurodevelopmental/ADHD-like’ and later-onset irritability more ‘depression/mood-like’. This has implications for treatment as well as nosology
Original languageEnglish
Pages (from-to)635-642
Number of pages8
JournalAmerican Journal of Psychiatry
Issue number8
Early online date1 Jul 2019
Publication statusE-pub ahead of print - 1 Jul 2019


  • Child Psychiatry
  • Diagnosis and Classification
  • Irritability
  • Longitudinal
  • Genetic
  • Polygenic Risk Scores


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