Rxivist logo

Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 62,198 bioRxiv papers from 276,130 authors.

Identifying novel subtypes of irritability using a developmental genetic approach

By Lucy Riglin, Olga Eyre, Ajay K Thapar, Argyris Stringaris, Ellen Leibenluft, Daniel Pine, Kate Tilling, George Davey Smith, Michael C O’Donovan, Anita Thapar

Posted 02 Oct 2018
bioRxiv DOI: 10.1101/433342

Objective. Irritability 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' subtype with onset in childhood and a 'depression/mood' subtype with onset in adolescence. Method. Data 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). Psychiatric diagnoses were assessed at approximately ages 7 and 15 years. Psychiatric genetic risk was indexed by polygenic risk scores (PRS) for attention-deficit/hyperactivity disorder (ADHD) and major depressive disorder (MDD) 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 (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 MDD (OR=5.14 (2.47-10.73), p<0.001) and MDD PRS (OR=1.20, (1.05-1.38), p=0.009). Both trajectory classes were associated with MDD diagnosis and ADHD genetic risk. Conclusions. The developmental context of irritability may be important in its conceptualization: early-onset persistent irritability maybe more 'neurodevelopmental/ADHD-like' and later-onset irritability more 'depression/mood-like'. This has implications for treatment as well as nosology.

Download data

  • Downloaded 196 times
  • Download rankings, all-time:
    • Site-wide: 43,715 out of 62,198
    • In genetics: 2,661 out of 3,537
  • Year to date:
    • Site-wide: 30,760 out of 62,198
  • Since beginning of last month:
    • Site-wide: 16,693 out of 62,198

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News