Evaluating chronic emotional dysregulation and irritability in relation to ADHD and depression genetic risk in children with ADHD

Joel T. Nigg, Sarah L. Karalunas, Hanna C. Gustafsson, Priya Bhatt, Peter Ryabinin, Michael A. Mooney, Stephen V. Faraone, Damien A. Fair, Beth Wilmot

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Background: A central nosological problem concerns the etiological relationship of emotional dysregulation with ADHD. Molecular genetic risk scores provide a novel method for informing this question. Methods: Participants were 514 community-recruited children of Northern European descent age 7-11 defined as ADHD or non-ADHD by detailed research evaluation. Parents-rated ADHD on standardized ratings and child temperament on the Temperament in Middle Childhood Questionnaire (TMCQ) and reported on ADHD and comorbid disorders by semi-structured clinical interview. Categorical and dimensional variables were created for ADHD, emotional dysregulation (implicating disruption of regulation of both anger-irritability and of positive valence surgency-sensation seeking), and irritability alone (anger dysregulation). Genome-wide polygenic risk scores (PRS) were computed for ADHD and depression genetic liability. Structural equation models and computationally derived emotion profiles guided analysis. Results: The ADHD PRS was associated in variable-centered analyses with irritability (β =.179, 95% CI = 0.087–0.280; ΔR2 =.034, p <.0002), but also with surgency/sensation seeking (B =.146, 95%CI = 0.052–0.240, ΔR2=.022, p =.002). In person-centered analysis, the ADHD PRS was elevated in the emotion dysregulation ADHD group versus other ADHD children (OR = 1.44, 95% CI = 1.03–2.20, Nagelkerke ΔR2 =.013, p =.033) but did not differentiate irritable from surgent ADHD profiles. All effects were independent of variation in ADHD severity across traits or groups. The depression PRS was related to oppositional defiant disorder but not to ADHD emotion dysregulation. Conclusions: Irritability-anger and surgency-sensation seeking, as forms of negative and positively valenced dysregulated affect in ADHD populations, both relate principally to ADHD genetic risk and not mood-related genetic risk.

Original languageEnglish (US)
Pages (from-to)205-214
Number of pages10
JournalJournal of Child Psychology and Psychiatry and Allied Disciplines
Volume61
Issue number2
DOIs
StatePublished - Feb 1 2020
Externally publishedYes

Bibliographical note

Funding Information:
Support was provided by NIH R01‐MH099064 and R37‐MH‐59105. The authors thank Benjamin Neale, Ph.D. for consultation on methodology and analysis. D.A.F. is a founder of Nous Imaging, Inc. but its activities are unrelated to the current study, and any potential conflict of interest has been reviewed and managed by OHSU. S.V.F. has received grant or research support from the K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, the University of Bergen, Bergen, Norway, the European Union's Seventh Framework Programme for research, technological development, and demonstration, the European Union's Horizon 2020 research and innovation programme, and the National Institute of Mental Health. S.V.F. has received income, potential income, travel expenses, continuing education support, research support from, and/or has served on the advisory boards of/as a consultant to Lundbeck, Rhodes, Arbor, KenPharm, Ironshore, Neurovance, Impact, Takeda, Shire, Akili Interactive Labs, CogCubed, Alcobra, VAYA Pharma, Sunovion, Genomind, and NeuroLifeSciences. In previous years, S.V.F. has received income or research support from Shire, Neurovance, Alcobra, Otsuka, McNeil, Janssen, Novartis, Pfizer, and Eli Lilly and Co. S.V.F. has served as editor of the American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. S.V.F.'s institution (SUNY) has US patent US20130217707 A1 for the use of sodium‐hydrogen exchange inhibitors in the treatment of ADHD. S.V.F. has received royalties from books published by Guilford Press (Straight Talk about Your Child's Mental Health), Oxford University Press (Schizophrenia: The Facts), and Elsevier (ADHD: Non‐Pharmacologic Interventions). S.V.F. has held stock in CogCubed and Ironshore. S.V.F. is the principal investigator of http://adhdinadults.com/ . The remaining authors have declared that they have no competing or potential conflicts of interest.

Funding Information:
Support was provided by NIH R01-MH099064 and R37-MH-59105. The authors thank Benjamin Neale, Ph.D. for consultation on methodology and analysis. D.A.F. is a founder of Nous Imaging, Inc. but its activities are unrelated to the current study, and any potential conflict of interest has been reviewed and managed by OHSU. S.V.F. has received grant or research support from the K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, the University of Bergen, Bergen, Norway, the European Union's Seventh Framework Programme for research, technological development, and demonstration, the European Union's Horizon 2020 research and innovation programme, and the National Institute of Mental Health. S.V.F. has received income, potential income, travel expenses, continuing education support, research support from, and/or has served on the advisory boards of/as a consultant to Lundbeck, Rhodes, Arbor, KenPharm, Ironshore, Neurovance, Impact, Takeda, Shire, Akili Interactive Labs, CogCubed, Alcobra, VAYA Pharma, Sunovion, Genomind, and NeuroLifeSciences. In previous years, S.V.F. has received income or research support from Shire, Neurovance, Alcobra, Otsuka, McNeil, Janssen, Novartis, Pfizer, and Eli Lilly and Co. S.V.F. has served as editor of the American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. S.V.F.'s institution (SUNY) has US patent US20130217707 A1 for the use of sodium-hydrogen exchange inhibitors in the treatment of ADHD. S.V.F. has received royalties from books published by Guilford Press (Straight Talk about Your Child's Mental Health), Oxford University Press (Schizophrenia: The Facts), and Elsevier (ADHD: Non-Pharmacologic Interventions). S.V.F. has held stock in CogCubed and Ironshore. S.V.F. is the principal investigator of http://adhdinadults.com/. The remaining authors have declared that they have no competing or potential conflicts of interest.

Publisher Copyright:
© 2019 Association for Child and Adolescent Mental Health

Keywords

  • ADHD
  • irritability
  • polygenic score
  • temperament

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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