Clinical and Genetic Correlates of Bipolar Disorder With Childhood-Onset Attention Deficit Disorder

Nicolas A. Nunez, Brandon J. Coombes, Francisco Romo-Nava, David J. Bond, Jennifer Vande Voort, Paul E. Croarkin, Nicole Leibman, Manuel Gardea Resendez, Marin Veldic, Hannah Betcher, Balwinder Singh, Colin Colby, Alfredo Cuellar-Barboza, Miguel Prieto, Katherine M. Moore, Aysegul Ozerdem, Susan L. McElroy, Mark A. Frye, Joanna M. Biernacka

Research output: Contribution to journalArticlepeer-review


Background: Bipolar disorder (BD) with co-occurring attention deficit-hyperactivity disorder (ADHD) is associated with an unfavorable course of illness. We aimed to identify potential clinical and genetic correlates of BD with and without ADHD.

Methods: Among patients with BD ( N = 2,198) enrolled in the Mayo Clinic Bipolar Biobank we identified those with ADHD diagnosed in childhood (BD+cADHD; N = 350), those with adult-onset attention deficit symptoms (BD+aAD; N = 254), and those without ADHD ( N = 1,594). We compared the groups using linear or logistic regression adjusting for age, sex, and recruitment site. For genotyped patients ( N = 1,443), logistic regression was used to compare ADHD and BD polygenic risk scores (PRSs) between the BD groups, as well as to non-BD controls ( N = 777).

Results: Compared to the non-ADHD BD group, BD+cADHD patients were younger, more often men and had a greater number of co-occurring anxiety and substance use disorders (all p < 0.001). Additionally, BD+cADHD patients had poorer responses to lithium and lamotrigine ( p = 0.005 and p = 0.007, respectively). In PRS analyses, all BD patient subsets had greater genetic risk for BD and ADHD when compared to non-BD controls ( p < 0.001 in all comparisons). BD+cADHD patients had a higher ADHD-PRS than non-ADHD BD patients ( p = 0.012). However, BD+aAD patients showed no evidence of higher ADHD-PRS than non-ADHD BD patients ( p = 0.38).

Conclusions: BD+cADHD was associated with a greater number of comorbidities and reduced response to mood stabilizing treatments. The higher ADHD PRS for the BD+cADHD group may reflect a greater influence of genetic factors on early presentation of ADHD symptoms.

Original languageEnglish (US)
Article number884217
JournalFrontiers in Psychiatry
StatePublished - Apr 14 2022

Bibliographical note

Funding Information:
This research was supported by Mayo Clinic benefactors and the Mayo Clinic Center for Individualized Medicine.

Publisher Copyright:
Copyright © 2022 Nunez, Coombes, Romo-Nava, Bond, Vande Voort, Croarkin, Leibman, Gardea Resendez, Veldic, Betcher, Singh, Colby, Cuellar-Barboza, Prieto, Moore, Ozerdem, McElroy, Frye and Biernacka.


  • ADHD
  • bipolar disorder
  • clinical features
  • genetic
  • polygenic risk score

PubMed: MeSH publication types

  • Journal Article


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