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

• Published in: Frontiers in psychiatry 2022-04, Vol.13, p.884217
• Main Authors: Nunez, Nicolas A, Coombes, Brandon J, Romo-Nava, Francisco, Bond, David J, Vande Voort, Jennifer, Croarkin, Paul E, Leibman, Nicole, Gardea Resendez, Manuel, Veldic, Marin, Betcher, Hannah, Singh, Balwinder, Colby, Colin, Cuellar-Barboza, Alfredo, Prieto, Miguel, Moore, Katherine M, Ozerdem, Aysegul, McElroy, Susan L, Frye, Mark A, Biernacka, Joanna M
• Format: Article
• Language: English
• Subjects: ADHD; bipolar disorder; clinical features; genetic; polygenic risk score; Psychiatry
• ISSN: 1664-0640; 1664-0640
• DOI: 10.3389/fpsyt.2022.884217

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. Among patients with BD ( = 2,198) enrolled in the Mayo Clinic Bipolar Biobank we identified those with ADHD diagnosed in childhood (BD+cADHD; = 350), those with adult-onset attention deficit symptoms (BD+aAD; = 254), and those without ADHD ( = 1,594). We compared the groups using linear or logistic regression adjusting for age, sex, and recruitment site. For genotyped patients ( = 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 ( = 777). 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 < 0.001). Additionally, BD+cADHD patients had poorer responses to lithium and lamotrigine ( = 0.005 and = 0.007, respectively). In PRS analyses, all BD patient subsets had greater genetic risk for BD and ADHD when compared to non-BD controls ( < 0.001 in all comparisons). BD+cADHD patients had a higher ADHD-PRS than non-ADHD BD patients ( = 0.012). However, BD+aAD patients showed no evidence of higher ADHD-PRS than non-ADHD BD patients ( = 0.38). 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.