AUTHOR=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. 

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

JOURNAL=Frontiers in Psychiatry

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2022.884217

DOI=10.3389/fpsyt.2022.884217

ISSN=1664-0640

ABSTRACT=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=2198) 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=1594). We compared the groups using linear or logistic regression adjusting for age, sex, and recruitment site. For genotyped patients (N=1443), 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.