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=13

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