Retrospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatr. Dec 22, 2015; 5(4): 412-424
Published online Dec 22, 2015. doi: 10.5498/wjp.v5.i4.412
Risk for emerging bipolar disorder, variants, and symptoms in children with attention deficit hyperactivity disorder, now grown up
Ahmed Z Elmaadawi, Peter S Jensen, L Eugene Arnold, Brooke SG Molina, Lily Hechtman, Howard B Abikoff, Stephen P Hinshaw, Jeffrey H Newcorn, Laurence Lee Greenhill, James M Swanson, Cathryn A Galanter
Ahmed Z Elmaadawi, Department of Psychiatry, Indiana University School of Medicine- South Bend Campus, South Bend, IN 46601, United States
Peter S Jensen, REACH Institute, New York, NY 10029, United States
L Eugene Arnold, Department of Psychiatry, Ohio State University, Columbus, OH 43219, United States
Brooke SG Molina, Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, United States
Lily Hechtman, Department of Psychiatry and Pediatrics, McGill University Health Center, Montreal, Quebec H2X 3J4, Canada
Howard B Abikoff, Department of Child and Adolescent Psychiatry, The Child Study Center at NYU Langone Medical Center, New York, NY 10016, United States
Stephen P Hinshaw, Department of Psychology, University of California, Berkeley, CA 94305, United States
Jeffrey H Newcorn, Department of Psychiatry and Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
Laurence Lee Greenhill, Department of Clinical Child and Adolescent Psychiatry, New York Psychiatric Institute, New York, NY 10029, United States
James M Swanson, Department of Pediatrics and Epidemiology, Child Development Center, University of California, Irvine, CA 94305, United States
Cathryn A Galanter, Department of Psychiatry, State University of New York Downstate Medical Center and Kings County Hospital Center, Brooklyn, NY 11203, United States
Author contributions: Elmaadawi AZ and Jensen PS designed research; Elmaadawi AZ and Jensen PS performed research; Jensen PS contributed to the new reagents or analytic tools; Elmaadawi AZ, Jensen PS, Arnold LE, Molina BSG and Swanson JM analyzed data; Elmaadawi AZ, Jensen PS, Arnold LE, Molina BSG, Hechtman L, Abikoff HB, Hinshaw SP, Newcorn JH, Greenhill LL, Swanson MJ and Galanter CA wrote the paper.
Institutional review board statement: IRB approval by the Mayo Clinic IRB board with IRB number 12-007481 last approval date 10/31/2014 and active till 10/30/2015.
Informed consent statement: Informed consent statement and data transfer agreements were obtained during the original MTA study design in 1995.
Conflict-of-interest statement: Dr. Ahmed Elmaadawi, the corresponding author, has no conflict of interest to disclose. Dr. Peter Jensen received funds from the followings: REACH Institute Employee, Mayo Clinic Consultant, Shire Pharmaceuticals, Inc., Grant Support and Honorarium for participation in another meeting and CATCH Services Member, Board of Governors and Stock or Equity. Dr. L Eugene Arnold Dr. Arnold has received research funding from Curemark, Forest, Lilly, Neuropharm, Novartis, Noven, Shire, and YoungLiving (as well as NIH and Autism Speaks) and has consulted with or been on advisory boards for Arbor, Gowlings, Neuropharm, Novartis, Noven, Organon, Otsuka, Pfizer, Roche, Seaside Therapeutics, Sigma Tau, Shire, and Tris Pharma and received travel support from Noven. Dr. Brooke Molina has no conflict of interest to disclose. Dr. Lily Hechtman has funds from Eli Lilly and Company Advisory Board and Research Support, Shire Pharmaceuticals, Inc. Advisory Board and Research Support Purdue Pharma L.P. Advisory Board and Research Support Janssen Pharmaceuticals, Inc. Advisory Board and Research Support. Dr. Howard B. Abikoff has no conflict of interest to disclose. Dr. Stephen P. Hinshaw has no conflict of interest to disclose. Dr. Jeffrey H. Newcorn has no conflict of interest to disclose. Dr. Laurence Lee Greenhill has following funds: Shire Pharmaceuticals, Inc. Research Support, BioBehavioral Diagnostics Company Advisory Board National Institute on Drug Abuse Grant Support. Dr. James M. Swanson has no conflict of interest to disclose. Dr. Cathryn A. Galanter has following conflict of interest to disclose The REACH Institute Consultant, American Psychiatric Publishing Royalties.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at aelmaada@iupui.edu. Consent was not obtained but the presented data are anonymized and risk of identification is low.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Ahmed Z Elmaadawi, Assistant Professor, Department of Psychiatry, Indiana University School of Medicine, 707 N. Michigan Street, Suite 400, South Bend, IN 46601, United States. aelmaada@iupui.edu
Telephone: +1-502-4570711 Fax: +1-574-6478740
Received: April 14, 2015
Peer-review started: April 24, 2015
First decision: June 3, 2015
Revised: September 2, 2015
Accepted: October 12, 2015
Article in press: October 13, 2015
Published online: December 22, 2015
Processing time: 248 Days and 10.3 Hours
Abstract

AIM: To determine the prevalence of bipolar disorder (BD) and sub-threshold symptoms in children with attention deficit hyperactivity disorder (ADHD) through 14 years’ follow-up, when participants were between 21-24 years old.

METHODS: First, we examined rates of BD type I and II diagnoses in youth participating in the NIMH-funded Multimodal Treatment Study of ADHD (MTA). We used the diagnostic interview schedule for children (DISC), administered to both parents (DISC-P) and youth (DISCY). We compared the MTA study subjects with ADHD (n = 579) to a local normative comparison group (LNCG, n = 289) at 4 different assessment points: 6, 8, 12, and 14 years of follow-ups. To evaluate the bipolar variants, we compared total symptom counts (TSC) of DSM manic and hypomanic symptoms that were generated by DISC in ADHD and LNCG subjects. Then we sub-divided the TSC into pathognomonic manic (PM) and non-specific manic (NSM) symptoms. We compared the PM and NSM in ADHD and LNCG at each assessment point and over time. We also evaluated the irritability as category A2 manic symptom in both groups and over time. Finally, we studied the irritability symptom in correlation with PM and NSM in ADHD and LNCG subjects.

RESULTS: DISC-generated BD diagnosis did not differ significantly in rates between ADHD (1.89%) and LNCG 1.38%). Interestingly, no participant met BD diagnosis more than once in the 4 assessment points in 14 years. However, on the symptom level, ADHD subjects reported significantly higher mean TSC scores: ADHD 3.0; LNCG 1.7; P < 0.001. ADHD status was associated with higher mean NSM: ADHD 2.0 vs LNCG 1.1; P < 0.0001. Also, ADHD subjects had higher PM symptoms than LNCG, with PM means over all time points of 1.3 ADHD; 0.9 LNCG; P = 0.0001. Examining both NSM and PM, ADHD status associated with greater NSM than PM. However, Over 14 years, the NSM symptoms declined and changed to PM over time (df 3, 2523; F = 20.1; P < 0.0001). Finally, Irritability (BD DSM criterion-A2) rates were significantly higher in ADHD than LNCG (χ2 = 122.2, P < 0.0001), but irritability was associated more strongly with NSM than PM (df 3, 2538; F = 43.2; P < 0.0001).

CONCLUSION: Individuals with ADHD do not appear to be at significantly greater risk for developing BD, but do show higher rates of BD symptoms, especially NSM. The greater linkage of irritability to NSM than to PM suggests caution when making BD diagnoses based on irritability alone as one of 2 (A-level) symptoms for BD diagnosis, particularly in view of its frequent presentation with other psychopathologies.

Keywords: Multimodal treatment study of attention deficit hyperactivity disorder, Irritability, Attention deficit hyperactivity disorder, Diagnostic interview schedule for children, Bipolar disorder

Core tip: Despite its formal DSM delineation, alternative pediatric bipolar disorder (BD) definitions have been debated for decades. Some research suggests that attention deficit hyperactivity disorder (ADHD) poses a risk for BD and that pediatric BD presents differently as non-episodic, greater chronicity, and more frequent irritability. In our study, we found the ADHD status is not a risk factor for developing BD over 14 years of follow-ups. When we controlled for overlapping ADHD/BD, nonspecific symptoms showed decreasing rates of BD in ADHD-diagnosed children. Clinicians are encouraged to pay greater attention to specific symptoms of mania in order to establish an accurate BD diagnosis. Furthermore, irritability (DSM criteria A2), was a nonspecific symptom of mania and linked to common psychopathologies in the early development of these children.