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Depression and ADHD-Related Risk for Substance Use in Adolescence and Early Adulthood: Concurrent and Prospective Associations in the MTA

Abstract

Childhood attention-deficit/hyperactivity disorder (ADHD) is prospectively linked to substance use and disorder. Depression emerging in adolescence is an understudied risk factor that may explain some of this risk. In the present study, we considered mediating and moderating roles of adolescent depression in explaining this association by using longitudinal data from the prospective 16-year follow-up of the Multimodal Treatment Study of ADHD (MTA). Participants were 547 children diagnosed with DSM-IV ADHD Combined Type, and 258 age- and sex-matched comparison children. In adolescence, depressive symptoms did not exacerbate effects of childhood ADHD on any substance use. For both groups, time-varying and average depressive symptoms were associated with more frequent use of all substances. Prospectively, we found no evidence of depression mediation to adult substance use. However, adolescent depression moderated the association between childhood ADHD and adult marijuana use. Although adults without ADHD histories used marijuana more frequently if they had elevated depressive symptoms in adolescence, marijuana use by adults with ADHD histories was independent of their adolescent depression. In adulthood, depression diagnoses and ADHD persistence continued to operate as independent, additive correlates of substance use risk. Our findings suggest a circumscribed role for depression in substance use risk that adds to, but does not alter or explain, ADHD-related risk.

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Fig. 1

Notes

  1. Defined as one standard deviation above average depressive symptoms (.24) in adolescence. Odds ratio associated with the largest mediated effect in Table 1 = e(.15*.24)/[1 + e(.15*.24)] = 1.037 (i.e., odds are 3.7% higher).

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Acknowledgements

Collaborators formerly at NIMH: Benedetto Vitiello, (University of Turin); Joanne B. Severe; Peter S. Jensen (currently University of Arkansas); L. Eugene Arnold (currently Ohio State University); Kimberly Hoagwood, (currently Columbia); early-phase NIMH contributors: John Richters; Donald Vereen. Site PIs/Co-Is: University of California, Berkeley/San Francisco: Stephen P. Hinshaw (Berkeley), Glen R. Elliott (San Francisco); Duke University: Karen C. Wells; Jeffery N. Epstein (currently Cincinnati Children’s Hospital); Desiree W. Murray (currently UNC Chapel Hill); early-phase Duke contributors: C. Keith Conners; John March; University of California, Irvine: James Swanson, Timothy Wigal; UCLA contributor: Dennis P. Cantwell; NYU School of Medicine: Howard B. Abikoff; Montréal Children’s Hospital/McGill University: Lily Hechtman; NY State Psychiatric Institute/ Columbia University/Mount Sinai Medical Center: Laurence L. Greenhill; Jeffrey H. Newcorn; University of Pittsburgh: Brooke Molina; Betsy Hoza (University of Vermont); William E. Pelham (currently Florida International University). Follow-up statistical collaborators: Robert D. Gibbons (University of Illinois, Chicago); Sue Marcus (Mt. Sinai College of Medicine); Kwan Hur (University of Illinois, Chicago). Original study statistical/design consultant: Helena C. Kraemer (Stanford University). Collaborators from US Department of Education, Thomas Hanley and Karen Stern.

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Correspondence to Andrea L. Howard.

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Conflict of Interest

J.T.M. consulted with Avanir. L.E.A. received research funding from Forest, Lilly, Noven, Roche/Genentech, Shire, Supernus, and YoungLiving (as well as NIH and Autism Speaks), and consulted with Pfizer, Tris Pharma, and Waypoint, and been on advisory boards for Arbor, Ironshore, Otsuka, Pfizer, Roche/Genentech, Seaside Therapeutics, and Shire. J.M.S. acknowledges research support, advisory board/ speaker’s bureau and/or consulting for Alza, Richwood, Shire, Celgene, Novartis, Celltech, Gliatech, Cephalon, Watson, CIBA, UCB, Janssen, McNeil, Noven, NLS, Medice, and Lilly. J.N.E. received consulting fees from American Academy of Pediatrics and American Board of Pediatrics, received royalties from Multi-Health Systems, Optimal Medicine, and IXICO, and received research support from Akili Interactive Labs. A.R. was supported by an Alexander von Humboldt fellowship in 2017-2018. The other remaining authors have declared that they have no competing or potential conflicts of interest.

Ethical Approval

The Multimodal Treatment Study of Children with ADHD (MTA) was a National Institute of Mental Health (NIMH) cooperative agreement randomized clinical trial with the observational phase funded by NIMH and the National Institute on Drug Abuse (NIDA) to the following: University of California–Berkeley*: U01MH50461, N01MH12009, N01DA-8-5550; Duke University*: U01MH50477, N01MH12012, N01DA-8-5554; University of California, Irvine*: U01MH50440, N01MH12011, N01DA-8-5551; Research Foundation for Mental Hygiene (New York State Psychiatric Institute*/Columbia University): U01 MH50454, N01 MH12007, N01DA-8- 5552; Long Island–Jewish Medical Center*: U01 MH50453; New York University: N01MH 12,004, N01DA-8-5549; University of Pittsburgh*: U01 MH50467, N01MH 12,010, N01DA-8-5553; McGill University N01MH12008, N01DA-8-5548. A data analysis grant awarded to the University of Pittsburgh (DA039881) followed. IRB ethics approvals for primary data collection at the RCT and observational phases were obtained from all above sites marked with an asterisk* as well as at Mount Sinai Medical Center and Montréal Children’s Hospital. The opinions and assertions contained in this report are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of Health and Human Services, the National Institutes of Health or the National Institute of Mental Health.

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Informed consent (parental permission and child assent) was obtained from all participating families prior to completing study procedures. Once they reached age 18, participants provided their own informed consent. All participating study sites (see Author note for a detailed list) obtained IRB ethics approval. Secondary data analysis procedures were approved by the Carleton University Research Ethics Board.

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Howard, A.L., Kennedy, T.M., Macdonald, E.P. et al. Depression and ADHD-Related Risk for Substance Use in Adolescence and Early Adulthood: Concurrent and Prospective Associations in the MTA. J Abnorm Child Psychol 47, 1903–1916 (2019). https://doi.org/10.1007/s10802-019-00573-y

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Keywords

  • ADHD
  • Depression
  • Substance use
  • Adolescence
  • Early adulthood
  • Longitudinal