1. The Relationship of Attention-Deficit/Hyperactivity Disorder With Posttraumatic Stress Disorder
- Author
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Frank R. Wendt, Miguel Garcia-Argibay, Brenda Cabrera-Mendoza, Unnur A. Valdimarsdóttir, Joel Gelernter, Murray B. Stein, Michel G. Nivard, Adam X. Maihofer, Caroline M. Nievergelt, Henrik Larsson, Manuel Mattheisen, Renato Polimanti, Sandra M. Meier, Karmel W. Choi, Jonathan R.I. Coleman, Nikolaos P. Daskalakis, Christy A. Denckla, Elizabeth Ketema, Rajendra A. Morey, Andrew Ratanatharathorn, Katy Torres, Aliza P. Wingo, Clement C. Zai, Allison E. Aiello, Lynn M. Almli, Ananda B. Amstadter, Soren B. Andersen, Ole A. Andreassen, Paul A. Arbisi, Allison E. Ashley-Koch, S. Bryn Austin, Esmina Avdibegovic, Anders D. Borglum, Dragan Babic, Marie Bækvad-Hansen, Dewleen G. Baker, Jean C. Beckham, Laura J. Bierut, Jonathan I. Bisson, Marco P. Boks, Elizabeth A. Bolger, Bekh Bradley, Meghan Brashear, Gerome Breen, Richard A. Bryant, Angela C. Bustamante, Jonas Bybjerg-Grauholm, Joseph R. Calabrese, Jose Miguel Caldas-de-Almeida, Chia-Yen Chen, Anders M. Dale, Shareefa Dalvie, Jürgen Deckert, Douglas L. Delahanty, Michelle F. Dennis, Seth G. Disner, Katharina Domschke, Laramie E. Duncan, Alma Dzubur Kulenovic, Christopher R. Erbes, Alexandra Evans, Lindsay A. Farrer, Norah C. Feeny, Janine D. Flory, David Forbes, Carol E. Franz, Sandro Galea, Melanie E. Garrett, Aarti Gautam, Bizu Gelaye, Elbert Geuze, Charles F. Gillespie, Aferdita Goci Uka, Scott D. Gordon, Guia Guffanti, Rasha Hammamieh, Michael A. Hauser, Andrew C. Heath, Sian M.J. Hemmings, David Michael Hougaard, Miro Jakovljevic, Marti Jett, Eric Otto Johnson, Ian Jones, Tanja Jovanovic, Xue-Jun Qin, Karen-Inge Karstoft, Milissa L. Kaufman, Ronald C. Kessler, Alaptagin Khan, Nathan A. Kimbrel, Anthony P. King, Nastassja Koen, Henry R. Kranzler, William S. Kremen, Bruce R. Lawford, Lauren A.M. Lebois, Catrin Lewis, Israel Liberzon, Sarah D. Linnstaedt, Mark W. Logue, Adriana Lori, Bozo Lugonja, Jurjen J. Luykx, Michael J. Lyons, Jessica L. Maples-Keller, Charles Marmar, Nicholas G. Martin, Douglas Maurer, Matig R. Mavissakalian, Alexander McFarlane, Regina E. McGlinchey, Katie A. McLaughlin, Samuel A. McLean, Divya Mehta, Rebecca Mellor, Vasiliki Michopoulos, William Milberg, Mark W. Miller, Charles Phillip Morris, Ole Mors, Preben Bo Mortensen, Elliot C. Nelson, Merete Nordentoft, Sonya B. Norman, Meaghan O’Donnell, Holly K. Orcutt, Matthew S. Panizzon, Edward S. Peters, Alan L. Peterson, Matthew Peverill, Robert H. Pietrzak, Melissa A. Polusny, John P. Rice, Victoria B. Risbrough, Andrea L. Roberts, Alex O. Rothbaum, Barbara O. Rothbaum, Peter Roy-Byrne, Kenneth J. Ruggiero, Ariane Rung, Bart P.F. Rutten, Nancy L. Saccone, Sixto E. Sanchez, Dick Schijven, Soraya Seedat, Antonia V. Seligowski, Julia S. Seng, Christina M. Sheerin, Derrick Silove, Alicia K. Smith, Jordan W. Smoller, Scott R. Sponheim, Dan J. Stein, Jennifer S. Stevens, Martin H. Teicher, Wesley K. Thompson, Edward Trapido, Monica Uddin, Robert J. Ursano, Leigh Luella van den Heuvel, Miranda Van Hooff, Eric Vermetten, Christiaan Vinkers, Joanne Voisey, Yunpeng Wang, Zhewu Wang, Thomas Werge, Michelle A. Williams, Douglas E. Williamson, Sherry Winternitz, Christiane Wolf, Erika J. Wolf, Rachel Yehuda, Keith A. Young, Ross McD. Young, Hongyu Zhao, Lori A. Zoellner, Magali Haas, Heather Lasseter, Allison C. Provost, Rany M. Salem, Jonathan Sebat, Richard Shaffer, Tianying Wu, Stephan Ripke, Mark J. Daly, Kerry J. Ressler, Karestan C. Koenen, Biological Psychology, APH - Mental Health, APH - Methodology, Anatomy and neurosciences, Psychiatry, and Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep
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Genome-wide association study ,Epidemiology ,Siblings ,PTSD ,Mendelian Randomization Analysis ,Comorbidities ,SDG 3 - Good Health and Well-being ,Humans ,ADHD ,Attention Deficit Disorder with Hyperactivity/epidemiology ,Stress Disorders, Post-Traumatic/genetics ,Biological Psychiatry ,Causal inference - Abstract
Background: Attention-deficit/hyperactivity disorder (ADHD) and posttraumatic stress disorder (PTSD) are associated, but it is unclear if this is a causal relationship or confounding. We used genetic analyses and sibling comparisons to clarify the direction of this relationship. Methods: Linkage disequilibrium score regression and 2-sample Mendelian randomization were used to test for genetic correlation (r g) and bidirectional causal effects using European ancestry genome-wide association studies of ADHD (20,183 cases and 35,191 controls) and 6 PTSD definitions (up to 320,369 individuals). Several additional variables were included in the analysis to verify the independence of the ADHD-PTSD relationship. In a population-based sibling comparison (N = 2,082,118 individuals), Cox regression models were fitted to account for time at risk, a range of sociodemographic factors, and unmeasured familial confounders (via sibling comparisons). Results: ADHD and PTSD had consistent r g (r g range, 0.43–0.52; p < .001). ADHD genetic liability was causally linked with increased risk for PTSD (β = 0.367; 95% CI, 0.186–0.552; p = 7.68 × 10 −5). This result was not affected by heterogeneity, horizontal pleiotropy (Mendelian randomization Egger intercept = 4.34 × 10 −4, p = .961), or other phenotypes and was consistent across PTSD datasets. However, we found no consistent associations between PTSD genetic liability and ADHD risk. Individuals diagnosed with ADHD were at a higher risk for developing PTSD than their undiagnosed sibling (hazard ratio = 2.37; 95% CI, 1.98–3.53). Conclusions: Our findings add novel evidence supporting the need for early and effective treatment of ADHD, as patients with this diagnosis are at significantly higher risk to develop PTSD later in life.
- Published
- 2023