Garcia-Argibay, Miguel, Brikell, Isabell, Thapar, Anita ORCID: https://orcid.org/0000-0002-3689-737X, Lichtenstein, Paul, Lundström, Sebastian, Demontis, Ditte and Larrson, Henrik 2024. Attention-deficit/hyperactivity disorder and major depressive disorder: Evidence from multiple genetically informed designs. Biological Psychiatry 95 (5) , pp. 444-452. 10.1016/j.biopsych.2023.07.017 |
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Abstract
Background Attention-deficit/hyperactivity disorder (ADHD) and major depressive disorder (MDD) are two highly prevalent disorders that frequently co-occur. Prior evidence from genetic and cohort studies supports an association between ADHD and MDD. However, the direction and mechanisms underlying their association remain unclear. As onset of ADHD occurs in early life, it has been hypothesized that ADHD may cause MDD. Methods We examined the association of ADHD with MDD using 3 different genetically informed methods to disentangle causality from confounding: 1) a nationwide longitudinal register-based full sibling comparison (N = 1,018,489) adjusting for shared familial confounding; 2) a prospective co-twin control study comprising 16,477 twins (5084 monozygotic and 11,393 dizygotic); and 3) a two-sample Mendelian randomization analysis using the largest available ADHD (N = 225,534) and MDD (N = 500,199) genome-wide association study summary statistics, adjusting for correlated and uncorrelated horizontal pleiotropy. Results Sibling and twin comparisons indicated that individuals with ADHD have an increased risk for subsequent development of MDD (hazard ratio = 4.12 [95% CI 3.62–4.69]) after adjusting for shared genetic and familial factors and that ADHD scores endorsed by parents are positively associated with subsequent MDD scores at ages 15 and 18 years (b = 0.07 [95% CI 0.05–0.08] and b = 0.09 [95% CI 0.08–0.11], respectively). Mendelian randomization analyses showed that genetic liability for ADHD is causally related to MDD (odds ratio = 1.15 [95% CI 1.08–1.23]). Conclusions Our study provides consistent results across 3 different genetically informative approaches, strengthening the hypothesis that ADHD is causally related to MDD.
Item Type: | Article |
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Date Type: | Publication |
Status: | Published |
Schools: | Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) |
Publisher: | Elsevier |
ISSN: | 0006-3223 |
Date of First Compliant Deposit: | 2 August 2023 |
Date of Acceptance: | 30 July 2023 |
Last Modified: | 07 Mar 2024 11:04 |
URI: | https://orca.cardiff.ac.uk/id/eprint/161427 |
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