Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Attention-deficit/hyperactivity disorder and major depressive disorder: Evidence from multiple genetically informed designs

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

[thumbnail of Fig2.pdf] PDF - Supplemental Material
Available under License Creative Commons Attribution.

Download (16kB)
[thumbnail of Fig1.pdf] PDF - Supplemental Material
Available under License Creative Commons Attribution.

Download (76kB)
[thumbnail of PIIS0006322323014622.pdf]
Preview
PDF - Published Version
Available under License Creative Commons Attribution.

Download (358kB) | Preview

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
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

Citation Data

Cited 5 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics