Using Mendelian randomization analysis to better understand the relationship between mental health and substance use: a systematic review

Jorien L Treur, Marcus R Munafò, Emma Logtenberg, Reinout W Wiers, Karin J H Verweij

Research output: Contribution to journalArticle (Academic Journal)peer-review

7 Citations (Scopus)
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BACKGROUND: Poor mental health has consistently been associated with substance use (smoking, alcohol drinking, cannabis use, and consumption of caffeinated drinks). To properly inform public health policy it is crucial to understand the mechanisms underlying these associations, and most importantly, whether or not they are causal.

METHODS: In this pre-registered systematic review, we assessed the evidence for causal relationships between mental health and substance use from Mendelian randomization (MR) studies, following PRISMA. We rated the quality of included studies using a scoring system that incorporates important indices of quality, such as the quality of phenotype measurement, instrument strength, and use of sensitivity methods.

RESULTS: Sixty-three studies were included for qualitative synthesis. The final quality rating was '-' for 16 studies, '- +' for 37 studies, and '+'for 10 studies. There was robust evidence that higher educational attainment decreases smoking and that there is a bi-directional, increasing relationship between smoking and (symptoms of) mental disorders. Another robust finding was that higher educational attainment increases alcohol use frequency, but decreases binge-drinking and alcohol use problems, and that mental disorders causally lead to more alcohol drinking without evidence for the reverse.

CONCLUSIONS: The current MR literature increases our understanding of the relationship between mental health and substance use. Bi-directional causal relationships are indicated, especially for smoking, providing further incentive to strengthen public health efforts to decrease substance use. Future MR studies should make use of large(r) samples in combination with detailed phenotypes, a wide range of sensitivity methods, and triangulate with other research methods.

Original languageEnglish
Pages (from-to)1593-1624
Number of pages32
JournalPsychological Medicine
Issue number10
Early online date25 May 2021
Publication statusPublished - Jul 2021

Bibliographical note

Funding Information:
Financial support. JLT was supported by a Veni grant from the Netherlands Organization for Scientific Research (NWO; grant number 016.Veni.195.016). KJHV and JLT were supported by the Foundation Volksbond Rotterdam.

Publisher Copyright:
Copyright © The Author(s), 2021. Published by Cambridge University Press.


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