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

Abstract

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.

Mental health in a diverse sample of healthcare workers during the COVID-19 pandemic: cross-sectional analysis of the UK-REACH study

“…Our study has limitations: in all cross-sectional studies, associations may be bidirectional, or due to reverse causation, e.g. smoking and mental health, 33 religiosity and PTSD 34 . Moreover, although the breadth of UK-REACH data permitted adjustment for hypothesised confounders, residual confounding (due to missing data or measurement error) is possible in all observational studies.…”

Applications of Mendelian randomization in psychiatry: a comprehensive systematic review

“…We included in this section and heterogeneous group of nine articles that focused on psychiatric diseases not included in previous tables (Table 4) (Wium-Andersen et al , 2015a; Jang et al , 2020; Jefsen et al , 2021; Jin et al , 2021; Rosoff et al , 2021; Vermeulen et al , 2021; Zhao et al , 2021; Chen et al , 2022; Ni et al , 2022). Among these, we included three studies on BD (Wium-Andersen et al , 2016; Jefsen et al , 2021; Vermeulen et al , 2021).…”

Effectiveness of Mental Health Warnings on Tobacco Packaging in People With and Without Common Mental Health Conditions: An Online Randomised Experiment

“…The final set of MHWLs to be implemented in the online experiment was guided by a patient and public consultancy group. The MHWLs were informed by causal evidence of the effect of smoking on mental health (22)(23)(24)(25). The MHWLs were approved by three members of the public with lived experience of smoking and/or mental health in a consultancy focus group, which involved deep discussions around both the text and pictures to be selected for the current study.…”

“…However, it is less well known amongst the general public and healthcare professionals that smoking can negatively affect mental health (19)(20)(21). A large body of evidence suggests that tobacco use increases the risk of developing depression, schizophrenia and bipolar disorder (22)(23)(24)(25), and that smoking cessation can reduce symptoms of depression, anxiety, and stress, and lead to improved wellbeing and positive feelings (26). Qualitative research suggests that people who smoke and have mental health conditions "buy in" to the idea that tobacco can worsen mental health, they understand that smoking can make their depression and anxiety worse, and that quitting could improve their mental health (27).…”