Smoking Is Associated with, but Does Not Cause, Depressed Mood in Pregnancy – A Mendelian Randomization Study
Open accessAbstract
Smokers have a higher prevalence of major depressive episodes and depressive symptoms than the general population, but whether this association is causal, or is due to confounding or reverse causation is uncertain because of the problems inherent in some epidemiological studies. Mendelian randomization, in which a genetic variant is used as a surrogate for measuring exposure, is an approach which may be used to better understand this association. We investigated the rs1051730 single nucleotide polymorphism in the nicotine acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4), associated with smoking phenotypes, to determine whether women who continued to smoke were also more likely to report a low mood during pregnancy. We found among women who smoked pre-pregnancy, those with the 1051730 T allele smoked more and were less likely to quit smoking during pregnancy, but were also less likely to report high levels of depressed mood at 18 weeks of pregnancy (per allele OR = 0.84, 95%CI 0.72 to 0.99, p = 0.034). The association between genotype and depressed mood was limited to women who were smokers prior to pregnancy, with weak evidence of an interaction between smoking status and genotype (p = 0.07). Our results do not support a causal role of smoking on depressed mood, but are consistent with a self-medication hypothesis, whereby smoking is used to alleviate symptoms of depression. A replication study using multiple genetic variants which influence smoking via different pathways is required to confirm these findings and provide evidence that the genetic variant is reflecting the effect of quitting smoking on depressed mood, and is not directly affecting mood.
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No evidence for smoking increasing risk of antenatal depression in the ALSPAC cohort.
“No evidence for smoking increasing risk of antenatal depression was found in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (N=6,294) 48 .”
From A meta-review of "lifestyle psychiatry": the role of exercise, smoking, diet and sleep in the prevention and treatment of mental disorders (2020) · cites this paper as [48]
The Abstract reports that the ALSPAC results do not support a causal role for smoking in depressed mood during pregnancy, and the Results state that the analysis included 6,294 women. However, the Discussion says the study assessed self-reported depressed mood, not diagnosed depression; a high EPDS score does not constitute a depression diagnosis. (LLM, conf=0.85)
Experimental — accuracy not yet measuredInstrumental variables are widely used in econometric program evaluation and have attracted much recent interest in epidemiology, particularly in the context of Mendelian randomization studies, which use genetic variants as instruments for environmental exposures.
“IVs are widely used in econometric program evaluation and have attracted much recent interest in epidemiology, particularly in the context of Mendelian randomization studies, which use genetic variants as instruments for environmental exposures (25, 36, 48).”
From Natural Experiments: An Overview of Methods, Approaches, and Contributions to Public Health Intervention Research (2017) · cites this paper as [48]
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- Authors
- Lewis, S. J., Araya, R., Davey Smith, G., Freathy, R., Gunnell, D., Palmer, T., & Munafò, M.
- Affiliations
- University of Bristol (GB)
- University of Exeter (GB)
- Corresponding author
- Lewis, Sarah J.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-07-19
- Volume
- 6
- Issue
- 7
- Pages
- e21689
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3139580
- OpenAlex
- W2148509766
- Cited by
- 53
- References
- 18
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 4 · 2021: 3 · 2020: 4 · 2019: 3 · 2018: 2 · 2017: 5 · 2016: 5 · 2015: 8 · 2014: 9 · 2013: 5 · 2012: 3
- FWCI
- 3.71
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Lancaster EPrints (Lancaster University) (submittedVersion)
- Figshare (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Open Research Exeter (University of Exeter) (submittedVersion, other-oa)
- Bristol Research (University of Bristol) (submittedVersion)
- Funders
- Wellcome Trust (076467, G0600705, 092731, 74882)
- University of Bristol (74882, 076467, G0600705)
- Medical Research Council (74882, 076467, G0600705)
- Topics
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Keywords
- smoking during pregnancy, depressive mood, maternal depression, rs1051730, nicotinic acetylcholine receptors, smoking cessation, self-medication hypothesis, causal inference
- MeSH terms
- Affect, Depression, Female, Humans, Pregnancy, Risk Factors, Smoking, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Mendelian Randomization Analysis
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