Investigating the causal relationship between neuroticism and depression via Mendelian randomization
Open accessAbstract
Neuroticism is a heritable personality trait, characterized by negative emotions such as worrying, feelings of guilt, loneliness and being easily hurt. Increased levels of neuroticism are associated with poor mental health - development of depression in particular - but it remains uncertain whether this association represents a causal effect [1]. Here, we use Mendelian randomization (MR) to investigate whether neuroticism is a causal risk factor for development of depression. This article is protected by copyright. All rights reserved.
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Several emotional states and traits, such as neuroticism, negative self-concept (with self-perceptions of worthlessness and uselessness), and negative interpretation or attention biases have been linked to depression.
“Several emotional states and traits, such as neuroticism [235,260,271,278], negative self-concept (with self-perceptions of worthlessness and uselessness), and negative interpretation or attention biases have been linked to depression [261,271,282,283,286].”
From Biological, Psychological, and Social Determinants of Depression: A Review of Recent Literature (2021) · cites this paper as [260]
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The MR-Base platform supports systematic causal inference across the human phenome
Hemani, G., Zheng, J., Elsworth, B., Wade, K. H., Haberland, V., Baird, D., Laurin, C., Burgess, S., Bowden, J., Langdon, R., et al. (2018) · eLife · doi:10.7554/elife.34408 · Cited by 7,959 · see citing works
Self-citationeQTLGen, Wray, N. R., 23andMe, the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Ripke, S., Mattheisen, M., Trzaskowski, M., Byrne, E. M., Abdellaoui, A., Adams, M. J., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0090-3 · Cited by 3,005 · see citing works
Self-citationNagel, M., Jansen, P. R., Stringer, S., Watanabe, K., de Leeuw, C., Bryois, J., Savage, J. E., Hammerschlag, A. R., Skene, N., Muñoz‐Manchado, A. B., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0151-7 · Cited by 806 · see citing works
Personality and Major Depression: A Swedish Longitudinal, Population-Based Twin Study
Kendler, K. S., Gatz, M., Gardner, C. O., & Pedersen, N. L. (2006) · Archives of General Psychiatry · doi:10.1001/archpsyc.63.10.1113 · Cited by 663 · see citing works
Item-level analyses reveal genetic heterogeneity in neuroticism
Nagel, M., Watanabe, K., Stringer, S., Posthuma, D., & van der Sluis, S. (2018) · Nature Communications · doi:10.1038/s41467-018-03242-8 · Cited by 279 · see citing works
Neuroticism as a mediator of treatment response to SSRIs in major depressive disorder
Quilty, L. C., Meusel, L.-A., & Bagby, R. M. (2008) · Journal of Affective Disorders · doi:10.1016/j.jad.2008.02.006 · Cited by 145 · see citing works
Depression History, Depression Vulnerability, and the Experience of Everyday Negative Events
O’Grady, M. A., Tennen, H. A., & Armeli, S. (2010) · Journal of Social and Clinical Psychology · doi:10.1521/jscp.2010.29.9.949 · Cited by 25 · see citing works
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Biological, Psychological, and Social Determinants of Depression: A Review of Recent Literature
Remes, O., Mendes, J. F., & Templeton, P. (2021) · Brain Sciences · doi:10.3390/brainsci11121633 · Cited by 482 · see citing works
- Authors
- Speed, D., Hemani, G., Speed, M. S., Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Børglum, A. D., & Østergaard, S. D.
- Affiliations
- Aarhus University (DK)
- University of Bristol (GB)
- Corresponding author
- Østergaard, S. D.
- Venue
- Acta Psychiatrica Scandinavica
- Publisher
- Wiley
- Published
- 2019-02-17
- Volume
- 139
- Issue
- 4
- Pages
- 395-397
- ISSN
- 0001-690X (ISSN-L)
- 1600-0447
- PMC
- PMC6426667
- OpenAlex
- W2914011140
- Cited by
- 38
- References
- 7
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 12 · 2023: 6 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 3
- FWCI
- 1.79
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Acta Psychiatrica Scandinavica (publishedVersion)
- PubMed (publishedVersion)
- Explore Bristol Research (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Bristol Research (University of Bristol) (acceptedVersion, other-oa)
- Funders
- H2020 Marie Skłodowska-Curie Actions (754513)
- National Institute of Mental Health (1U01MH109514‐01)
- Wellcome Trust (208806/Z/17/Z)
- Aarhus Universitets Forskningsfond (AUFF‐E‐2015‐FLS‐7‐2)
- Lundbeckfonden (R102‐A9118, R155‐2014‐1724, R165‐2013‐15320)
- Danmarks Frie Forskningsfond (7016‐00048, 7025‐00094B)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Social Sciences › Psychology › Clinical Psychology › Personality Traits and Psychology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- neuroticism, depression, causal relationship, personality traits, heritability, mental health, risk factors
- MeSH terms
- Neuroticism, Depression, Major Depressive Disorder, Humans, Risk Factors, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Mendelian Randomization Analysis
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