Vitamin D and the risk of treatment-resistant and atypical depression: A Mendelian randomization study

Abstract Observational evidence has implicated vitamin D levels as a risk factor in major depressive disorder (MDD). Confounding or reverse causation may be driving these observed associations, with studies using genetics indicating little evidence of an effect. However, genetic studies have relied...

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Autores principales:	Ryan Arathimos, Amy Ronaldson, Laurence J. Howe, Chiara Fabbri, Saskia Hagenaars, Matthew Hotopf, Fiona Gaughran, Cathryn M. Lewis, Alexandru Dregan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/5c91c03058a3487eb62677b185e5c3d3
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spelling	oai:doaj.org-article:5c91c03058a3487eb62677b185e5c3d32021-11-07T12:17:34ZVitamin D and the risk of treatment-resistant and atypical depression: A Mendelian randomization study10.1038/s41398-021-01674-32158-3188https://doaj.org/article/5c91c03058a3487eb62677b185e5c3d32021-11-01T00:00:00Zhttps://doi.org/10.1038/s41398-021-01674-3https://doaj.org/toc/2158-3188Abstract Observational evidence has implicated vitamin D levels as a risk factor in major depressive disorder (MDD). Confounding or reverse causation may be driving these observed associations, with studies using genetics indicating little evidence of an effect. However, genetic studies have relied on broad definitions of depression. The genetic architecture of different depression subtypes may vary since MDD is a highly heterogenous condition, implying potentially diverging requirements in therapeutic approaches. We explored the associations between vitamin D and two subtypes of MDD, for which evidence of a causal link could have the greatest clinical benefits: treatment-resistant depression (TRD) and atypical depression (AD). We used a dual approach, combining observational data with genetic evidence from polygenic risk scores (PRS) and two-sample Mendelian randomization (MR), in the UK Biobank. There was some evidence of a weak association between vitamin D and both incident TRD (Ncases = 830) and AD (Ncases = 2366) in observational analyses, which largely attenuated when adjusting for confounders. Genetic evidence from PRS and two-sample MR, did not support a causal link between vitamin D and either TRD (Ncases = 1891, OR = 1.01 [95%CI 0.78, 1.31]) or AD (Ncases = 2101, OR = 1.04 [95%CI 0.80, 1.36]). Our comprehensive investigations indicated some evidence of an association between vitamin D and TRD/AD observationally, but little evidence of association when using PRS and MR, mirroring findings of genetic studies of vitamin D on broad depression phenotypes. Results do not support further clinical trials of vitamin D in these MDD subtypes but do not rule out that small effects may exist that require larger samples to detect.Ryan ArathimosAmy RonaldsonLaurence J. HoweChiara FabbriSaskia HagenaarsMatthew HotopfFiona GaughranCathryn M. LewisAlexandru DreganNature Publishing GrouparticleNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENTranslational Psychiatry, Vol 11, Iss 1, Pp 1-7 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Ryan Arathimos Amy Ronaldson Laurence J. Howe Chiara Fabbri Saskia Hagenaars Matthew Hotopf Fiona Gaughran Cathryn M. Lewis Alexandru Dregan Vitamin D and the risk of treatment-resistant and atypical depression: A Mendelian randomization study
description	Abstract Observational evidence has implicated vitamin D levels as a risk factor in major depressive disorder (MDD). Confounding or reverse causation may be driving these observed associations, with studies using genetics indicating little evidence of an effect. However, genetic studies have relied on broad definitions of depression. The genetic architecture of different depression subtypes may vary since MDD is a highly heterogenous condition, implying potentially diverging requirements in therapeutic approaches. We explored the associations between vitamin D and two subtypes of MDD, for which evidence of a causal link could have the greatest clinical benefits: treatment-resistant depression (TRD) and atypical depression (AD). We used a dual approach, combining observational data with genetic evidence from polygenic risk scores (PRS) and two-sample Mendelian randomization (MR), in the UK Biobank. There was some evidence of a weak association between vitamin D and both incident TRD (Ncases = 830) and AD (Ncases = 2366) in observational analyses, which largely attenuated when adjusting for confounders. Genetic evidence from PRS and two-sample MR, did not support a causal link between vitamin D and either TRD (Ncases = 1891, OR = 1.01 [95%CI 0.78, 1.31]) or AD (Ncases = 2101, OR = 1.04 [95%CI 0.80, 1.36]). Our comprehensive investigations indicated some evidence of an association between vitamin D and TRD/AD observationally, but little evidence of association when using PRS and MR, mirroring findings of genetic studies of vitamin D on broad depression phenotypes. Results do not support further clinical trials of vitamin D in these MDD subtypes but do not rule out that small effects may exist that require larger samples to detect.
format	article
author	Ryan Arathimos Amy Ronaldson Laurence J. Howe Chiara Fabbri Saskia Hagenaars Matthew Hotopf Fiona Gaughran Cathryn M. Lewis Alexandru Dregan
author_facet	Ryan Arathimos Amy Ronaldson Laurence J. Howe Chiara Fabbri Saskia Hagenaars Matthew Hotopf Fiona Gaughran Cathryn M. Lewis Alexandru Dregan
author_sort	Ryan Arathimos
title	Vitamin D and the risk of treatment-resistant and atypical depression: A Mendelian randomization study
title_short	Vitamin D and the risk of treatment-resistant and atypical depression: A Mendelian randomization study
title_full	Vitamin D and the risk of treatment-resistant and atypical depression: A Mendelian randomization study
title_fullStr	Vitamin D and the risk of treatment-resistant and atypical depression: A Mendelian randomization study
title_full_unstemmed	Vitamin D and the risk of treatment-resistant and atypical depression: A Mendelian randomization study
title_sort	vitamin d and the risk of treatment-resistant and atypical depression: a mendelian randomization study
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/5c91c03058a3487eb62677b185e5c3d3
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Vitamin D and the risk of treatment-resistant and atypical depression: A Mendelian randomization study

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