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Understanding the nature of association between anxiety phenotypes and anorexia nervosa: a triangulation approach

BACKGROUND: Evidence from observational studies suggests an association between anxiety disorders and anorexia nervosa (AN), but causal inference is complicated by the potential for confounding in these studies. We triangulate evidence across a longitudinal study and a Mendelian randomization (MR) s...

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Autores principales: Lloyd, E. Caitlin, Sallis, Hannah M., Verplanken, Bas, Haase, Anne M., Munafò, Marcus R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542378/
https://www.ncbi.nlm.nih.gov/pubmed/33028263
http://dx.doi.org/10.1186/s12888-020-02883-8
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author Lloyd, E. Caitlin
Sallis, Hannah M.
Verplanken, Bas
Haase, Anne M.
Munafò, Marcus R.
author_facet Lloyd, E. Caitlin
Sallis, Hannah M.
Verplanken, Bas
Haase, Anne M.
Munafò, Marcus R.
author_sort Lloyd, E. Caitlin
collection PubMed
description BACKGROUND: Evidence from observational studies suggests an association between anxiety disorders and anorexia nervosa (AN), but causal inference is complicated by the potential for confounding in these studies. We triangulate evidence across a longitudinal study and a Mendelian randomization (MR) study, to evaluate whether there is support for anxiety disorder phenotypes exerting a causal effect on AN risk. METHODS: Study One assessed longitudinal associations of childhood worry and anxiety disorders with lifetime AN in the Avon Longitudinal Study of Parents and Children cohort. Study Two used two-sample MR to evaluate: causal effects of worry, and genetic liability to anxiety disorders, on AN risk; causal effects of genetic liability to AN on anxiety outcomes; and the causal influence of worry on anxiety disorder development. The independence of effects of worry, relative to depressed affect, on AN and anxiety disorder outcomes, was explored using multivariable MR. Analyses were completed using summary statistics from recent genome-wide association studies. RESULTS: Study One did not support an association between worry and subsequent AN, but there was strong evidence for anxiety disorders predicting increased risk of AN. Study Two outcomes supported worry causally increasing AN risk, but did not support a causal effect of anxiety disorders on AN development, or of AN on anxiety disorders/worry. Findings also indicated that worry causally influences anxiety disorder development. Multivariable analysis estimates suggested the influence of worry on both AN and anxiety disorders was independent of depressed affect. CONCLUSIONS: Overall our results provide mixed evidence regarding the causal role of anxiety exposures in AN aetiology. The inconsistency between outcomes of Studies One and Two may be explained by limitations surrounding worry assessment in Study One, confounding of the anxiety disorder and AN association in observational research, and low power in MR analyses probing causal effects of genetic liability to anxiety disorders. The evidence for worry acting as a causal risk factor for anxiety disorders and AN supports targeting worry for prevention of both outcomes. Further research should clarify how a tendency to worry translates into AN risk, and whether anxiety disorder pathology exerts any causal effect on AN.
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spelling pubmed-75423782020-10-08 Understanding the nature of association between anxiety phenotypes and anorexia nervosa: a triangulation approach Lloyd, E. Caitlin Sallis, Hannah M. Verplanken, Bas Haase, Anne M. Munafò, Marcus R. BMC Psychiatry Research Article BACKGROUND: Evidence from observational studies suggests an association between anxiety disorders and anorexia nervosa (AN), but causal inference is complicated by the potential for confounding in these studies. We triangulate evidence across a longitudinal study and a Mendelian randomization (MR) study, to evaluate whether there is support for anxiety disorder phenotypes exerting a causal effect on AN risk. METHODS: Study One assessed longitudinal associations of childhood worry and anxiety disorders with lifetime AN in the Avon Longitudinal Study of Parents and Children cohort. Study Two used two-sample MR to evaluate: causal effects of worry, and genetic liability to anxiety disorders, on AN risk; causal effects of genetic liability to AN on anxiety outcomes; and the causal influence of worry on anxiety disorder development. The independence of effects of worry, relative to depressed affect, on AN and anxiety disorder outcomes, was explored using multivariable MR. Analyses were completed using summary statistics from recent genome-wide association studies. RESULTS: Study One did not support an association between worry and subsequent AN, but there was strong evidence for anxiety disorders predicting increased risk of AN. Study Two outcomes supported worry causally increasing AN risk, but did not support a causal effect of anxiety disorders on AN development, or of AN on anxiety disorders/worry. Findings also indicated that worry causally influences anxiety disorder development. Multivariable analysis estimates suggested the influence of worry on both AN and anxiety disorders was independent of depressed affect. CONCLUSIONS: Overall our results provide mixed evidence regarding the causal role of anxiety exposures in AN aetiology. The inconsistency between outcomes of Studies One and Two may be explained by limitations surrounding worry assessment in Study One, confounding of the anxiety disorder and AN association in observational research, and low power in MR analyses probing causal effects of genetic liability to anxiety disorders. The evidence for worry acting as a causal risk factor for anxiety disorders and AN supports targeting worry for prevention of both outcomes. Further research should clarify how a tendency to worry translates into AN risk, and whether anxiety disorder pathology exerts any causal effect on AN. BioMed Central 2020-10-07 /pmc/articles/PMC7542378/ /pubmed/33028263 http://dx.doi.org/10.1186/s12888-020-02883-8 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Lloyd, E. Caitlin
Sallis, Hannah M.
Verplanken, Bas
Haase, Anne M.
Munafò, Marcus R.
Understanding the nature of association between anxiety phenotypes and anorexia nervosa: a triangulation approach
title Understanding the nature of association between anxiety phenotypes and anorexia nervosa: a triangulation approach
title_full Understanding the nature of association between anxiety phenotypes and anorexia nervosa: a triangulation approach
title_fullStr Understanding the nature of association between anxiety phenotypes and anorexia nervosa: a triangulation approach
title_full_unstemmed Understanding the nature of association between anxiety phenotypes and anorexia nervosa: a triangulation approach
title_short Understanding the nature of association between anxiety phenotypes and anorexia nervosa: a triangulation approach
title_sort understanding the nature of association between anxiety phenotypes and anorexia nervosa: a triangulation approach
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542378/
https://www.ncbi.nlm.nih.gov/pubmed/33028263
http://dx.doi.org/10.1186/s12888-020-02883-8
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