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Common mechanisms for type 2 diabetes and psychosis: Findings from a prospective birth cohort
BACKGROUND: Psychosis and type 2 diabetes mellitus (T2DM) are commonly comorbid and may share pathophysiologic mechanisms. To investigate shared genetic variation and inflammation as potential common mechanisms, we tested: (i) associations between genetic predisposition for T2DM and psychotic experi...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Science Publisher B. V
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758839/ https://www.ncbi.nlm.nih.gov/pubmed/32828613 http://dx.doi.org/10.1016/j.schres.2020.08.006 |
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author | Perry, Benjamin I. Jones, Hannah J. Richardson, Tom G. Zammit, Stan Wareham, Nicholas J. Lewis, Glyn Jones, Peter B. Khandaker, Golam M. |
author_facet | Perry, Benjamin I. Jones, Hannah J. Richardson, Tom G. Zammit, Stan Wareham, Nicholas J. Lewis, Glyn Jones, Peter B. Khandaker, Golam M. |
author_sort | Perry, Benjamin I. |
collection | PubMed |
description | BACKGROUND: Psychosis and type 2 diabetes mellitus (T2DM) are commonly comorbid and may share pathophysiologic mechanisms. To investigate shared genetic variation and inflammation as potential common mechanisms, we tested: (i) associations between genetic predisposition for T2DM and psychotic experiences and psychotic disorder in young adults; (ii) the association between genetic predisposition for schizophrenia and insulin resistance (IR), a precursor of T2DM; and (iii) whether these associations are mediated by childhood inflammation. METHODS: Psychotic experiences (PEs), psychotic disorder and IR were assessed at age 18. Polygenic risk scores (PRS) for T2DM and schizophrenia were derived based on large genome-wide association studies. Associations between PRS and psychotic/IR outcomes were assessed using regression analysis based on 3768 ALSPAC birth cohort participants with complete data. Inflammatory markers C-reactive protein (CRP) and interleukin 6 (IL-6) measured at age 9 were used in regression and mediation analyses. RESULTS: Genetic predisposition for T2DM was associated with PEs (adjusted OR = 1.21; 95% CI, 1.01–1.45) and psychotic disorder (adjusted OR = 1.51; 95% CI, 1.04–2.03) at age 18 in a linear dose-response fashion. Genetic predisposition for schizophrenia was weakly associated with IR (adjusted OR = 1.10; 95% C·I, 0.99–1.22) at age 18. The association between genetic risk for T2DM and PEs was partly mediated by childhood CRP (p = .040). CONCLUSIONS: Comorbidity between psychosis and T2DM may be partly underpinned by shared genes and inflammation. A summation of minor genetic variation representing lifetime risk for T2DM at conception may predispose individuals to psychosis in adulthood by influencing physiologic changes, such as low-grade inflammation, detectable as early as childhood. |
format | Online Article Text |
id | pubmed-7758839 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier Science Publisher B. V |
record_format | MEDLINE/PubMed |
spelling | pubmed-77588392020-12-28 Common mechanisms for type 2 diabetes and psychosis: Findings from a prospective birth cohort Perry, Benjamin I. Jones, Hannah J. Richardson, Tom G. Zammit, Stan Wareham, Nicholas J. Lewis, Glyn Jones, Peter B. Khandaker, Golam M. Schizophr Res Article BACKGROUND: Psychosis and type 2 diabetes mellitus (T2DM) are commonly comorbid and may share pathophysiologic mechanisms. To investigate shared genetic variation and inflammation as potential common mechanisms, we tested: (i) associations between genetic predisposition for T2DM and psychotic experiences and psychotic disorder in young adults; (ii) the association between genetic predisposition for schizophrenia and insulin resistance (IR), a precursor of T2DM; and (iii) whether these associations are mediated by childhood inflammation. METHODS: Psychotic experiences (PEs), psychotic disorder and IR were assessed at age 18. Polygenic risk scores (PRS) for T2DM and schizophrenia were derived based on large genome-wide association studies. Associations between PRS and psychotic/IR outcomes were assessed using regression analysis based on 3768 ALSPAC birth cohort participants with complete data. Inflammatory markers C-reactive protein (CRP) and interleukin 6 (IL-6) measured at age 9 were used in regression and mediation analyses. RESULTS: Genetic predisposition for T2DM was associated with PEs (adjusted OR = 1.21; 95% CI, 1.01–1.45) and psychotic disorder (adjusted OR = 1.51; 95% CI, 1.04–2.03) at age 18 in a linear dose-response fashion. Genetic predisposition for schizophrenia was weakly associated with IR (adjusted OR = 1.10; 95% C·I, 0.99–1.22) at age 18. The association between genetic risk for T2DM and PEs was partly mediated by childhood CRP (p = .040). CONCLUSIONS: Comorbidity between psychosis and T2DM may be partly underpinned by shared genes and inflammation. A summation of minor genetic variation representing lifetime risk for T2DM at conception may predispose individuals to psychosis in adulthood by influencing physiologic changes, such as low-grade inflammation, detectable as early as childhood. Elsevier Science Publisher B. V 2020-09 /pmc/articles/PMC7758839/ /pubmed/32828613 http://dx.doi.org/10.1016/j.schres.2020.08.006 Text en © 2020 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Perry, Benjamin I. Jones, Hannah J. Richardson, Tom G. Zammit, Stan Wareham, Nicholas J. Lewis, Glyn Jones, Peter B. Khandaker, Golam M. Common mechanisms for type 2 diabetes and psychosis: Findings from a prospective birth cohort |
title | Common mechanisms for type 2 diabetes and psychosis: Findings from a prospective birth cohort |
title_full | Common mechanisms for type 2 diabetes and psychosis: Findings from a prospective birth cohort |
title_fullStr | Common mechanisms for type 2 diabetes and psychosis: Findings from a prospective birth cohort |
title_full_unstemmed | Common mechanisms for type 2 diabetes and psychosis: Findings from a prospective birth cohort |
title_short | Common mechanisms for type 2 diabetes and psychosis: Findings from a prospective birth cohort |
title_sort | common mechanisms for type 2 diabetes and psychosis: findings from a prospective birth cohort |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758839/ https://www.ncbi.nlm.nih.gov/pubmed/32828613 http://dx.doi.org/10.1016/j.schres.2020.08.006 |
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