Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Perry, Benjamin I., Jones, Hannah J., Richardson, Tom G., Zammit, Stan, Wareham, Nicholas J., Lewis, Glyn, Jones, Peter B., Khandaker, Golam M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Science Publisher B. V 2020
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
_version_ 1783627009689124864
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
work_keys_str_mv AT perrybenjamini commonmechanismsfortype2diabetesandpsychosisfindingsfromaprospectivebirthcohort
AT joneshannahj commonmechanismsfortype2diabetesandpsychosisfindingsfromaprospectivebirthcohort
AT richardsontomg commonmechanismsfortype2diabetesandpsychosisfindingsfromaprospectivebirthcohort
AT zammitstan commonmechanismsfortype2diabetesandpsychosisfindingsfromaprospectivebirthcohort
AT warehamnicholasj commonmechanismsfortype2diabetesandpsychosisfindingsfromaprospectivebirthcohort
AT lewisglyn commonmechanismsfortype2diabetesandpsychosisfindingsfromaprospectivebirthcohort
AT jonespeterb commonmechanismsfortype2diabetesandpsychosisfindingsfromaprospectivebirthcohort
AT khandakergolamm commonmechanismsfortype2diabetesandpsychosisfindingsfromaprospectivebirthcohort