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. 2020 Sep:223:227-235.
doi: 10.1016/j.schres.2020.08.006. Epub 2020 Aug 19.

Common mechanisms for type 2 diabetes and psychosis: Findings from a prospective birth cohort

Benjamin I Perry  1 , Hannah J Jones  2 , Tom G Richardson  3 , Stan Zammit  4 , Nicholas J Wareham  5 , Glyn Lewis  6 , Peter B Jones  7 , Golam M Khandaker  7
Affiliations

Common mechanisms for type 2 diabetes and psychosis: Findings from a prospective birth cohort

Benjamin I Perry et al. Schizophr Res. 2020 Sep.

Abstract

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.

Keywords: ALSPAC; Diabetes mellitus; Polygenic risk; Psychosis; Schizophrenia.

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Conflict of interest statement

Declaration of competing interest The authors report no competing interests.

Figures

Fig. 1
Fig. 1
Prevalence of psychotic experiences and psychotic disorder at age 18 per tertile of PRS-T2DM.
Fig. 2
Fig. 2
Association between PRS score and outcome at age 18 years at different PRS P-value thresholds.
See this image and copyright information in PMC

References

    1. Andreassen O.A., Djurovic S., Thompson W.K., Schork A.J., Kendler K.S., O’Donovan M.C., Rujescu D., Werge T., van de Bunt M., Morris A.P., McCarthy M.I., International Consortium for Blood Pressure, G, Diabetes Genetics, R, Meta-analysis, C, Psychiatric Genomics Consortium Schizophrenia Working, G, Roddey J.C., McEvoy L.K., Desikan R.S., Dale A.M. Improved detection of common variants associated with schizophrenia by leveraging pleiotropy with cardiovascular-disease risk factors. Am. J. Hum. Genet. 2013;92(2):197–209. - PMC - PubMed
    1. Bahrami S., Steen N.E., Shadrin A., O’Connell K., Frei O., Bettella F., Wirgenes K.V., Krull F., Fan C.C., Dale A.M., Smeland O.B., Djurovic S., Andreassen O.A. Shared genetic loci between body mass index and major psychiatric disorders: a genome-wide association study. JAMA Psychiatry. 2020;77(5):503–512. - PMC - PubMed
    1. Boyd A., Golding J., Macleod J., Lawlor D.A., Fraser A., Henderson J., Molloy L., Ness A., Ring S., Davey Smith G. Cohort profile: the ‘Children of the 90s’–the index offspring of the Avon longitudinal study of parents and children. Int. J. Epidemiol. 2013;42(1):111–127. - PMC - PubMed
    1. Bulik-Sullivan B., Finucane H.K., Anttila V., Gusev A., Day F.R., Loh P.R., ReproGen, C, Psychiatric Genomics, C, Genetic Consortium for Anorexia Nervosa of the Wellcome Trust Case Control, C, Duncan L., Perry J.R., Patterson N., Robinson E.B., Daly M.J., Price A.L., Neale B.M. An atlas of genetic correlations across human diseases and traits. Nat. Genet. 2015;47(11):1236–1241. - PMC - PubMed
    1. Calabro P., Willerson J.T., Yeh E.T. Inflammatory cytokines stimulated C-reactive protein production by human coronary artery smooth muscle cells. Circulation. 2003;108(16):1930–1932. - PubMed

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