Childhood-onset type 1 diabetes and subsequent adult psychiatric disorders: a nationwide cohort and genome-wide Mendelian randomization study.
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Childhood-onset type 1 diabetes (T1D) is associated with substantial psychiatric morbidity in later life, but it remains unknown whether these associations are due to common underlying biological mechanisms or the impacts of living with the condition and its treatment. Here, using Czech national register data, we identified children with T1D aged ≤14 years between 1994 and 2007 and estimated the risk of psychiatric disorders up to 24 years later. We found that children diagnosed with T1D had an elevated risk of developing substance use, mood, anxiety and personality disorders, and behavioral syndromes. Conversely, we found that children with T1D had a lower risk of developing psychotic disorders. In Mendelian randomization analysis, we found an association with schizophrenia, which, however, did not persist following multiple testing adjustment. The combined observational and Mendelian randomization evidence suggests that T1D diagnosis in childhood predisposes to far-reaching, extensive psychiatric morbidity, which is unlikely to be explicable by common underlying biological mechanisms. The findings of this study highlight that monitoring and addressing the mental health needs of children with T1D is imperative, whereas glucose dysregulation and/or inflammation implicated in schizophrenia pathogenesis warrants future research.
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Acknowledgements: This work was supported by the National Institute for Health and Care Research (NIHR), Applied Research Collaboration East of England, Cambridgeshire and Peterborough NHS Foundation Trust (T.F.), and the Ministry of Health, Czech Republic (00023752; T.F. and K.M.). S.B. is supported by the Wellcome Trust (225790/Z/22/Z) and the UK Research and Innovation Medical Research Council (MC_UU_00002/7). The funding organizations had no role in the design and conduct of the study; collection, management, analysis and interpretation of data; review or approval of the manuscript; or the decision to submit the manuscript for publication. The views expressed are those of the authors and not necessarily of the NIHR, the Department of Health and Social Care or other funders.
Funder: National Institute for Health Research, Applied Research Collaboration, East of England.
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2731-6076
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Wellcome Trust (225790/Z/22/Z)
MRC (MC_UU_00006/1)

