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Association and familial co-aggregation of childhood-onset type 1 diabetes with depression, anxiety, and stress-related disorders: a population-based cohort study

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posted on 01.08.2022, 00:10 authored by Shengxin Liu, Marica Leone, Jonas F. Ludvigsson, Paul Lichtenstein, Brian D’Onofrio, Ann-Marie Svensson, Soffia Gudbjörnsdottir, Sarah E. Bergen, Henrik Larsson, Ralf Kuja-Halkola, Agnieszka Butwicka



To estimate the association and familial co-aggregation of childhood-onset type 1 diabetes with depression, anxiety, and stress-related disorders.

Research design and methods

Population-based cohort study using data from Swedish nationwide registers. A total of ~3.5 million individuals born in Sweden 1973-2007 were linked to their biological parents, full- and half-siblings, and cousins. Cox models were used to estimate the association and familial co-aggregation of type 1 diabetes with depression, anxiety, and stress-related disorders. 


Individuals diagnosed with childhood-onset type 1 diabetes (n=20,005) were found to be at greater risks of all outcomes: any psychiatric diagnosis (adjusted Hazard Ratio [aHR] [95% Confidence Intervals]: 1.66 [1.59-1.72]) or specific diagnoses of depression (1.85 [1.76-1.94]), anxiety (1.41[1.33-1.50]), stress-related disorders (1.75 [1.62-1.89]), as well as using antidepressants or anxiolytics (1.30 [1.26-1.34]), compared to individuals without type 1 diabetes. Overall, relatives of individuals with type 1 diabetes were at elevated risks of developing these outcomes, with the highest risks seen in parents (aHRs: 1.18-1.25), followed by full-siblings (aHRs: 1.05-1.20), and the magnitudes of risk estimates appear proportional to familial relatedness.


These results support existing evidence that children and adolescents with type 1 diabetes are at greater risks of developing depression, anxiety, and stress-related disorders and indicate that shared familial factors might contribute to these elevated risks. Our findings highlight the need for psychological consulting for children and their families in diabetes care. Quantitative and molecular genetic studies are warranted to further understand the etiology of these psychiatric disorders in type 1 diabetes. 


Financial support was provided through the Swedish Research Council (No 2017-00788) and Karolinska Institutet, Strategic Research Program in Neuroscience (StratNeuro). S.L. received a scholarship from the H.M. Queen Silvia’s Jubileumsfond for research on children with comorbid somatic and psychiatric disorders. A.B. was supported by Stockholm Region (clinical research appointment No 20180718) while working on this project. M.L. received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement no. 721567. The Swedish Twin Registry, managed by Karolinska Institutet, received funding through the Swedish Research Council grant (No 2017-00641).