To Örebro University

Background and aims: People with type 1 diabetes are known to be at heightened risk of common mental health problems. However, it remains unknown whether genetic liability contributes to the elevated risk. This study aimed to investigate the association and familial co-aggregation of type 1 diabetes with depression, anxiety and stress-related disorders.

Materials and methods: Using multiple Swedish nationwide registers, we obtained a population sample of individuals born 1973-2007 and still residing in Sweden at age 5. Individuals were linked to their biological parents, full-siblings, half-siblings, full-cousins and half-cousins. We obtained information from the National Patient Register (since 1973) on the diagnoses of type 1 diabetes, depression, anxiety and stress-related disorders using ICD codes and from the Prescribed Drug Register (since 2005) on the prescribed antidepressants and anxiolytics using ATC codes. Primary outcomes were any or specific diagnosis of 1) depression, 2) anxiety and 3) stress-related disorders. We examined a secondary outcome of using antidepressants or anxiolytics in those who resided in Sweden after 2005.

Results: In this cohort study of about 3.5 million individuals, 20005 (53.9% male) were diagnosed with childhood-onset type 1 diabetes (< 18 years of age, the median age at onset: 9.7). We used Cox models to estimate the association between type 1 diabetes and each outcome. Individuals were regarded as unexposed before diagnosis and exposed after. During a median follow-up of 22.2 years, individuals with type 1 diabetes were at a higher risk of all outcomes after adjusting for sex and birth year: any diagnosis (HR [95%CI]: 1.73 [1.67-1.80]), depression (1.93 [1.84-2.02]), anxiety (1.41[1.33-1.50]), stress-related disorders (1.75 [1.62-1.89]) and using antidepressants or anxiolytics (1.30 [1.26-1.34]). Familial co-aggregation was evaluated using Cox models, where an individual’s relative was regarded unexposed before the individual’s diabetes diagnosis and exposed after. Overall, higher risks of all outcomes were observed in relatives of individuals with diabetes and declined proportionally with decreasing genetic relatedness. Highest HRs were found in parents: any diagnosis (1.21 [1.16, 1.26]), depression (1.20 [1.13-1.26]), anxiety (1.22 [1.15, 1.30]), stress-related disorders (1.25 [1.17-1.34]) and using antidepressants or anxiolytics (1.18 [1.16, 1.21]). HRs decreased but remained significant in full-siblings after adjusting for sex and birth year of the sibling: any diagnosis (1.11 [1.05, 1.17]), depression (1.11 [1.03-1.19]), anxiety (1.10 [1.02, 1.1]), stress-related disorders (1.20 [1.08-1.32]) and using antidepressants or anxiolytics (1.05 [1.01, 1.09]). HRs decreased and were not significant in maternal and paternal half-siblings (HRs 0.90-1.10; 1.00-1.11), full-cousins (HRs 0.98-1.05) and half-cousins (HRs 0.80-1.02).

Conclusion: Our findings support existing evidence that individuals with childhood-onset type 1 diabetes were at higher risks of depression, anxiety, stress-related disorders and using antidepressants and anxiolytics and suggest that familial liability may contribute to these associations. The results highlight the importance of family support integrated with pediatric diabetes care.