A Nationwide Study in Denmark of the Association Between Treated Infections and the Subsequent Risk of Treated Mental Disorders in Children and Adolescents | Adolescent Medicine | JAMA Psychiatry | JAMA Network

Infections have been associated with increased risks for
mental disorders, such as schizophrenia and depression. However, the
association between all infections requiring treatment and the wide
range of mental disorders is unknown to date.

To investigate the association between all treated infections
since birth and the subsequent risk of development of any treated mental
disorder during childhood and adolescence.

Design, Setting, and Participants
Population-based cohort study using Danish nationwide
registers. Participants were all individuals born in Denmark between
January 1, 1995, and June 30, 2012 (N = 1 098 930). Dates of analysis
were November 2017 to February 2018.

All treated infections were identified in a time-varying
manner from birth until June 30, 2013, including severe infections
requiring hospitalizations and less severe infection treated with
anti-infective agents in the primary care sector.

Main Outcomes and Measures
This study identified all mental disorders diagnosed in a
hospital setting and any redeemed prescription for psychotropic
medication. Cox proportional hazards regression was performed reporting
hazard rate ratios (HRRs), including 95% CIs, adjusted for age, sex,
somatic comorbidity, parental education, and parental mental disorders.

A total of 1 098 930 individuals (51.3% male) were followed up
for 9 620 807.7 person-years until a mean (SD) age of 9.76 (4.91)
years. Infections requiring hospitalizations were associated with
subsequent increased risk of having a diagnosis of any mental disorder
(n = 42 462) by an HRR of 1.84 (95% CI, 1.69-1.99) and with increased
risk of redeeming a prescription for psychotropic medication
(n = 56 847) by an HRR of 1.42 (95% CI, 1.37-1.46). Infection treated
with anti-infective agents was associated with increased risk of having a
diagnosis of any mental disorder (HRR, 1.40; 95% CI, 1.29-1.51) and
with increased risk of redeeming a prescription for psychotropic
medication (HRR, 1.22; 95% CI, 1.18-1.26). Antibiotic use was associated
with particularly increased risk estimates. The risk of mental
disorders after infections increased in a dose-response association and
with the temporal proximity of the last infection. In particular,
schizophrenia spectrum disorders, obsessive-compulsive disorder,
personality and behavior disorders, mental retardation, autistic
spectrum disorder, attention-deficit/hyperactivity disorder,
oppositional defiant disorder and conduct disorder, and tic disorders
were associated with the highest risks after infections.

Conclusions and Relevance
Although the results cannot prove causality, these findings
provide evidence for the involvement of infections and the immune system
in the etiology of a wide range of mental disorders in children and

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