Köhler-Forsberg O, Petersen L, Gasse C, Mortensen PB,
Dalsgaard S, Yolken RH, Mors O, Benros ME. A Nationwide Study in Denmark of the
Association Between Treated Infections and the Subsequent Risk of Treated Mental
Disorders in Children and Adolescents. JAMA Psychiatry. 2018 Dec 5. doi:10.1001/jamapsychiatry.2018.3428. [Epub ahead of print]
Abstract
IMPORTANCE:
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.
OBJECTIVE:
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.
EXPOSURES:
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.
RESULTS:
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 adolescents.
______________________________________________________________________
Some prior research has also linked infections with the
development of mental disorders.
"However, no study has had the opportunity to
investigate this association between all treated infections (covering
hospitalizations and treatment with anti-infective agents) with the development
of any treated mental disorder within such a large cohort of 1.1 million
children and adolescents who were followed since birth," Kohler-Forsberg
noted…
Schizophrenia spectrum disorders, obsessive-compulsive
disorder, personality and behavior disorders, mental retardation, autism
spectrum disorder, attention-deficit/hyperactivity disorder, oppositional
defiant disorder, conduct disorder, and tic disorders were associated with the
highest risks following a severe infection.
The risk for a mental disorder after a severe infection
increased with the number of infections and with the temporal proximity of the
last infection. The biggest increase in risk was observed 0 to 3 months after
infection. Results of the primary analyses were supported by analyses that
included different reference groups and siblings…
"It therefore appears that infections and the inflammatory
reaction that follows afterwards can affect the brain and be part of the
process of developing severe mental disorders. This can, however, also be
explained by other causes, such as some people having a genetically higher risk
of suffering more infections and mental disorders," Kohler-Forsberg told
Medscape Medical News.
"Future studies need to investigate in more detail
whether and how specific infectious agents or the amount of infections can lead
to mental disorders. A better understanding of the role of infections and
antimicrobial therapy in the pathogenesis of mental disorders might lead to new
methods for the prevention and treatment of these devastating disorders,"
said Kohler-Forsberg…
Viviane Labrie, PhD, and Lena Brundin, MD, PhD, from the
Center for Neurodegenerative Sciences, Van Andel Research Institute, Grand
Rapids, Michigan, also say the results of the study leave a number of
"pressing questions.
"Since the study controlled for important confounders
and validated the findings in a sibling cohort, the results may reflect a
causative biological mechanism," they write, but "what could this
mechanism be? More importantly, could we reduce the incidence of debilitating
childhood neuropsychiatric disorders by targeting infection?"
"These results bring a sense of urgency to detailing
the underlying mechanisms of this association, in particular because of the
possibility that these severe and occasionally permanent neuropsychiatric
conditions might be rapidly recognized and treated by pharmacological compounds
already in clinical use," Labrie and Brundin conclude.
https://www.medscape.com/viewarticle/905999#vp_1
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