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Infections may increase risk for mental disorders, psychotropic use

Ole Köhler-Forsberg

Severe infections requiring hospitalization were linked to subsequent increased risk for hospitalization for any mental disorder and psychotropic medication use in Denmark, according to a nationwide cohort study published in JAMA Psychiatry.

Schizophrenia, obsessive-compulsive disorder, personality and behavior disorders, autism and ADHD were associated with the highest risks for hospitalization after infections, the findings suggest.

“Infections have been linked with the development of mental disorders,” Ole Köhler-Forsberg, MD, of Aarhus University Hospital in Denmark, told Healio.com/Psychiatry. “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.”

Using data from nationwide registers, researchers examined the link between all treated infections since birth and the later risk for any treated mental disorder through adolescence in Denmark. The investigators assessed data on all treated infections — including severe infections that required hospitalization and less severe infections treated with anti-infective agents in primary care settings — and on all mental disorders diagnosed in a hospital setting and any redeemed psychotropic drug prescription.

Analysis revealed a link between infections requiring hospitalizations and subsequent elevated risk for a diagnosis of any mental disorder (hazard rate ratio [HRR] = 1.84; 95% CI, 1.69-1.99). In addition, infections were associated with higher risk of redeeming a psychotropic drug prescription (HRR = 1.42; 95% CI, 1.37-1.46).

“These findings were more pronounced for the severe infections requiring hospitalization, but still the less severe infections treated with anti-infective agents increased the risk for mental disorders,” Köhler-Forsberg said.

Köhler-Forsberg and colleagues found that treating an infection with anti-infective agents was tied to increased risk for any mental disorder diagnosis (HRR = 1.4; 95% CI, 1.29-1.51) and of redeeming a psychotropic medication prescription (HRR = 1.22; 95% CI, 1.18-1.26). Antibiotic use was associated with an especially elevated risk.

“Our findings linking infections with mental disorders in the developing brain, despite several limitations that make causal links impossible, do add more knowledge to this growing field showing that there exists an intimate connection between the body and the brain,” Köhler-Forsberg said.

“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,” he continued. “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.”

The researchers found that the risk for mental disorders after infections rose in a dose-response association and with the temporal proximity of the last infection, with the highest risks seen immediately after the infection. Furthermore, risks remained elevated up to 10 years after the last treated infection, according to the results.

When examining the link between treated infections and specific mental disorder diagnoses, the researchers found that the risks were particularly high for:

• schizophrenia spectrum disorders;
• OCD;
• personality and behavior disorders;
• mental retardation;
• ASD;
• ADHD;
• oppositional defiant disorder and conduct disorder; and
• tic disorders.

“Future studies need to investigate in more detail whether and how specific infectious agents or the amount of infections can lead to mental disorders,” Köhler-Forsberg told Healio.com/Psychiatry. “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.”

There’s a possibility that the medications used to treat infections could be causing the observed effect, Viviane Labrie, PhD, and Lena Brundin, MD, PhD, of the Center for Neurodegenerative Sciences, Van Andel Research Institute, wrote in a related comment. They wrote that an important area for further research is examining the link between gut microbiome — which can be affected by antibiotics — and mental illness. – by Savannah Demko

Disclosure: The authors report no relevant financial disclosures. Brundin reports funding from the Michael J. Fox Foundation, NIH and VA. Labrie reports funding from the Alzheimer’s Society of Canada and the DoD.