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Researchers have identified a link between some infections and mental illnesses such as schizophrenia, depression and bipolar disorder. New research from Denmark confirms this connection. The study by JAMA Psychiatry published on Thursday shows that a variety of infections, even more common, such as bronchitis, are associated with a higher risk of many mental illnesses in children and adolescents.
The findings support the notion that infections affect mental health, possibly by affecting the immune system.
"This notion that the activation of the body's immune system plays a role as a triggering factor in … certain mental illnesses has really become established," says Dr. Roger McIntyre, Professor of Psychology and Pharmacology at the University of Toronto, who was not involved in the study. "This study complements this in general, but builds the case in a convincing manner."
In the new study, researchers collected data on hospitalization and prescription drugs for the 1.1 million children born between January 1, 1995 and June 30, 2012 in Denmark.
"We could track individuals from birth, so there was no information missing during their studies," says Dr. Ole Köhler-Forsberg from the University Hospital Aarhus, a neuroscientist and one of the authors of the study.
Köhler-Forsberg and his colleagues used two national registries to obtain data on hospitalizations for severe infections such as pneumonia, and data on antimicrobial or antiparasitic drugs prescribed to children for less severe infections. "Most of them are the infections that you and I and all the others have experienced," says Köhler-Forsberg.
While the majority of children in the sample suffered from infections, only a small proportion of them were diagnosed with any type of mental illness. About 4 percent have diagnosed disorders such as schizophrenia, attention deficit hyperactivity disorder, anxiety and personality disorders. Overall, 5.2 percent were prescribed drugs for mental disorders.
In all mental illnesses, with the exception of depression and bipolar disorder, the team found that hospitalization for an infection was associated with an 84 percent higher risk of being diagnosed with a mental disorder in a hospital 42 percent increased risk of being prescribed a drug for mental illness.
Less severe infections treated with antibiotic, antiviral, antifungal or antiparasitic drugs were associated with a 40 percent higher risk of mental illness diagnosis in a hospital and a 22 percent higher risk of getting a prescription.
However, the increased risk of mental illness after infection was less dramatic when the authors performed additional analysis on the influence of genetics and the home environment. The authors compared the results of more than 800,000 siblings in this population – siblings who had infections with those who did not. In this analysis, they found that the increased risk of mental illness after hospitalization dropped to 21 percent (from 84 percent). Similarly, the risk of receiving a psychotropic drug after hospitalization dropped to 17 percent.
However, the risk had not fallen to zero, notes Köhler-Forsberg. "This is another finding that has made us more confident that there is a link between infections or the immune system and mental disorders," he says.
The authors also found that the risk of mental disorder was highest within the first three months of infection.
"And we also found out that the more infections and the heavier the infections, the higher the risk," says Köhler-Forsberg. "So there is this burden of infection that affects the brain and mental disorders."
Previous studies have also shown a link between infections and mental illness, says McIntyre. For example, a 2013 study of some members of the current research team showed that hospital stays due to autoimmune diseases and infections were associated with an increased risk of mood disorders such as depression and bipolar disorder in adults.
Similarly, influenza in pregnant women has been associated with an increased risk of schizophrenia in their children. Other studies have shown that other infections are also associated with schizophrenia.
However, the mechanism underlying the compound is not yet fully understood. A theory supported by several studies suggests that infections contribute to mental illness by activating the body's own inflammatory response.
A subgroup of people with various mental illnesses, from schizophrenia and depression to autism and bipolar disorder, has a "proinflammatory balance," says McIntyre. In other words, their bodies are in a state of inflammation.
"Thus, the naturally occurring proinflammatory proteins are higher and naturally occurring anti-inflammatory proteins, which we also produce, are relatively low," he says. "The rocker is thus adjusted to an inflammatory condition."
"What we have been struggling with for a long time is … does it [inflammation] cause mental illness or is it a consequence of mental illness?" says McIntyre. The new study suggests that this is the former, as the researchers were able to show that the diagnosis of mental illness occurred shortly after the infection.
"At least from a temporal perspective, activation of the inflammatory system came first, followed by mental illness," he says. "This gives the idea that the inflammatory immune system is the cause, less weight than a consequence of a mental illness."
However, inflammation is not the only way to influence mental health. In some cases, pathogens could be the culprits, says Köhler-Forsberg.
"Some infections start as a peripheral infection in the body and can cross the blood-brain barrier and enter the brain, causing damage and increasing the risk of mental disorders," he says.
A well-known example is a parasite called Toxoplasma gondii, which spreads, inter alia, through contact with contaminated cat feces.
It is unlikely that this pathogen was involved in the cases of this new study, Dr. Lena Brundin, a professor at the Van Andel Research Institute in Grand Rapids, Michigan, who authored an accompanying editorial to the new study. However, she says, "We know that the parasite can go to the brain and later be associated with some psychiatric symptoms."
"We have seen that patients with Toxoplasma gondii can be more suicidal," she adds.
The parasite influences brain function, including dopamine production, says Brundin. "It can also cause localized inflammation in the brain."
It is also known that the herpes virus passes the blood-brain barrier and slumbers in the neurons and is reactivated years later.
Another way in which infections or the treatment of an infection can affect mental health could be the alteration of the intestinal microbiome, the authors of the new study write. "It's very difficult to say why or why because we do not understand how microbiomes work," says Köhler-Forsberg.
It is also known that some antibiotics enter the brain, McIntyre notes, so they could also have direct effects. The new study found that antibiotics were associated with the highest risk of later diagnosis of mental illness from any medication given to infants for their infections. A "reasonable use of antibiotics" could reduce this risk, he says.
Regarding parents, McIntyre, Brundin and Köhler-Forsberg point out that the results do not mean that every child who develops an infection becomes mentally ill.
"You should be reassured that the great majority of these children will not get mental illness," says McIntyre. Finally, infections are necessary for the normal development of the immune system.
That is, parents should look for signs of anxiety, behavioral problems or other potential symptoms of mental illness after infection, Köhler-Forsberg notes. If they notice something in their child, they should seek help immediately, he adds.
"If a child is so unhappy to develop mental health problems, then we know that [in most cases]when it is detected early and treated well, will make the child better again," he says.