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Children and teens living with idiopathic inflammatory myopathies (IIM)—including juvenile dermatomyositis (JDM)—often face more than muscle weakness, fatigue, and skin symptoms. Many also struggle with mental health challenges, such as anxiety and depression.
In 2025, Christian Lood, PhD, an Associate Professor at the University of Washington was awarded a grant through TMA’s Research Grants Program to study some of the things that go wrong in the bodies of children with JDM. Interestingly, one of the things he and his team discovered helps explain why these mental health challenges may happen and points toward possible new treatment options.
“Mental health challenges, including ‘brain fog,’ despite being a top priority for individuals with myositis, have historically not been a focus for the research community or the pharma companies given the challenges in quantifying it, and understanding its underlying biology,” Dr. Lood says. “Over the last decade, however, not least with the emergence of COVID-19 and subsequent long COVID, more emphasis has been put on understanding the link between our immune system and mental health in general.”
Dr. Lood and his team looked at how inflammation in JDM may change the body’s ability to process tryptophan, an essential nutrient found in foods like dairy, meat, and nuts. Tryptophan is important because the body uses it to make serotonin, a chemical that supports good mood and healthy sleep.
But inflammation—especially a type called type I interferon—can push tryptophan toward a different pathway that produces chemicals linked to stress, depression, and fatigue. This process is called the kynurenine pathway.
The study showed that kids with JDM had lower levels of tryptophan and serotonin compared to healthy children. Since serotonin plays a big role in mood and emotional balance, this might help explain why many children with JDM experience anxiety and depression.
Instead of becoming serotonin, more tryptophan was being converted into kynurenine and related metabolites (kynurenic acid and quinolinic acid). These chemicals were linked to higher inflammation, higher depression scores, and higher overall disease activity. This suggests that inflammation may directly affect mood—not just the physical burden of illness.
It appears that inflammation drives these changes. The researchers found that interferon, which is a powerful inflammatory signal, activates an enzyme called IDO, which diverts tryptophan away from serotonin and toward the kynurenine pathway.
Higher IDO activity was linked to lower serotonin levels and higher interferon activity. This creates a harmful cycle in which more inflammation leads to fewer “feel good” chemicals, which causes more symptoms of depression or anxiety.
“These findings are not specific for JDM, but similar processes seem to also contribute to depression in other inflammatory diseases, including lupus, arthritis, and COVID-19,” Dr. Lood says.
Some treatments, however, may help improve both physical and emotional symptoms related to inflammation and myositis. Two medications that block interferon—baricitinib and anifrolumab—were able to stop IDO activation in lab tests. Both of these medications are being tested as treatments for the inflammation of myositis, but in the process they may also normalize tryptophan processing and potentially improve mood symptoms. More research is needed, but this is a hopeful sign for future treatment options.
If you or your child lives with an inflammatory muscle disease, you may recognize the emotional challenges—feeling worried, sad, overwhelmed, or struggling with mood changes. This study shows these symptoms are not your fault, and they’re not “just in your head.” Your body’s inflammatory process may be affecting how your brain manages mood regulating chemicals. Treating that process will likely improve your mental health symptoms.
