Final Progress Report
Proposal No. IBD-0231R
Principal Investigator: Laura Mackner, Ph.D.
Applicant Organization: The Research Institute at Nationwide Children's Hospital (Columbus, Ohio, U.S.A.)
Project Title: Depression, cytokines, and cortisol in pediatric inflammatory bowel disease
Period of Award: June 1, 2008 – May 31, 2010
LAY SUMMARY
Children with IBD have higher rates of depression than healthy children, and aspects of their disease may put them at risk for depression. In particular, the inflammation associated with IBD may give rise not only to the symptoms of IBD but also to depression symptoms. Two aspects of the process of inflammation may contribute to depression in IBD: proinflammatory cytokines and the hypothalamic-pituitary-adrenal (HPA) axis in the brain. Cytokines play a large role in causing inflammation, and they also cause “illness behaviors” that are the same as some symptoms of depression. The HPA axis works to keep inflammation in check, but people with inflammatory diseases such as IBD have poorly functioning HPA axes that do not react appropriately rein in the inflammation. The dysfunctional HPA axis cannot respond appropriately to immune challenges or to psychosocial stress, which may make an individual vulnerable to a disease flare and/or depression symptoms. In addition, both disease flares and psychosocial stress can lead to depression. Our goal is to improve the psychosocial adjustment of children with IBD by determining the relationships between inflammation, HPA axis functioning, and depression symptoms.
We recruited 12 children with IBD (aged 7 – 17 years) and followed them to study the relationship between disease activity, proinflammatory cytokines, HPA axis functioning (cortisol), and depression symptoms. We assessed the children with IBD at diagnosis before they started any corticosteroids. We assessed 6 of them 3 months after steroid treatment when their disease was in remission. We expected that when the disease was active, children with IBD would have more proinflammatory cytokines, worse HPA axis functioning, and more depression symptoms. When the disease is in remission, previous research suggests that children with IBD continue to be at risk for depression symptoms. However, our previous results suggest that there may be a shift in the specific symptoms that these children experience, so that they have fewer cytokine-related symptoms, and more “psychological” symptoms (e.g., hopelessness). Throughout the disease course, we expected that increases in proinflammatory cytokines would be associated with increases in cytokine-related depression symptoms.
Our results suggest that children with IBD have dysfunctional HPA axes. It is unclear how HPA axis function is related to disease activity: for one task, it appeared worse when the children were in remission, but in another task, it appeared worse when their disease was active. Levels of a proinflammatory cytokine were associated with worse depression symptoms, especially the cytokine-related symptoms we expected to see. Cytokine levels were also associated with HPA axis function. Additional research would be needed to fully examine the rest of our hypotheses.