Lay Summary

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

Children with inflammatory bowel disease (IBD) have higher rates of depression than healthy children.  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 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 will recruit 60 children with IBD (aged 7 – 17 years) and follow them to study the relationship between disease activity, proinflammatory cytokines, HPA axis functioning (cortisol), and depression.  We will assess the children with IBD at diagnosis before they start any corticosteroids and 6 month after any steroid treatment when their disease is in remission.  We expect that when the disease is active, children with IBD will 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.  However, our preliminary 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 expect that increases in proinflammatory cytokines will be associated with increases in cytokine-related depression symptoms.

This research will investigate relationships between immunity/inflammation and depression in children with IBD.  It is particularly significant because immunity and depression affect each other. Therefore, these results may lead to improved prevention and intervention of depression symptoms, but more importantly, they may lead to improved treatment of IBD by treating depression.  If the immune/inflammatory system in children with IBD contributes to depression symptoms, then interventions that affect this system should be targeted as interventions for depression in this population.  For example, stress coping and relaxation interventions have been found to have effects on immune function and may be particularly beneficial in addressing depression in this population.  Additionally, since these relationships go both ways, stress coping and relaxation interventions may have positive effects on disease activity as well.  Medications that alter the immune system should also be investigated for their positive effect on depression. Similarly, antidepressant medications could be investigated for any effects on disease activity, since both cytokine levels and HPA axis functioning improve in depressed individuals when they are given antidepressants. Some antidepressants may be better at altering the immune system than others, so this is another avenue of investigation. This study is a critical first step in determining these relationships.