Scientific Abstract

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

Youth with inflammatory bowel disease (IBD) are at significant risk for depression.  However, little is known about the role of the inflammation in depression in pediatric IBD.  Two mechanisms may contribute to the development of depression in IBD:  proinflammatory cytokines and a hypoactive HPA axis.  Proinflammatory cytokines mediate inflammation and induce illness behaviors that mimic symptoms of depression.  Individuals with inflammatory diseases also have hyporeactive HPA axes that fail to appropriately rein in the inflammatory process via cortisol.  The hyporeactive HPA axis cannot respond appropriately to immune challenges or psychosocial stress, which may lead to vulnerability to both disease flares and depression symptoms.  Our goal is to improve the adjustment of children with IBD by determining the relationships between inflammation, HPA axis, and depression.

We will recruit 60 children with IBD (aged 7 – 17 years) and follow them longitudinally to study the relationship between disease activity, proinflammatory cytokines, HPA axis functioning (cortisol), and depressive symptoms.  Assessments of the children with IBD will occur at diagnosis prior to initiation of any corticosteroid treatment and 6 months post-steroid treatment when the disease is in remission.  We expect that when the disease is active, children with IBD will have increased proinflammatory cytokine levels, attenuated HPA axis functioning, and increased depression symptoms.  When the disease is in remission, previous research suggests that children with IBD continue to be at risk for depression.  Our preliminary results suggest that there may be a shift in the specific symptoms that are endorsed, so that fewer cytokine-related symptoms are endorsed, and more “psychological” symptoms (e.g., hopelessness) are reported.  Throughout the disease course, we expect that increases in proinflammatory cytokines will be directly associated with increases in cytokine-related depression symptoms, as well as indirectly related to depression symptoms via an association with blunted HPA axis reactivity.

This research will investigate the relationships between immunity and depression in children with a chronic illness.  It is significant because relationships between immunity and depression are bidirectional. As such, new information may be obtained that will lead to improved prevention and intervention in the area of depression, but more importantly, the information may lead to improved treatment of IBD via the treatment of depression. If the immune/inflammatory system in children with IBD contributes to depression symptoms, then interventions that alter this system should be investigated as targeted 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, given the bidirectionality of these relationships, stress coping and relaxation interventions can be investigated for their effects on disease activity. Medications that alter the immune system should also be investigated for their effect on depressive symptoms. 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 given antidepressants. Some antidepressants may prove more efficacious in altering the immune system than others, so this is another avenue of investigation. This proof of concept study is a critical first step in determining these relationships.