Understanding and Treating Neuropsychiatric Symptoms of Pediatric Physical Illness
Understanding and Treating Neuropsychiatric Symptoms of Pediatric Physical Illness
This research will examine the impact of brain activity, cognitive processing immune
 functioning, and gastrointestinal functioning on depressive symptoms and response to a
 psychotherapeutic intervention in youths with Inflammatory Bowel Disease (IBD).
Depression is costly, worsens morbidity and mortality, and has detrimental effects on disease
 course in physically ill populations. This research takes a novel multi-dimensional approach
 to assess the neurobiological basis of depression in chronic pediatric physical illness using
 inflammatory bowel disease (IBD) as a model. It also evaluates the efficacy of a modified
 cognitive behavioral therapy (CBT) on emotional well-being, physical health, economic costs,
 and neurobiological outcomes. These results will provide key building blocks for a paradigm
 shift within medicine by integrating behavioral health into the comprehensive medical care of
 physical illnesses.

 Little is known about how the brain and body interact to increase depressive vulnerability,
 particularly in youth. Adult studies identify disruptions in limbic and prefrontal brain
 activity in the pathophysiology of depression. Cytokines secondary to inflammation and
 exogenous treatment with steroids can cause mood and cognitive changes in these same brain
 regions. It is important to understand the neuropsychiatric effects of IBD and its treatment
 on underlying brain structures during adolescence, a critical developmental period for brain
 maturation underlying emotional regulation and cognitive processing. More importantly,
 neuronal plasticity during adolescence may still allow reversibility of disease-related brain
 effects through teaching coping strategies for life-long illness management that could change
 developmental trajectories and reduce vulnerability in adulthood.

 Using translational neuroscience approaches, this research will examine: 1) brain regions
 that underlie emotional and cognitive processing in youth with active IBD and depression
 using brain functional magnetic resonance imaging compared to youth with IBD and no
 depression, and normal controls; 2) the inter-relationship between depressive symptoms in IBD
 and brain, immune, and gastrointestinal functioning; and 3) efficacy of a combined
 CBT-physical illness narrative intervention targeting emotional and cognitive processing
 compared to supportive non-directive therapy in the depressed IBD cohort with longitudinal
 tracking of emotional, physical health, economic, and neurobiological outcomes.
Inclusion criteria for youths with IBD for Step 1 of Screening Process:

 -  Age 12 to 17 inclusive

 -  English-speaking

 -  Capable of completing CDI

 -  Meeting diagnostic criteria for IBD

 -  Absence of mental retardation by history

 -  Having at least one appointment at the GI clinic.

 Criteria for Classification of IBD:

 1. Presence of appropriate history: abdominal pain, chronic diarrhea, bloody diarrhea
 (with or without extraintestinal symptoms) or, less commonly, a) primary
 extraintestinal symptoms, b) growth retardation, c) perirectal abscess, or d) acute
 abdomen.

 2. Evidence of colitis, ileitis or granulomatous esophagitis, gastritis or duodenitis by
 biopsy and/or small bowel strictures or fistulas by X-ray or multiple small intestinal
 ulcerations by capsule endoscopy.

 Eligibility Criteria For youths with IBD for Intervention Phase of the Comparison Study

 Inclusion Criteria:

 1. CDI or CDI-P > 10 at Step 1

 2. Childhood Depression Rating Scale-revised (CDRS-R) > 34 at Step 2

 3. Presence of at least one biological parent. Exclusion Criteria

 1. History or current episode of bipolar disorder, eating disorder, or psychotic disorder
 by Diagnostic and Statistical Manual (DSM)-IV criteria. 2. Recent suicide attempt (within 1
 month of study entry) or depression severity requiring acute psychiatric hospitalization
 within 3 months of study entry. 3. Antidepressant medications within one month of
 assessment. 4. Substance abuse by history within 1 month of study entry. 5. Current
 treatment with CBT or failure of previous CBT trial for depression judged adequate by at
 least 12 treatment sessions over a period of less than 1 year conducted by an appropriately
 trained mental health provider using a manual. If currently receiving other psychotherapy
 modalities, willingness to suspend treatment for 12-week acute treatment phase of study.

 Physically Healthy Comparison Children

 Inclusion Criteria:

 -  Age 12 to 17 inclusive

 -  English-speaking

 -  Capable of completing CDI

 -  Absence of mental retardation by history

 Exclusion Criteria:

 -  self-report of a cold, flu or other infection within the past two weeks

 -  self-reported use of any antibiotics within the past 2 weeks

 -  score of 6 or more on the blood draw screening questionnaire

 Screening process for youths with IBD: Participants will be recruited from the clinic
 through a 2-step screening of all consecutive pediatric patients seen in the IBD clinic or
 while medically hospitalized for an IBD flare-up at Children's Hospital of Pittsburgh, who
 have confirmed IBD and who meet the other eligibility criteria as determined by medical
 staff in IBD clinic (Tables 5 and 6). The medical diagnosis of IBD will be determined by a
 GI physician using criteria below and will be confirmed in the medical record. Step 1:
 administration of the CDI and CDI-P during the medical visit. Those subjects whose CDI
 and/or CDI-P score of > 10 will be invited by phone to participate in Step 2: a face to
 face interview. Step 2 assessment will be conducted within one week of Step 1 so that both
 CDI score and IBD severity ratings are still valid from the Step 1 screen.

 All subjects meeting eligibility criteria for Step 2 will be invited to participate in the
 completion of neuropsychiatric questionnaires, blood draw, pupil measurements, and brain
 functional magnetic resonance imaging.

 All subjects meeting eligibility criteria after Step 2 will be invited to participate in
 the treatment phase of the study.

 Normal controls (N=15) will be recruited from the Department of Pediatrics during
 outpatient clinical office visits.