ORLANDO, Fla. — Two studies presented at the Advances in IBD meeting showed the potential neurological and psychological implications of pediatric Crohn’s disease and the treatment thereof, with these patients showing cortical thinning and more school problems than healthy counterparts.
“The potential adverse effects of disease and treatment on brain and cognitive function carry clinical implications for the development of our young patients, particularly in the setting of recurring illness and increasingly younger ages of disease onset,” Christine Mrakotsky, PhD, assistant professor of psychology at Harvard Medical School, said during her presentation. “In short, we have to identify the patients that are at the highest risk for these cognitive brain outcomes early and begin appropriate interventions.”
In the first study, Mrakotsky and colleagues conducted baseline brain MRIs, cognitive assessment and bloodwork followed by cognitive assessment and bloodwork after 6 months, in which patients with active Crohn’s disease received steroids for treatment.
The study looked at 12 patients with Crohn’s disease, during an acute flare and later on steroids compared to 20 age-matched healthy controls between the ages of 9 and 14 years. Active disease patients and controls were similar in sex, ethnicity, income, IQ, experienced pain and reported sleep problems.
As expected, inflammatory markers (Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)] were higher in Crohn’s patients compared to healthy controls (ESR P=.006; CRP P=.051).
After adjusting for age and sex and correcting for multiple comparisons, Mrakotsky found cortical thickness to be significantly thinner in the Crohn’s disease group when compared to healthy controls in widespread regions of the brain (P<.001-.01). Reduced thickness correlated with higher steroid dose, greater inflammation and worse school function at baseline, as well as poorer cognitive function at 6 month retest, she said.
“Steroid therapy was the most robust predictor for cortical thinning,” Mrakotsky said. “Both inflammation and steroid treatment are associated with cortical thinning, particularly in frontal and posterior temporal brain regions. These cortical regions play a critical role in higher cognitive and emotional processes and are potentially linked to previously reported poorer emotional and school functioning in this population. We also believe IBD-related brain differences have the potential to affect cognitive and emotional development long-term.”
Cognitive, psychological impact
In another study looking at 85 children with Crohn’s disease (active and in remission) and 37 healthy controls aged 8 to 17 years, Mrakotsky and colleagues assessed the rate of school problems experienced by the patients. They obtained school and medical history, cognitive assessment and serum inflammation. Similarly to the first study, assessments were completed at baseline and again at 6 months.
“Our Crohn’s patients as a whole — both inactive and active — showed poorer cognitive function than healthy controls,” she said.
On cognitive assessments, participants with Crohn’s disease demonstrated poorer general cognitive function, particularly in nonverbal IQ, Mrakotsky showed. When looking at memory function, children with Crohn’s disease, both active and in remission, showed significantly or trending poorer verbal (word lists) and nonverbal (spatial location, geometric figures) memory.
Children with Crohn’s disease also reported higher rates of school problems than their healthy counterparts in the following areas: reported school problems (23.5% vs. 8.1%, P=.048); placement on educational plans (38.8% vs. 0%, P=.00); and educational interventions (45.9% vs. 2.7%, P=.00).
“While these results are still tentative, school function does correlate with cortical thickness and other brain variables,” Mrakotsky said. “While we don’t know the underlying neurobiological mechanisms quite yet, these findings carry implications for clinical recommendations for routine neuropsychological and psychological screening. If we do identify problems on these screenings, then we can argue for educational and psychological interventions in addition to medical therapies, which could include provision of special educational services … and targeted therapy for emotional problems.”
For more information:
Mrakotsky C. O-010; O-013. Presented at: 2014 Advances in Inflammatory Bowel Diseases, Dec. 4-6, 2014; Orlando, Fla.
Disclosures: Mrakotsky reports no relevant conflicts of interest. Her studies were supported by NIH and NIH/NCCR grants.