Photo Credit: Ekaterina Chizhevskaya

People with Crohn’s disease (CD) and fatigue may also have reduced gray matter volume (GMV), according to findings published in the Journal of Crohn’s and Colitis.

“Our study detected associations between fatigue symptoms and regional GMV in the left precentral gyrus, right fusiform gyrus, and right lingual gyrus, but no associations between GMV and depression or anxiety scores,” R. Christian Wolf, MD, and colleagues wrote. “This relationship appears to be more distinct in persistent fatigue during remitted disease, suggesting a stronger role of disturbed brain-gut interactions for fatigue in the absence of inflammation.”

Patients with CD chronically alternate between remission, with freedom from abdominal or extraintestinal symptoms, and relapses, with acute active flares. Fatigue and affective symptoms are known to be more frequent during active CD, and even in remission, almost 50% of patients with inflammatory bowel disease (IBD) experience fatigue, nearly 40% from anxiety, and up to 25% from depressive symptoms.

Study Parameters

In a prospective observational study, Dr. Wolf and colleagues investigated links between brain structure, fecal calprotectin, and symptoms of fatigue, depression, and anxiety in people with active and remitted CD. Participants included 37 healthy controls, 30 patients with active CD, and 23 with remitted CD. Controls and patients were similar in age and sex.

All participants with CD were in stable remission with a Crohn’s Disease Activity Index (CDAI) of less than 150, a C-reactive protein level of less than 5 mg/dl, and a fecal calprotectin level of less than 150 mg/kg, no change in therapy during the previous 6 months, were naïve to biologics, and were not currently taking corticosteroids. Patients in the active CD group were in an active phase of disease determined by endoscopy, MRI, sonography, and/or repeatedly elevated levels of fecal calprotectin of more than 250 mg/kg and were scheduled for a change in therapy.

All participants had their anxiety and depression assessed by the Hospital Anxiety and Depression Scale [HADS] screening tool, and their fatigue assessed by the Würzburg Fatigue Inventory in Multiple Sclerosis [WEIMuS] scale. Higher HADS scores indicate greater anxiety, depression, or both, and higher WEIMuS scores indicate greater fatigue.

Participants completed the questionnaires, provided stool samples to test fecal calprotectin, and underwent cranial MRI equipped with a 20-channel multi-array head coil. The researchers analyzed differences in GMV between controls and patients as well as links between regional GMV changes, neuropsychiatric symptoms, and fecal calprotectin.

Patients With CD Versus Controls

• Differences between healthy controls and patients were significant in HADS anxiety and depression scores (P=0.004 and P<0.001, respectively).
• HADS anxiety and HADS depression screenings showed significant differences between healthy controls and the active CD group (P=0.002 and P<0.001, respectively) but not between healthy controls and the remitted CD group or between the remitted and active CD groups.
• WEIMuS total scores showed differences in fatigue between healthy controls and patients, healthy controls and remitted CD, and healthy controls and active CD (P<0.001, P=0.002, and P<0.001, respectively), but not between remitted CD and active CD.
• In patients, there were significant correlations between WEIMuS total score and GMV of the left precentral gyrus, right fusiform gyrus, and right lingual gyrus (rho=-0.32, -0.39, and -0.35, respectively). Subgroup analyses showed significant correlations between WEIMuS total score and GMV of the left precentral gyrus and right gyrus rectus (rho=-0.49 and -0.4, respectively) in remitted CD but not in active CD.
• On MRI, healthy controls showed greater GMV than patients in the left precentral gyrus and its medial segment, left cerebellum, right lingual gyrus, right cuneus, right fusiform gyrus, and gyrus rectus (P<0.001).
• Fecal calprotectin concentrations were significantly lower in remitted CD than in active CD (P<0.001)
• Most links between GMV and fecal calprotectin were negative and were located in the frontal, temporal, parietal, occipital, cerebellar, and subcortical areas (P<0.005).
• Fecal calprotectin in remitted CD correlated significantly with the left precentral gyrus and the right cuneus (rho=0.41 and 0.40, respectively).

“Future studies of fatigue in IBD should address differences between active and remitted IBD, as different disease states may warrant different therapeutic approaches to target the symptom,” the authors recommend. “If a contribution of structural abnormalities in the precentral gyrus, which may also affect regional brain function, is confirmed in the pathogenesis of CD-related fatigue, noninvasive brain stimulation such as transcranial magnetic stimulation may represent a promising and novel therapeutic approach to target fatigue in IBD.”