Possible causal link between eosinophilic inflammation and anxiety

After a 10-year follow-up, anxiety at baseline was independently associated with a 15-fold increased risk of eosinophilia, while anxiety at follow-up was associated with a 5-fold increased risk with duodenal eosinophilia [1]. A prospective population-based study from Sweden demonstrated for the first time a possible causal link between duodenal inflammation and psychological distress in a functional gut disorder.

Functional dyspepsia is a distressing, frequent disorder with a prevalence of approximately 15% in the general population. Anxiety was found to be strongly associated with new-onset functional dyspepsia. In addition, increased duodenal eosinophil counts have been observed in patients with functional dyspepsia. Gut symptoms may precede the development of anxiety in patients with a functional gut disorder. However, the underlying mechanisms are unknown. Duodenal eosinophilia is a potential cause of anxiety.

Population-based study from Sweden

From the national Swedish population register, 3,000 people were randomly selected. Subsequently, the participants were surveyed by the validated Abdominal Symptom Questionnaire (ASQ) and the Hospital Anxiety and Depression Scale (HADS). An oesophagogastroduodenoscopy was performed in 1,000 participants. All persons who were eligible from the latter cohort (n=887, response rate 79%), were invited to a follow-up with the ASQ and HADS. Functional dyspepsia was defined based on the Rome III. Anxiety and depression were defined by a score of ≥11 on the HADS.

In a nested case-control study, 89 patients with functional dyspepsia were compared with 124 healthy controls (mean age 62 years, 34% male). Duodenal histology was evaluated at baseline and divided into 2 groups, based on a pre-specified cut-off for the eosinophil count in the duodenal bulb:

• D1: cut-off of 23 eosinophils; and
• D2: cut-off of 24 eosinophils in the second part.

Duodenal eosinophilia and anxiety

Duodenal eosinophilia was observed in 78 subjects in D1 and 84 subjects in D2 (in 46 subjects, both in D1 and in D2, P<0.001 for both) at baseline. Anxiety at baseline was found in 9 subjects (4%) and at follow-up in 12 subjects (6%).

After adjustment for age, gender, and functional dyspepsia status at baseline, the following associations between anxiety and duodenal eosinophilia were observed:

• Anxiety at baseline was independently associated with duodenal eosinophilia in D2 (P=0.013, OR=15.0), but not in D1 (P=0.2).
• Anxiety at follow-up was independently associated with duodenal eosinophilia in D1 at baseline (P=0.025, OR=5.90), but not D2 (P=0.5).
• Anxiety at follow-up was independently associated with functional dyspepsia at baseline (P=0.004, OR=7.42).

New-onset anxiety was more common in individuals meeting criteria for eosinophilia in D1 (7.5%) than those who did not meet the criteria (1.8%). The association was strong (OR=4.48), but failed to reach statistical significance (P=0.08). Hence, duodenal eosinophilia may be one mechanism by which anxiety arises in functional dyspepsia.

1. Ronkainen J. Inter-relationships of duodenal eosinophilia, anxiety and functional dyspepsia. UEG Week Virtual Symposium 2020, abstract OP158.

Posted on 2 November, 20202 November, 2020