Anxiety and depression are prevalent in patients with gastroesophageal reflux disease (GERD), according to a large-scale analysis that also found evidence for a possible underlying causal link between GERD and the common psychiatric conditions.
In a systematic review and meta-analysis, researchers found that anxiety and depressive symptoms were more than twice as likely in patients with GERD than in healthy controls. Among individuals with GERD, up to one-third and one-fourth were affected by anxiety and depressive symptoms, respectively.
Moreover, a Mendelian randomization analysis suggested that a genetic risk for GERD increased the risk of developing depression or anxiety and vice versa.
A genetic predisposition seems to underlie GERD and anxiety or depression, said Nicholas J. Talley, MD, PhD, School of Medicine and Public Health, University of Newcastle, Australia, and corresponding author of the review, published online in the American Journal of Gastroenterology.
Scientifically, the possible underlying link “suggests there are different disease subsets within reflux that probably have a different pathogenesis, and these relationships are an expression of whatever the underlying causal pathways are,” Dr. Talley told this news organization.
Clinically, “if you’ve got a patient with reflux, you should be asking one or two questions about anxiety and particularly depression ... because it may impact on how well patients respond to therapy, and how well they do in the longer term,” Dr. Talley said.
A deeper look
In the review, the authors note that GERD affects about 15% of the general population worldwide and has a negative impact on the health-related quality of life.
The pathogenesis is complex and may be associated with psychological distress alongside the well-known predisposing anatomical factors, aggravated by lifestyle factors such as obesity and smoking.
Individual studies examining the association between GERD and the prevalence of anxiety or depressive symptoms have had mixed results, “perhaps limited by heterogeneous study design, the severity of disease included, and diagnostic criteria for depression and anxiety,” the researchers wrote.
They therefore set out to perform a systematic review and meta-analysis to assess the issue in greater depth. They looked at three primary outcomes – the prevalence of symptoms of anxiety and depression in individuals with GERD, the epidemiological risk of developing GERD in people with anxiety or depression and vice versa, and the cause-and-effect relationship between anxiety or depression and GERD.
They searched the Embase, PubMed, Scopus, and Web of Science databases, and found 36 eligible studies published between 2003 and 2023.
Of the total, 30 were observational studies that examined the prevalence of anxiety and/or depressive symptoms using validated questionnaires in ≥ 100 individuals aged 18 years or older.
These included 26 studies of anxiety symptoms among 10,378 individuals with GERD, 30 that looked at depressive symptoms among 14,030 subjects with GERD, and four that reported the prevalence of simultaneous anxiety and depressive symptoms in 3,878 patients with GERD. Some studies were population based and others were hospital based. The extracted data were combined using a random-effects model.
The overall pooled analyses revealed a prevalence of anxiety symptoms of 34.4% among individuals with GERD, at an adjusted odds ratio versus healthy controls of 4.46 (95% confidence interval [CI], 1.94-10.25).
The pooled prevalence of depressive symptoms among those with GERD was 24.2%, at an adjusted odds ratio compared with healthy controls of 2.56 (95% CI, 1.11-5.87).
The pooled prevalence of simultaneous anxiety and depression in people with GERD was 22.3% (95% CI, 7.0-37.7).
Next, the team added three cohort studies that explored the risk for GERD in individuals with anxiety or depression in the vice versa scenario, as well as three Mendelian randomization studies that assessed the cause-and-effect relationship between anxiety or depression and GERD.
The cohort studies could not be pooled, but individuals with depression had a significantly increased risk for GERD versus those without depression, at an adjusted odds ratio in one study of 2.01 (95% CI, 1.96-2.07) and an adjusted hazard ratio in another study of 1.72 (95% CI, 1.60-1.85). A similar pattern was seen for anxiety.
The Mendelian randomization studies suggested that a genetic risk for depression was associated with an increased risk of developing GERD, at an odds ratio of 1.36 (95% CI, 1.21-1.51), and that a genetic risk for GERD was linked to an increased risk of developing depression, at an odds ratio of 1.30 (95% CI, 1.17-1.43).
One study reported a similar effect of a genetic risk for GERD on the risk for anxiety.
“We don’t really know what causes reflux disease. We know the pathophysiology, but we don’t really know what the etiology is, and depression is the same,” Dr. Talley noted. “It’s obviously thought to be a brain disease, but sometimes it might be coming from the gut as well, for all we know, and there is certainly evidence for that.”