Does Reverse Causality Underlie the Temporal Relationship Between Depression and Crohn's Disease?

Studies suggest that there is a temporal relationship between depression and Crohn's disease (CD) activity. However, these studies assumed a unidirectional relationship and did not examine the possibility of reverse causality and the risk of a spurious association due to the overlap of symptoms underlying the depression-CD relationship. We evaluated the existence of reverse causality reflected in a possible bidirectional relationship between patient-reported CD activity and an affective-cognitive dimension of depression.

We studied 3307 adult volunteers with a self-reported diagnosis of CD who completed a baseline survey that included demographics, CD activity, and an affective-cognitive index of depression. Crohn's disease status and the affective-cognitive index of depression were also measured 6 and 12 months after the baseline evaluation. We used structural equation models to evaluate whether the effect of depression on future CD activity is stronger than the effect of CD activity on future depression. We calculated the likelihood that each of these hypotheses is supported by the data and calculated the likelihood ratio to provide a relative measure of which hypothesis best accounts for the data.

The results of the informative hypothesis testing showed the most support for the hypothesis stating that an affective-cognitive dimension of depression is a stronger predictor of patient-reported CD activity than the converse.

The hypothesis that an affective-cognitive dimension of depression predicts patient-reported exacerbation of CD is 218 times more likely to account for the data than the converse.