Gastrointestinal distress to serotonergic challenge: a risk marker for emotional disorder?

Objective: Serotonin is an important mediator of gut sensation and motility. The authors' aim was to determine whether inadvertent gastrointestinal (GI) distress to serotonergic challenge predicted future major depressive and/or anxiety disorders in exposed children.

Method: l-5-hydroxytryptophan was administered to 119 prepubertal children free of psychiatric disorder as part of a psychobiological cohort study initially designed to examine familial loading for mood disorder as the exposure of interest. Subjects were followed longitudinally with standardized psychiatric interviews to identify new-onset mood and anxiety disorders over 90.3 +/- 29.2 months, with the average assessment interval being 16.6 +/- 6.2 months. Reports of GI distress in a subgroup during serotonergic challenge led the authors to examine GI distress to infusion as an exposure post hoc and to perform survival analysis using major depressive and/or anxiety disorders as the outcomes of interest.

Results: GI distress to serotonergic challenge was experienced by 23 subjects, with 7 (30.4%) developing an emotional disorder during follow-up in comparison to 12 (10.4%) of 96 nondistressed subjects. The distressed group was at significantly greater risk of subsequent major depression and/or anxiety (p =.026), even after controlling for family history of psychiatric disorder.

Conclusions: GI distress to serotonergic challenge in childhood is associated with heightened risk for subsequent major depressive and/or anxiety disorders. Studies of serotonergic neurotransmission may aid our understanding of nonrandom associations between functional GI symptoms and emotional symptoms and disorders.