Abstract
AbstractEmerging preclinical evidence suggests that vagal signals contribute to the development of schizophrenia-related abnormalities in brain and behavior. Whether vagal communication in general, and its impairment in particular, is a risk factor for schizophrenia in humans remains, however, unclear.Vagotomy, the surgical lesion of the vagus nerve, was routinely performed as a treatment for peptic ulcer before modern treatment options were available. Hence, the primary aim of this study was to investigate whether vagotomy modulates the subsequent risk of developing schizophrenia. Moreover, given the existence of diverse vagotomy techniques (i.e., “truncal” or “selective”), our secondary goal was to test whether the extent of denervation modulates the risk of schizophrenia.Using a nationwide retrospective matched cohort design, we identified 8,833 vagotomized individuals from the Swedish National Patient Register during the period 1970-2020 and 17,666 non-vagotomized individuals matching for age, sex and type of peptic ulcer. The risk of being diagnosed with schizophrenia and associated psychoses (ICD10 codes F20-29) was analyzed using Cox proportional hazards regression models, including death as competing risk.Overall, vagotomy was not significantly associated with schizophrenia (HR: 0.86 [0.66; 1.12]). When considering different vagotomy techniques, however, truncal vagotomy significantly increased (HR: 1.60 [1.02; 2.51]), while selective vagotomy decreased (HR: 0.75 [0.56; 1.00]), the risk of developing schizophrenia.Our results provide epidemiological support for the hypothesis that impairments in vagal functions can increase the risk of schizophrenia. Notably, the finding that truncal but not selective vagotomy is associated with an increased risk of schizophrenia raises the possibility that the activity of subdiaphragmatic non-gastric vagal branches may be of particular relevance for the development of schizophrenia.
Publisher
Cold Spring Harbor Laboratory