Patient-reported exposures and outcomes link the gut-brain axis and inflammatory pathways to specific symptoms of severe mental illness

We developed a “gut-brain-axis questionnaire” (GBAQ) to obtain standardized person-specific “review of systems” data for microbiome-gut-brain-axis studies. Individual items were compared to PANSS symptom measures using dimensional, transdiagnostic and traditional categorical approaches. Method: Forty psychotic participants, independent of diagnoses, and 42 without psychosis (18 nonpsychotic affective disorders, 24 healthy controls) completed the GBAQ and underwent research diagnostic and symptom assessments. The PANSS scales and its dysphoric mood, autistic preoccupation and activation factors were computed. Results: Transdiagnostic analyses robustly linked psychosis severity to constipation (p<.001), and Negative (p=.045) and General Psychopathology scores (p=.016) with bowel hypomotility. Activation factor scores predicted numbers of psychiatric (p=.009) and medical conditions (p=.003), BMI (p=.003), skin (p<.001) and other conditions. Categorical analyses comparing psychotic, nonpsychotic and control groups revealed behavioral differences: cigarette smoking (p=.013), alcohol use (p=.007), diet (p's <.05), exercise (p<.001). All subjects accurately self-reported their diagnosis. Conclusions: The GBAQ is a promising tool. Transdiagnostic analyses associated psychotic symptoms to gut hypomotility, indicative of low gut vagal tone, consistent with reduced cardiovagal activity in psychosis. Activation, similar to delirium symptoms, predicted medical comorbidity and systemic inflammatory conditions. Group level comparisons only showed behavioral differences. Underpinnings of psychiatric disorders may include reduced gut vagal function, producing psychosis, and systemic inflammation, impacting risks for psychotic and nonpsychotic conditions.