Gut and oral microbiome modulate molecular and clinical markers of schizophrenia-related symptoms: A transdiagnostic, multilevel pilot study.

Although increasing evidence links microbial dysbiosis with the risk for psychiatric symptoms through the microbiome-gut-brain axis (MGBA), the specific mechanisms remain poorly characterized. In a diagnostically heterogeneous group of treated psychiatric cases and nonpsychiatric controls, we characterized the gut and oral microbiome, plasma cytokines, and hippocampal inflammatory processes via proton magnetic resonance spectroscopic imaging (1H-MRSI). Using a transdiagnostic approach, these data were examined in association with schizophrenia-related symptoms measured by the Positive and Negative Syndrome Scale (PANSS). Psychiatric cases had significantly greater heterogeneity of gut alpha diversity and an enrichment of pathogenic taxa, like Veillonella and Prevotella, in the oral microbiome, which was an accurate classifier of phenotype. Cases exhibited significantly greater positive, negative, and general PANSS scores that uniquely correlated with bacterial taxa. Strong, positive correlations of bacterial taxa were also found with cytokines and hippocampal gliosis, dysmyelination, and excitatory neurotransmission. This pilot study supports the hypothesis that the MGBA influences psychiatric symptomatology in a transdiagnostic manner. The relative importance of the oral microbiome in peripheral and hippocampal inflammatory pathways was highlighted, suggesting opportunities for probiotics and oral health to diagnose and treat psychiatric conditions.

An integrative study of the microbiome gut-brain-axis and hippocampal inflammation in psychosis: Persistent effects from mode of birth.

The mechanism producing psychosis appears to include hippocampal inflammation, which could be associated with the microbiome-gut-brain-axis (MGBS). To test this hypothesis we are conducting a multidisciplinary study, herein described. The procedures are illustrated with testing of a single subject and group level information on the impact of C-section birth are presented. METHOD: Study subjects undergo research diagnostic interviews and symptom assessments to be categorized into one of 3 study groups: psychosis, nonpsychotic affective disorder or healthy control. Hippocampal volume and metabolite concentrations are assessed using 3-dimensional, multi-voxel H1 Magnetic Resonance Imaging (MRSI) encompassing all gray matter in the entire hippocampal volume. Rich self-report information is obtained with the PROMIS interview, which was developed by the NIH Commons for research in chronic conditions. Early trauma is assessed and cognition is quantitated using the MATRICS. The method also includes the most comprehensive autonomic nervous system (ANS) battery used to date in psychiatric research. Stool and oral samples are obtained for microbiome assessments and cytokines and other substances are measured in blood samples. RESULTS: Group level preliminary data shows that C-section birth is associated with higher concentrations of GLX, a glutamate related hippocampal neurotransmitter in psychotic cases, worse symptoms in affective disorder cases and smaller hippocampal volume in controls. CONCLUSION: Mode of birth appears to have persistent influences through adulthood. The methodology described for this study will define pathways through which the MGBA may influence the risk for psychiatric disorders.

Ineffective risk-reward learning in schizophrenia.

The underpinnings of poor decision-making in schizophrenia could reflect excessively risky or inhibited behaviors. This study employed the Balloon Analogue Risk Task (BART) to compare decision-making in schizophrenia cases to that of healthy controls. Individuals with schizophrenia performed significantly differently across three trials, failing to improve their performance as shown by the control group. In the control group, cognitive ability, measured with the Wechsler Adult Intelligence Scale (WAIS-III) showed that Perceptual Organization scores predicted Average Inflations per Trial, Total Balloon Pops, and Total Earnings. Although the schizophrenia cases failed to learn, group performance on the BART was not associated with cognitive ability, but regression analyses showed 41.4% of average inflations per trial were explained by Excitement, Delusions, Emotional Withdrawal, and Poor Rapport; total balloon pops were only explained by emotional withdrawal and Total Earnings were reduced by Delusions, Excitement and Poor Rapport. Only healthy participants demonstrated a relation between cognitive ability performance improvement across trials. Schizophrenia cases showed less risk-taking, and earned significantly less money overall. Identifying the determinants of poor decision-making could inform interventions and possible treatments to improve their function and perhaps be of relevance to public safety if decisions are overly risky.