Serum LBP and zonulin levels with brain MRS findings and gastrointestinal symptoms in schizophrenia and health

Introduction: Schizophrenia is a chronic, severe psychiatric disorder characterised by abnormal peripheral immune response parameters, central neuroinflammatory processes and blood-brain barrier disregulation. Schizophrenia is thoroughly studied in the gut-brain axis paradigm, showing comorbidity with gastrointestinal disorders. Studies show variations in serum biomarkers of intestinal barrier permeability, zonulin and lipopolysaccharide binding protein (LBP) in schizophrenia. The function of LBP as an acute-phase class I protein and zonulin as a pre-haptoglobin-2 may play a significant role in neuroinflammation. Meta-analyses of brain magnetic resonance spectroscopy (MRS) show irregular metabolite concentrations in patients with schizophrenia. Material and methods: 28 patients with schizophrenia (SCZ) in remission and 29 healthy participants (CON) were involved in the study. All participants underwent a brain MRS 3T examination in the anterior (ACC) and posterior cingulate cortex (PCC), laboratory blood tests, and fulfilled the Gastrointestinal Symptoms Rating Scale (GSRS). SCZ were evaluated with Positive and Negative Syndrome Scale (PANSS). Results: The groups differed in serum LBP levels (SCZ: 11ug/ml vs CON: 7.9ug/ml; p = 0.02) and did not differ in serum zonulin levels. The partial correlation analysis, controlled for age, ALT, HOMA-IR, and daily neuroleptic dose, revealed a serum LBP association with myo-inositol in PCC (r = -0.49; p < 0.05) in SCZ and in CON (r = -0.46; p < 0.05). In SCZ, serum zonulin correlated with glutamine in ACC (r = -0.43; p < 0.05). LBP correlated with age of onset (r = -0.46; p < 0.05) and lower gastrointestinal symptoms (r = 0.54; p < 0.01) in SCZ, and with upper gastrointestinal symptoms in CON (r = 0.53; p < 0.05). No significant associations between PANSS subscales with LBP or zonulin levels were observed. Conclusions: This is the first study to assess intestinal permeability markers with brain MRS findings in health and in schizophrenia. Results indicate associations between LBP and myo-inositol in PCC in health and in schizophrenia, suggesting a physiological role of LBP in glial homeostasis. Zonulin association with glutamine levels in ACC may contribute to the complex pathophysiology of schizophrenia. Patients with schizophrenia exhibited increased levels of LBP, which is associated with age of onset and discomfort from lower gastrointestinal symptoms. Healthy controls show associations between LBP and upper gastrointestinal symptoms. A closer examination of the gut-brain axis may provide novel insights into the neuroimmune dysregulation in schizophrenia.