From gut to brain: A network model of intestinal permeability, inflammation, and psychotic symptoms in schizophrenia.

Francesco Dal Santo, Leticia González-Blanco, María Paz García-Portilla, Miqueu Alfonso, Carla Hernandez, Monica Sanchez-Autet, Miquel Bernardo, Gerard Anmella, Silvia Amoretti, Gemma Safont, Lorena Marín Alcaraz, Belén Arranz

Journal: European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 2024;79():32-37

PMID: 38086222

Free Full Text on Elsevier Science View on PubMed

Abstract

Impaired intestinal permeability has recently been suggested as a possible source of chronic inflammation in schizophrenia, but its association with specific psychopathological features remains uncertain. This study aimed to explore the interaction between intestinal permeability, inflammation, and positive and negative symptoms in schizophrenia using a network analysis approach. The study sample comprised 281 adults with schizophrenia (age 40.29 ± 13.65 years, 63.0 % males), enrolled in a cross-sectional observational study assessing intestinal permeability. We estimated the network with a Gaussian graphical model, incorporating scores from 14 individual items of the Positive and Negative Syndrome Scale (PANSS), along with body mass index (BMI), and plasma C-reactive protein (CRP) and lipopolysaccharide-binding protein (LBP) levels. We calculated strength centrality and expected influence and used bridge centrality statistics to identify the bridge nodes. Distinct but highly interconnected clusters emerged for positive and negative symptoms. The biological variables were closely associated with each other. LBP was positively linked with CRP and BMI, but only indirectly connected to psychopathology. CRP exhibited direct positive relationships with various PANSS items and bridged LBP and BMI with psychopathology. Bridge nodes included Conceptual Disorganisation (P2), Active Social Avoidance (G16), Suspiciousness/Persecution (P6), and CRP. These findings support the role of gut-derived inflammation as a mechanism underlying greater symptom severity in schizophrenia and emphasise the importance of addressing dietary habits not only to enhance physical health but also to contribute to improving psychotic symptoms.

Address: Área de Psiquiatría, Universidad de Oviedo, Oviedo, Spain; Servicio de Salud del Principado de Asturias (SESPA), Oviedo, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain; Instituto de Neurociencias del Principado de Asturias (INEUROPA), Oviedo, Spain.; Área de Psiquiatría, Universidad de Oviedo, Oviedo, Spain; Servicio de Salud del Principado de Asturias (SESPA), Oviedo, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain; Instituto de Neurociencias del Principado de Asturias (INEUROPA), Oviedo, Spain; Biomedical Research Networking Centre for Mental Health Network (CIBERSAM), Oviedo, Spain.; Área de Psiquiatría, Universidad de Oviedo, Oviedo, Spain; Servicio de Salud del Principado de Asturias (SESPA), Oviedo, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain; Instituto de Neurociencias del Principado de Asturias (INEUROPA), Oviedo, Spain; Biomedical Research Networking Centre for Mental Health Network (CIBERSAM), Oviedo, Spain. Electronic address: [email protected].; Department of Psychiatry, Hospital Parc Sanitari Sant Joan de Déu, Barcelona, Spain; Biomedical Research Networking Centre for Mental Health Network (CIBERSAM), Barcelona, Spain.; Biomedical Research Networking Centre for Mental Health Network (CIBERSAM), Barcelona, Spain; Barcelona Clinic Schizophrenia Unit, Hospital Clinic, Barcelona, Spain; Departament de Medicina, Institut de Neurociències (UBNeuro), Universitat de Barcelona (UB), Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain.; Department of Psychiatry and Psychology, Institute of Neuroscience, Hospital Clínic, Barcelona, Spain; Bipolar and Depressive Disorders Unit, Digital Innovation Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Biomedical Research Networking Centre Consortium on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain; Department of Medicine, School of Medicine and Health Sciences, University of Barcelona (UB), Barcelona, Spain; Institute of Neurosciences (UBNeuro), University of Barcelona, Barcelona, Spain.; Biomedical Research Networking Centre for Mental Health Network (CIBERSAM), Barcelona, Spain; Barcelona Clinic Schizophrenia Unit, Hospital Clinic, Barcelona, Spain; Departament de Medicina, Institut de Neurociències (UBNeuro), Universitat de Barcelona (UB), Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain; Department of Psychiatry, Hospital Universitari Vall d'Hebron, Group of Psychiatry, Mental Health and Addictions, Psychiatric Genetics Unit, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain; Universitat Autònoma de Barcelona, Barcelona, Spain.; Biomedical Research Networking Centre for Mental Health Network (CIBERSAM), Barcelona, Spain; Department of Psychiatry, University Hospital Mutua Terrassa, University of Barcelona, Barcelona, Spain.; Department of Psychiatry, University Hospital Mutua Terrassa, University of Barcelona, Barcelona, Spain.

DOI: 10.1016/j.euroneuro.2023.10.004