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      Immuno-metabolic profile of patients with psychotic disorders and metabolic syndrome. Results from the FACE-SZ cohort

      research-article
      a , b , c , d , a , b , c , b , c , b , c , c , e , 1 , c , f , g , 1 , c , h , 1 , i , c , e , 1 , c , h , 1 , c , j , 1 , d , c , k , 1 , c , l , m , 1 , c , n , 1 , c , o , 1 , c , o , 1 , c , n , 1 , c , i , 1 , c , l , m , 1 , c , p , q , 1 , d , c , r , 1 , c , k , 1 , a , b , c , 1 , c , r , 1 , a , b , c , 1 , d , a , b , c , ∗∗ , 2 , a , b , c , , 2 , the FACE-SZ (FondaMental Academic Centers of Expertise for Schizophrenia) Groups 1
      Brain, Behavior, & Immunity - Health
      Elsevier
      Metabolic syndrome, Schizophrenia, Psychosis, Inflammation, Machine learning, Precision medicine

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          Abstract

          Background

          Metabolic syndrome (MetS) is a highly prevalent and harmful medical disorder often comorbid with psychosis where it can contribute to cardiovascular complications. As immune dysfunction is a key shared component of both MetS and schizophrenia (SZ), this study investigated the relationship between immune alterations and MetS in patients with SZ, whilst controlling the impact of confounding clinical characteristics including psychiatric symptoms and comorbidities, history of childhood maltreatment and psychotropic treatments.

          Method

          A total of 310 patients meeting DSM-IV criteria for SZ or schizoaffective disorders (SZA), with or without MetS, were systematically assessed and included in the FondaMental Advanced Centers of Expertise for Schizophrenia (FACE-SZ) cohort. Detailed clinical characteristics of patients, including psychotic symptomatology, psychiatric comorbidities and history of childhood maltreatment were recorded and the serum levels of 18 cytokines were measured. A penalized regression method was performed to analyze associations between inflammation and MetS, whilst controlling for confounding factors.

          Results

          Of the total sample, 25% of patients had MetS. Eight cytokines were above the lower limit of detection (LLOD) in more than 90% of the samples and retained in downstream analysis. Using a conservative Variable Inclusion Probability (VIP) of 75%, we found that elevated levels of interleukin (IL)-6, IL-7, IL-12/23 p40 and IL-16 and lower levels of tumor necrosis factor (TNF)-α were associated with MetS. As for clinical variables, age, sex, body mass index (BMI), diagnosis of SZ (not SZA), age at the first episode of psychosis (FEP), alcohol abuse, current tobacco smoking, and treatment with antidepressants and anxiolytics were all associated with MetS.

          Conclusion

          We have identified five cytokines associated with MetS in SZ suggesting that patients with psychotic disorders and MetS are characterized by a specific “immuno-metabolic” profile. This may help to design tailored treatments for this subgroup of patients with both psychotic disorders and MetS, taking one more step towards precision medicine in psychiatry.

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          Most cited references83

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          Regularization Paths for Generalized Linear Models via Coordinate Descent

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            The Positive and Negative Syndrome Scale (PANSS) for Schizophrenia

            The variable results of positive-negative research with schizophrenics underscore the importance of well-characterized, standardized measurement techniques. We report on the development and initial standardization of the Positive and Negative Syndrome Scale (PANSS) for typological and dimensional assessment. Based on two established psychiatric rating systems, the 30-item PANSS was conceived as an operationalized, drug-sensitive instrument that provides balanced representation of positive and negative symptoms and gauges their relationship to one another and to global psychopathology. It thus constitutes four scales measuring positive and negative syndromes, their differential, and general severity of illness. Study of 101 schizophrenics found the four scales to be normally distributed and supported their reliability and stability. Positive and negative scores were inversely correlated once their common association with general psychopathology was extracted, suggesting that they represent mutually exclusive constructs. Review of five studies involving the PANSS provided evidence of its criterion-related validity with antecedent, genealogical, and concurrent measures, its predictive validity, its drug sensitivity, and its utility for both typological and dimensional assessment.
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              Inflammaging: a new immune–metabolic viewpoint for age-related diseases

              Ageing and age-related diseases share some basic mechanistic pillars that largely converge on inflammation. During ageing, chronic, sterile, low-grade inflammation - called inflammaging - develops, which contributes to the pathogenesis of age-related diseases. From an evolutionary perspective, a variety of stimuli sustain inflammaging, including pathogens (non-self), endogenous cell debris and misplaced molecules (self) and nutrients and gut microbiota (quasi-self). A limited number of receptors, whose degeneracy allows them to recognize many signals and to activate the innate immune responses, sense these stimuli. In this situation, metaflammation (the metabolic inflammation accompanying metabolic diseases) is thought to be the form of chronic inflammation that is driven by nutrient excess or overnutrition; metaflammation is characterized by the same mechanisms underpinning inflammaging. The gut microbiota has a central role in both metaflammation and inflammaging owing to its ability to release inflammatory products, contribute to circadian rhythms and crosstalk with other organs and systems. We argue that chronic diseases are not only the result of ageing and inflammaging; these diseases also accelerate the ageing process and can be considered a manifestation of accelerated ageing. Finally, we propose the use of new biomarkers (DNA methylation, glycomics, metabolomics and lipidomics) that are capable of assessing biological versus chronological age in metabolic diseases.
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                Author and article information

                Contributors
                Journal
                Brain Behav Immun Health
                Brain Behav Immun Health
                Brain, Behavior, & Immunity - Health
                Elsevier
                2666-3546
                29 March 2022
                July 2022
                29 March 2022
                : 22
                : 100436
                Affiliations
                [s ]FACE-SZ Clinical Coordinating Center (Fondation FondaMental), France
                [t ]FACE-SZ Data Coordinating Center (Fondation FondaMental), France
                [u ]FACE-SZ Clinical Sites and Principal Collaborators in France, France
                [v ]AP-HP, INSERM U955, Translational Psychiatry Team, DHU Pe-PSY, Centre Expert Schizophrénie, Pôle de Psychiatrie et d’Addictologie des Hôpitaux Universitaires Henri Mondor, Paris Est University, 40 rue de Mesly, 94000, Créteil, France
                [w ]Department of Adult Psychiatry, Charles Perrens Hospital, F-33076, Bordeaux, France
                [x ]Laboratory of Nutrition and Integrative Neurobiology (UMR INRA 1286), University of Bordeaux, France
                [y ]University of Bordeaux, CNRS UMR 5287-INCIA, Bordeaux, France
                [z ]CHU Clermont-Ferrand, Department of Psychiatry (service de psychatrie B), University of Clermont Auvergne, Clermont-Ferrand, France
                [aa ]AP-HP, Department of Psychiatry, Louis Mourier Hospital, Colombes, Inserm UMR1266, Institute of Psychiatry and Neurosciences of Paris, University Paris Descartes, Université Paris Diderot, Sorbonne Paris Cité, Faculté de médecine, France
                [ab ]Psychosocial Rehabilitation Reference Center, Alpes Isère Hospital, Grenoble, France
                [ac ]University Claude Bernard Lyon 1, Le Vinatier Hospital Pole Est BP 300 39, 95 bd Pinel, 69678, Bron Cedex, France
                [ad ]Department of Psychiatry (AP-HM), Sainte-Marguerite University Hospital, Marseille, France
                [ae ]AP-HM, la Conception Hospital, Aix-Marseille Univ, School of medicine - La Timone Medical Campus, EA 3279, France
                [af ]CEReSS - Health Service Research, France
                [ag ]Strasbourg University Hospital, University of Strasbourg, INSERM U1114, Federation of Translational Psychiatry, Strasbourg, France
                [ah ]University Department of Adult Psychiatry, La Colombiere Hospital, CHU Montpellier, University of Montpellier 1, Inserm 1061, Montpellier, France
                [ai ]Department of Adult Psychiatry, Versailles Hospital, Le Chesnay, France
                [aj ]HandiRESP and Quality of Life Center, 27 Boulevard Jean Moulin, 13005, Marseille, France
                [ak ]France Laboratory, EA4047, UFR Health Sciences Simone Veil, Université de Versailles Saint-Quentin-En-Yvelines, Montigny-le-Bretonneux, France
                [a ]Univ Paris Est Créteil, INSERM U955, IMRB, Translational NeuroPsychiatry Laboratory, F-94010, Créteil, France
                [b ]AP-HP, Hôpitaux Universitaires Henri Mondor, Département Médico-Universitaire de Psychiatrie et d’Addictologie (DMU IMPACT), Fédération Hospitalo-Universitaire de Médecine de Précision en Psychiatrie (FHU ADAPT), F-94010, France
                [c ]Fondation FondaMental, France
                [d ]Université Côte d’Azur, Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France
                [e ]Service Universitaire de Psychiatrie Adulte, Hôpital la Colombière, CHRU Montpellier, Université Montpellier 1, Inserm 1061, Montpellier, France
                [f ]Centre Hospitalier Charles Perrens, Université de Bordeaux, Bordeaux, F-33076, France
                [g ]INRAE, NutriNeuro, University of Bordeaux, U1286, Bordeaux, F-33076, France
                [h ]Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, INSERM U1114, Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France
                [i ]APHP, Hôpital Henri Mondor, Plateforme de Ressources Biologiques, France
                [j ]CHU Clermont-Ferrand, Department of Psychiatry, University of Clermont Auvergne, EA 7280, Clermont-Ferrand, France
                [k ]INSERM U1028, CNRS UMR5292, Centre de Recherche en Neurosciences de Lyon, Université Claude Bernard Lyon 1, Equipe PSYR2, Centre Hospitalier Le Vinatier, France
                [l ]AP-HP, Groupe Hospitalo-Universitaire AP-HP Nord, service de Psychiatrie et Addictologie, Hopital Louis Mourier, Colombes, France
                [m ]Université de Paris INSERM UMR1266, Institute of Psychiatry and Neuroscience of Paris, France
                [n ]Centre Référent de Réhabilitation Psychosociale et de Remédiation Cognitive (C3R), CH Alpes Isère, France
                [o ]AP-HM, Aix-Marseille Univ, School of Medicine - La Timone Medical Campus, EA 3279, CEReSS - Health Service Research and Quality of Life Center, Marseille, France
                [p ]Department of Adult Psychiatry, Charles Perrens Hospital, Bordeaux, France
                [q ]University of Bordeaux, CNRS UMR 5287-INCIA « Neuroimagerie et cognition humaine », France
                [r ]Service Universitaire de psychiatrie et d'addictologie du Centre Hospitalier de Versailles, INSERM UMR1018, CESP, Team “DevPsy”, Université de Versailles Saint-Quentin-en-Yvelines, Paris, Saclay, France
                [d ]Université Côte d’Azur, Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France
                [a ]Univ Paris Est Créteil, INSERM U955, IMRB, Translational NeuroPsychiatry Laboratory, F-94010, Créteil, France
                [b ]AP-HP, Hôpitaux Universitaires Henri Mondor, Département Médico-Universitaire de Psychiatrie et d’Addictologie (DMU IMPACT), Fédération Hospitalo-Universitaire de Médecine de Précision en Psychiatrie (FHU ADAPT), F-94010, France
                [c ]Fondation FondaMental, France
                Author notes
                []Corresponding author. Département Hospitalo-Universitaire de Psychiatrie, Hôpital Albert Chenevier, 40 rue de Mesly, Créteil, 94000, France. tamouza.ryad@ 123456gmail.com
                [∗∗ ]Corresponding author. Département Hospitalo-Universitaire de Psychiatrie, Hôpital Albert Chenevier, 40 rue de Mesly, Créteil, 94000, France. marion.leboyer@ 123456inserm.fr
                [1]

                FondaMental Academic Centers of Expertise for Schizophrenia.

                [2]

                Senior co-authors: ML,RT.

                Article
                S2666-3546(22)00026-6 100436
                10.1016/j.bbih.2022.100436
                9034311
                35469211
                d5ff5fcf-a041-4588-9989-5f499abfbd60
                © 2022 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 25 February 2022
                : 26 February 2022
                Categories
                Full Length Article

                metabolic syndrome,schizophrenia,psychosis,inflammation,machine learning,precision medicine

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