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Inflammation subtypes in psychosis and their relationships with genetic risk for psychiatric and cardiometabolic disorders.
Zhang, Lusi; Lizano, Paulo; Guo, Bin; Xu, Yanxun; Rubin, Leah H; Hill, S Kristian; Alliey-Rodriguez, Ney; Lee, Adam M; Wu, Baolin; Keedy, Sarah K; Tamminga, Carol A; Pearlson, Godfrey D; Clementz, Brett A; Keshavan, Matcheri S; Gershon, Elliot S; Sweeney, John A; Bishop, Jeffrey R.
Afiliação
  • Zhang L; Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA.
  • Lizano P; Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, USA.
  • Guo B; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
  • Xu Y; Division of Biostatistics, School of Public Health, University of Minnesota, MN, USA.
  • Rubin LH; Department of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, MD, USA.
  • Hill SK; Department of Neurology, Psychiatry, and Epidemiology, Johns Hopkins University, Baltimore, MD, USA.
  • Alliey-Rodriguez N; Department of Psychology, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.
  • Lee AM; Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
  • Wu B; Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA.
  • Keedy SK; Division of Biostatistics, School of Public Health, University of Minnesota, MN, USA.
  • Tamminga CA; Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
  • Pearlson GD; Department of Psychiatry, Southwestern Medical Center, University of Texas, Dallas, TX, USA.
  • Clementz BA; Department of Psychiatry, School of Medicine, Yale University, New Haven, CT, USA.
  • Keshavan MS; Department of Neurobiology, School of Medicine, Yale University, New Haven, CT, USA.
  • Gershon ES; Department of Psychology and Neuroscience, University of Georgia, Athens, GA, USA.
  • Sweeney JA; Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, USA.
  • Bishop JR; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
Brain Behav Immun Health ; 22: 100459, 2022 Jul.
Article em En | MEDLINE | ID: mdl-35496776
Cardiometabolic disorders have known inflammatory implications, and peripheral measures of inflammation and cardiometabolic disorders are common in persons with psychotic disorders. Inflammatory signatures are also related to neurobiological and behavioral changes in psychosis. Relationships between systemic inflammation and cardiometabolic genetic risk in persons with psychosis have not been examined. Thirteen peripheral inflammatory markers and genome-wide genotyping were assessed in 122 participants (n â€‹= â€‹86 psychosis, n â€‹= â€‹36 healthy controls) of European ancestry. Cluster analyses of inflammatory markers classified higher and lower inflammation subgroups. Single-trait genetic risk scores (GRS) were constructed for each participant using previously reported GWAS summary statistics for the following traits: schizophrenia, bipolar disorder, major depressive disorder, coronary artery disease, type-2 diabetes, low-density lipoprotein, high-density lipoprotein, triglycerides, and waist-to-hip ratio. Genetic correlations across traits were quantified. Principal component (PC) analysis of the cardiometabolic GRSs generated six PC loadings used in regression models to examine associations with inflammation markers. Functional module discovery explored biological mechanisms of the inflammation association of cardiometabolic GRS genes. A subgroup of 38% persons with psychotic disorders was characterized with higher inflammation status. These higher inflammation individuals had lower BACS scores (p â€‹= â€‹0.038) compared to those with lower inflammation. The first PC of the cardiometabolic GRS matrix was related to higher inflammation status in persons with psychotic disorders (OR â€‹= â€‹2.037, p â€‹= â€‹0.001). Two of eight modules within the functional interaction network of cardiometabolic GRS genes were enriched for immune processes. Cardiometabolic genetic risk may predispose some individuals with psychosis to elevated inflammation which adversely impacts cognition associated with illness.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
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XML
PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2022 Tipo de documento: Article