Inflammation subtypes in psychosis and their relationships with genetic risk for psychiatric and cardiometabolic disorders

Lusi Zhang; Paulo Lizano; Bin Guo; Yanxun Xu; Leah H. Rubin; S. Kristian Hill; Ney Alliey-Rodriguez; Adam M. Lee; Baolin Wu; Sarah K. Keedy; Carol A. Tamminga; Godfrey D. Pearlson; Brett A. Clementz; Matcheri S. Keshavan; Elliot S. Gershon; John A. Sweeney; Jeffrey R. Bishop

Brain, Behavior, & Immunity - Health (Jul 2022)

Inflammation subtypes in psychosis and their relationships with genetic risk for psychiatric and cardiometabolic disorders

Lusi Zhang,
Paulo Lizano,
Bin Guo,
Yanxun Xu,
Leah H. Rubin,
S. Kristian Hill,
Ney Alliey-Rodriguez,
Adam M. Lee,
Baolin Wu,
Sarah K. Keedy,
Carol A. Tamminga,
Godfrey D. Pearlson,
Brett A. Clementz,
Matcheri S. Keshavan,
Elliot S. Gershon,
John A. Sweeney,
Jeffrey R. Bishop

Affiliations

Lusi Zhang: Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA
Paulo Lizano: Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA
Bin Guo: Division of Biostatistics, School of Public Health, University of Minnesota, MN, USA
Yanxun Xu: Department of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, MD, USA
Leah H. Rubin: Department of Neurology, Psychiatry, and Epidemiology, Johns Hopkins University, Baltimore, MD, USA
S. Kristian Hill: Department of Psychology, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA
Ney Alliey-Rodriguez: Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA
Adam M. Lee: Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA
Baolin Wu: Division of Biostatistics, School of Public Health, University of Minnesota, MN, USA
Sarah K. Keedy: Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA
Carol A. Tamminga: Department of Psychiatry, Southwestern Medical Center, University of Texas, Dallas, TX, USA
Godfrey D. Pearlson: Department of Psychiatry, School of Medicine, Yale University, New Haven, CT, USA; Department of Neurobiology, School of Medicine, Yale University, New Haven, CT, USA
Brett A. Clementz: Department of Psychology and Neuroscience, University of Georgia, Athens, GA, USA
Matcheri S. Keshavan: Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA
Elliot S. Gershon: Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA
John A. Sweeney: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH, USA
Jeffrey R. Bishop: Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA; Department of Psychiatry and Behavioral Sciences, University of Minnesota Medical School, Minneapolis, MN, USA; Corresponding author. University of Minnesota College of Pharmacy, 308 Harvard St SE, Minneapolis, MN, 55455, USA.

Journal volume & issue: Vol. 22
p. 100459

Abstract

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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 = 86 psychosis, n = 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 = 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 = 2.037, p = 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.

Published in Brain, Behavior, & Immunity - Health

ISSN: 2666-3546 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/brain-behavior-and-immunity-health

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