Peripheral inflammation is associated with impairments of inhibitory behavioral control and visual sensorimotor function in psychotic disorders

Lusi Zhang; Paulo Lizano; Yanxun Xu; Leah H Rubin; Adam M Lee; Rebekka Lencer; James L Reilly; Richard S E Keefe; Sarah K Keedy; Godfrey D Pearlson; Brett A Clementz; Matcheri S Keshavan; Elliot S Gershon; Carol A Tamminga; John A Sweeney; S Kristian Hill; Jeffrey R Bishop

doi:10.1016/j.schres.2023.03.030

Peripheral inflammation is associated with impairments of inhibitory behavioral control and visual sensorimotor function in psychotic disorders

Schizophr Res. 2023 May:255:69-78. doi: 10.1016/j.schres.2023.03.030. Epub 2023 Mar 23.

Authors

Lusi Zhang¹, Paulo Lizano², Yanxun Xu³, Leah H Rubin⁴, Adam M Lee¹, Rebekka Lencer⁵, James L Reilly⁶, Richard S E Keefe⁷, Sarah K Keedy⁸, Godfrey D Pearlson⁹, Brett A Clementz¹⁰, Matcheri S Keshavan¹¹, Elliot S Gershon⁸, Carol A Tamminga¹², John A Sweeney¹³, S Kristian Hill¹⁴, Jeffrey R Bishop¹⁵

Affiliations

¹ Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, United States.
² Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, United States; Department of Psychiatry, Harvard Medical School, Boston, MA, United States; Division of Translational Neuroscience, Beth Israel Deaconess Medical Center, Boston, MA, United States.
³ Department of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, MD, United States.
⁴ Department of Neurology, Psychiatry, and Epidemiology, Johns Hopkins University, Baltimore, MD, United States.
⁵ Institute for Translational Psychiatry, University of Münster, Münster, Germany; Department of Psychiatry and Psychotherapy, University of Lübeck, Lübeck, Germany.
⁶ Department of Psychiatry and Behavioral Sciences, Northwestern University, Chicago, IL, United States.
⁷ Departments of Psychiatry, Neuroscience, and Psychology, Duke University, Durham, NC, United States.
⁸ Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, United States.
⁹ Departments of Psychiatry and Neurobiology, School of Medicine, Yale University, New Haven, CT, United States.
¹⁰ Department of Psychology and Neuroscience, University of Georgia, Athens, GA, United States.
¹¹ Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, United States; Department of Psychiatry, Harvard Medical School, Boston, MA, United States.
¹² Department of Psychiatry, University of Texas Southwestern Medical Center Dallas, TX, United States.
¹³ Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH, United States.
¹⁴ Department of Psychology, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United States.
¹⁵ Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, United States; Department of Psychiatry and Behavioral Sciences, University of Minnesota Medical School, Minneapolis, MN, United States. Electronic address: jrbishop@umn.edu.

Abstract

Elevated markers of peripheral inflammation are common in psychosis spectrum disorders and have been associated with brain anatomy, pathology, and physiology as well as clinical outcomes. Preliminary evidence suggests a link between inflammatory cytokines and C-reactive protein (CRP) with generalized cognitive impairments in a subgroup of individuals with psychosis. Whether these patients with elevated peripheral inflammation demonstrate deficits in specific cognitive domains remains unclear. To examine this, seventeen neuropsychological and sensorimotor tasks and thirteen peripheral inflammatory and microvascular markers were quantified in a subset of B-SNIP consortium participants (129 psychosis, 55 healthy controls). Principal component analysis was conducted across the inflammatory markers, resulting in five inflammation factors. Three discrete latent cognitive domains (Visual Sensorimotor, General Cognitive Ability, and Inhibitory Behavioral Control) were characterized based on the neurobehavioral battery and examined in association with inflammation factors. Hierarchical clustering analysis identified cognition-sensitive high/low inflammation subgroups. Among persons with psychotic disorders but not healthy controls, higher inflammation scores had significant associations with impairments of Inhibitory Control (R² = 0.100, p-value = 2.69e^-4, q-value = 0.004) and suggestive associations with Visual Sensorimotor function (R² = 0.039, p-value = 0.024, q-value = 0.180), but not with General Cognitive Ability (R² = 0.015, p-value = 0.162). Greater deficits in Inhibitory Control were observed in the high inflammation patient subgroup, which represented 30.2 % of persons with psychotic disorders, as compared to the low inflammation psychosis subgroup. These findings indicate that inflammation dysregulation may differentially impact specific neurobehavioral domains across psychotic disorders, particularly performance on tasks requiring ongoing behavioral monitoring and control.

Keywords: Bipolar disorder with psychotic features; Cognition; Inflammation; Schizoaffective disorder; Schizophrenia.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Behavior Control
Bipolar Disorder*
Humans
Inflammation / complications
Neuropsychological Tests
Psychotic Disorders*
Schizophrenia*

Abstract

Publication types

MeSH terms

Grants and funding