Patterns of Immune Dysregulation in Bipolar Disorder

Benney M R Argue; Lucas G Casten; Shaylah McCool; Aysheh Alrfooh; Jenny Gringer Richards; John A Wemmie; Vincent A Magnotta; Aislinn J Williams; Jacob Michaelson; Jess G Fiedorowicz; Sabrina M Scroggins; Marie E Gaine

doi:10.1101/2024.07.26.24311078

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Patterns of Immune Dysregulation in Bipolar Disorder

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Patterns of Immune Dysregulation in Bipolar Disorder

Benney M R Argue, Lucas G Casten, Shaylah McCool, Aysheh Alrfooh, Jenny Gringer Richards, John A Wemmie, Vincent A Magnotta, Aislinn J Williams, Jacob Michaelson, Jess G Fiedorowicz, …

medRxiv : the preprint server for health sciences

Cold Spring Harbor Laboratory

07/27/2024

DOI: 10.1101/2024.07.26.24311078

PMCID: PMC11361205

PMID: 39211848

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Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Bipolar disorder is a debilitating mood disorder associated with a high risk of suicide and characterized by immune dysregulation. In this study, we used a multi-faceted approach to better distinguish the pattern of dysregulation of immune profiles in individuals with BD.BackgroundBipolar disorder is a debilitating mood disorder associated with a high risk of suicide and characterized by immune dysregulation. In this study, we used a multi-faceted approach to better distinguish the pattern of dysregulation of immune profiles in individuals with BD.We analyzed peripheral blood mononuclear cells (bipolar disorder N=39, control N=30), serum cytokines (bipolar disorder N=86, control N=58), whole blood RNA (bipolar disorder N=25, control N=25), and whole blood DNA (bipolar disorder N=104, control N=66) to identify immune-related differences in participants diagnosed with bipolar disorder compared to controls.MethodsWe analyzed peripheral blood mononuclear cells (bipolar disorder N=39, control N=30), serum cytokines (bipolar disorder N=86, control N=58), whole blood RNA (bipolar disorder N=25, control N=25), and whole blood DNA (bipolar disorder N=104, control N=66) to identify immune-related differences in participants diagnosed with bipolar disorder compared to controls.Flow cytometry revealed a higher proportion of monocytes in participants with bipolar disorder together with a lower proportion of T helper cells. Additionally, the levels of 18 cytokines were significantly elevated, while two were reduced in participants with bipolar disorder. Most of the cytokines altered in individuals with bipolar disorder were proinflammatory. Forty-nine genes were differentially expressed in our bipolar disorder cohort and further analyses uncovered several immune-related pathways altered in these individuals. Genetic analysis indicated variants associated with inflammatory bowel disease also influences bipolar disorder risk.ResultsFlow cytometry revealed a higher proportion of monocytes in participants with bipolar disorder together with a lower proportion of T helper cells. Additionally, the levels of 18 cytokines were significantly elevated, while two were reduced in participants with bipolar disorder. Most of the cytokines altered in individuals with bipolar disorder were proinflammatory. Forty-nine genes were differentially expressed in our bipolar disorder cohort and further analyses uncovered several immune-related pathways altered in these individuals. Genetic analysis indicated variants associated with inflammatory bowel disease also influences bipolar disorder risk.Our findings indicate a significant immune component to bipolar disorder pathophysiology and genetic overlap with inflammatory bowel disease. This comprehensive study supports existing literature, whilst also highlighting novel immune targets altered in individuals with bipolar disorder. Specifically, multiple lines of evidence indicate differences in the peripheral representation of monocytes and T cells are hallmarks of bipolar disorder.DiscussionOur findings indicate a significant immune component to bipolar disorder pathophysiology and genetic overlap with inflammatory bowel disease. This comprehensive study supports existing literature, whilst also highlighting novel immune targets altered in individuals with bipolar disorder. Specifically, multiple lines of evidence indicate differences in the peripheral representation of monocytes and T cells are hallmarks of bipolar disorder.

Details

Title: Subtitle: Patterns of Immune Dysregulation in Bipolar Disorder
Creators: Benney M R Argue - University of Iowa
Lucas G Casten - University of Iowa, Psychiatry
Shaylah McCool - University of Iowa
Aysheh Alrfooh - University of Iowa
Jenny Gringer Richards
John A Wemmie - University of Iowa, Iowa Neuroscience Institute
Vincent A Magnotta - University of Iowa, Iowa Neuroscience Institute
Aislinn J Williams - University of Iowa, Iowa Neuroscience Institute
Jacob Michaelson - University of Iowa, Iowa Neuroscience Institute
Jess G Fiedorowicz - University of Iowa, Psychiatry
Sabrina M Scroggins - University of Minnesota System
Marie E Gaine - University of Iowa, Iowa Neuroscience Institute
Resource Type: Preprint
Publication Details: medRxiv : the preprint server for health sciences
DOI: 10.1101/2024.07.26.24311078
PMID: 39211848
PMCID: PMC11361205
Publisher: Cold Spring Harbor Laboratory
Language: English
Date posted: 07/27/2024
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Radiology; Communication Sciences and Disorders; Molecular Physiology and Biophysics; Psychiatry; Epidemiology; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Neurosurgery
Record Identifier: 9984720460102771

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