Journal article
Immune dysregulation in bipolar disorder
Journal of affective disorders, Vol.374, pp.587-597
04/2025
DOI: 10.1016/j.jad.2025.01.062
PMCID: PMC11830520
PMID: 39818340
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.
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.
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.
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.
Details
- Title: Subtitle
- Immune dysregulation in bipolar disorder
- Creators
- Benney M R Argue - University of IowaLucas G Casten - University of IowaShaylah McCool - University of IowaAysheh Alrfooh - University of IowaJenny Gringer Richards - University of IowaJohn A Wemmie - University of IowaVincent A Magnotta - University of IowaAislinn J Williams - University of IowaJacob Michaelson - University of IowaJess G Fiedorowicz - University of OttawaSabrina M Scroggins - University of Minnesota, DuluthMarie E Gaine - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of affective disorders, Vol.374, pp.587-597
- DOI
- 10.1016/j.jad.2025.01.062
- PMID
- 39818340
- PMCID
- PMC11830520
- NLM abbreviation
- J Affect Disord
- ISSN
- 0165-0327
- eISSN
- 1573-2517
- Publisher
- ELSEVIER
- Grant note
- National Institutes of Health through a Predoctoral Training Grant: NCATS 3UL1TR002537-03W1, NHLBI 1KO1HL155240-01, NCATS UL1TR002494
This study was supported by an Iowa Neuroscience Institute Research Program of Excellence grant with philanthropy from the Roy J. Carver Charitable Trust (JAW) , a U.S. Department of Veterans Affairs Merit Review Award (JAW) and a U.S. Department of Veterans Affairs Senior Clinician Scientist (JAW) . It was also supported by an EHSRC Career Enhancement award and an EHSRC Pilot grant (NIH P30 ES005605; MEG) and by the National Center for Advancing Translational Sciences of the National Institutes of Health (UL1TR002537) and the National Institute of Mental Health (NIMH R01MH125838 and R01MH111578 to VAM and JAW) . Funding for this work was given to SS through the OB/GYN department at the University of Iowa Hospitals & Clinics, as well as the AHA with grant 19IPLOI34760288, and the NIH with grants NCATS 3UL1TR002537-03W1, NHLBI 1KO1HL155240-01, and NCATS UL1TR002494. Additional funding for this work came from the National Institutes of Health through a Predoctoral Training Grant (T32GM008629 to LGC) .r with grants NCATS 3UL1TR002537-03W1, NHLBI 1KO1HL155240-01, and NCATS UL1TR002494. Additional funding for this work came from the National Institutes of Health through a Predoctoral Training Grant (T32GM008629 to LGC) .
- Language
- English
- Electronic publication date
- 01/14/2025
- Date published
- 04/2025
- 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
- 9984774239102771
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