A composite immune and vascular stress marker in patients newly diagnosed with bipolar disorder and their unaffected first-degree relatives

Klara Coello*, Helle Holstad Pedersen, Klaus Munkholm, Hanne Lie Kjærstad, Sharleny Stanislaus, Sisse Rye Ostrowski, Maria Faurholt-Jepsen, Kamilla Woznica Miskowiak, Ruth Frikke-Schmidt, Maj Vinberg, Claus Thorn Ekstrøm, Julie Lyng Forman, Lars Vedel Kessing

*Corresponding author for this work
1 Citation (Scopus)

Abstract

AIMS: Substantial evidence emphasizes immune dysregulation in patients with bipolar disorder (BD). However, whether immune dysregulation is present already in the early illness stages of BD or even precedes development of BD is largely unknown. In this study we compared immune and vascular stress markers in patients newly diagnosed with BD, their unaffected first-degree relatives (UR) and healthy control individuals (HC) and investigated the ability a composite immune and vascular stress marker to discriminate between the three groups of participants.

METHODS: In a unique sample including 373 patients newly diagnosed with BD, 95 UR and 190 HC, we compared 47 immune and vascular stress markers at the baseline visit in the ongoing longitudinal Bipolar Illness Onset study. For comparison of individual immune and vascular stress markers between groups, we applied linear mixed models, whereas the composite immune and vascular stress marker was investigated using the SuperLearner ensemble-method.

RESULTS: Compared with HC, patients newly diagnosed with BD had higher levels of the anti-inflammatory interleukin-1 receptor antagonist (IL-1RA) and IL-10, and of the pro-inflammatory IL-6, eotaxin, monocyte chemoattractant protein-1 (MCP-1), MCP-4, Macrophage Derived Chemokine (MDC), and Thymus and Activation-Regulated Chemokine (TARC) in analyses adjusted for sex and age ranging from 26 % higher levels of IL-6 (1.26, 95 %CI: [1.12-1.43], p < 0.001, adjusted p = 0.009) and IL-10 (1.26, 95 %CI: [1.09-1.46], p = 0.002, adjusted p = 0.049), respectively, to 9 % higher eotaxin levels (1.09, 95 %CI: [1.04-1.15], p = 0.001, adjusted p = 0.024). Of these, MDC levels were 12 % higher in BD compared with UR (1.12, 95 %CI: [1.02-1.22], p = 0.001, adjusted p = 0.024). For all other markers, UR showed no difference from patients with BD or HC. Based on a data-driven model, a composite marker including all 47 immune and vascular stress markers, sex, age, BMI, smoking status, and alcohol intake, discriminated patients with BD from HC with a with an area under the receiver operating curve (AUC) of 0.76 (95 % CI: 0.75-0.77) CONCLUSIONS: Higher levels of pro-inflammatory and anti-inflammatory immune markers are present in patients newly diagnosed with BD but not in UR compared with HC, supporting immune dysregulation playing a role in the pathophysiology of BD.

Original languageEnglish
JournalBrain, Behavior, and Immunity
Volume118
Pages (from-to)449-458
Number of pages10
ISSN0889-1591
DOIs
Publication statusPublished - May 2024

Keywords

  • Bipolar Disorder
  • Immune dysregulation
  • Immune markers
  • Inflammation
  • Newly Diagnosed
  • Unaffected Relatives
  • Vascular stress

Fingerprint

Dive into the research topics of 'A composite immune and vascular stress marker in patients newly diagnosed with bipolar disorder and their unaffected first-degree relatives'. Together they form a unique fingerprint.

Cite this