C-reactive protein concentrations diverge as a function of substance use disorder: A pre-registered replication in a clinical sample

Jennifer L Stewart; Kaiping Burrows; April C May; Breanna A McNaughton; Ryan Smith; Rayus Kuplicki; Martin P Paulus; Leandra Figueroa-Hall

doi:10.1016/j.drugalcdep.2024.111323

C-reactive protein concentrations diverge as a function of substance use disorder: A pre-registered replication in a clinical sample

Drug Alcohol Depend. 2024 May 8:260:111323. doi: 10.1016/j.drugalcdep.2024.111323. Online ahead of print.

Authors

Jennifer L Stewart¹, Kaiping Burrows², April C May³, Breanna A McNaughton², Ryan Smith⁴, Rayus Kuplicki², Martin P Paulus⁴, Leandra Figueroa-Hall⁴

Affiliations

¹ Laureate Institute for Brain Research, Tulsa, OK, USA; Oxley College of Health Sciences, The University of Tulsa, Tulsa, OK, USA. Electronic address: jstewart@laureateinstitute.org.
² Laureate Institute for Brain Research, Tulsa, OK, USA.
³ School of Medicine, Stanford University, Palo Alto, CA, USA.
⁴ Laureate Institute for Brain Research, Tulsa, OK, USA; Oxley College of Health Sciences, The University of Tulsa, Tulsa, OK, USA.

PMID: 38733735
DOI: 10.1016/j.drugalcdep.2024.111323

Abstract

Background: Inflammatory biomarkers may differentiate clinical disorders, which could lead to more targeted interventions. Analyses within a clinical sample (May et al., 2021) revealed that females with substance use disorders (SUD) exhibited lower C-reactive protein (CRP) and higher interleukin (IL)-8 and -10 concentrations than females without SUD who met criteria for mood/anxiety disorders. We aimed to replicate these findings in a new sample.

Methods: Hypotheses and analyses were preregistered. Treatment-seeking individuals with mood/anxiety disorders and/or SUD (N = 184) completed a blood draw, clinical interview, and questionnaires. Participants were categorized as SUD+ (45F, 43M) and SUD- (78F, 18M). Principal component analysis (PCA) of questionnaire data resulted in two factors reflecting appetitive and aversive emotional states. SUD group and nuisance covariates (PCA factors, age, body mass index [BMI], medication, nicotine [and hormones in females]) predicted biomarker concentrations (CRP, IL-8, and IL-10) in regressions.

Results: In females, the omnibus CRP model [F(8, 114) = 8.02, p <.001, R²-adjusted =.32] indicated that SUD+ exhibited lower CRP concentrations than SUD- (β = -.33, t = -3.09, p =.002, 95% CI [-.54, -.12]) and greater BMI was associated with higher CRP levels (β =.58, t = 7.17, p <.001, 95% CI [.42,.74]). SUD+ exhibited higher IL-8 levels than SUD- in simple but not omnibus regression models.

Conclusion: Findings across two samples bolster confidence that females with SUD show attenuated CRP-indexed inflammation. As SUD+ comorbidity was high, replication is warranted with respect to specific SUD classes (i.e., stimulants versus cannabis).

Keywords: C-reactive protein; Cytokines; Inflammation; Substance use disorder.