Peripheral proinflammatory markers are upregulated in abstinent alcohol-dependent patients but are not affected by cognitive bias modification: Preliminary findings

Abstract

Background: Inflammatory pathways are known to be negatively affected in patients with alcohol use disorder (AUD). Cognitive bias modification (CBM), an emerging behavioral treatment that involves the 're-training' of cognitive biases using computerized tasks, has been reported to reduce alcohol craving and relapse rates. The aim of this study was to compare peripheral concentrations of the proinflammatory biomarkers IL-18, IL-6, IL-1β, TNF-α and CRP in AUD patients versus controls and to identify whether CBM treatment affected these biomarkers in AUD patients.

Methods: This 3-week double-blind randomized controlled study tested 36 male abstinent AUD patients receiving CBM or placebo-training, who were also compared to 18 male healthy controls. The approach avoidance task (AAT) was used to test the AUD patients before and after training. CBM training took place over 6 sessions, using a joystick-based approach-avoidance task. Blood samples were collected after the pre- and post-AAT test sessions for the AUD groups, and during an outpatient appointment with the controls.

Results: AUD patients, versus controls, presented with significantly higher plasma levels of TNF- α (P < 0.0001) and CRP (P = 0.0031). No changes in the CBM versus placebo groups were noted in IL-18, TNF-α and CRP concentrations following pre-post change or within group pretest- posttest analysis. IL-6 and IL-1β levels fell under the lower detection limit, thus were not included in the final analyses.

Conclusions: This study confirms that the inflammatory system is altered in AUD. This was the first study that investigated whether CBM training affected proinflammatory markers in AUD patients.

Keywords: Alcohol use disorder; C-Reactive protein; Cognitive bias modification; Inflammation; Interleukin-18; Tumor necrosis factor-a.

Figure 1:

Plasma concentrations of pro-inflammatory markers in the healthy control group and AUD patient group. A) Plasma IL-18 concentrations in pg/ml (Healthy controls: n = 18; AUD group: n = 31); B) Plasma TNF-α concentrations in pg/ml (Healthy controls: n= 16; AUD group: n = 31); C) Plasma CRP concentrations in mg/L (Healthy controls: n = 18; AUD group: n = 28). Individual data points of participants were plotted with the calculated median with 95% confidence interval (CI). ** indicates P < 0.01, **** indicates P < 0.0001 (Wilcoxon ranked sum test). AUD = alcohol use disorder; IL-18 = interleukin 18; TNF-α = tumor necrosis factor alpha; CRP = C-reactive protein

Figure 2:

Plasma concentrations of pro-inflammatory markers before and after CBM and Placebo treatment in AUD participants. A) Plasma IL-18 concentrations in pg/ml (Pre-CBM: n = 16; Post-CBM: n = 16; Pre-placebo: n = 12; Post-placebo: n = 12); B) Plasma TNF-α concentrations in pg/ml (Pre-CBM: n = 16; Post-CBM: n = 16; Pre-placebo: n = 12; Post-placebo: n = 12); C) Plasma CRP concentrations in mg/L (Pre-CBM: n = 13; Post-CBM: n = 13; Pre-placebo: n = 11; Post-placebo: n = 11). Individual data points of participants were plotted with the calculated median with 95% confidence interval (CI) CBM = cognitive bias modification; AUD = alcohol use disorder; IL-18 = interleukin 18; TNF-α = tumor necrosis factor alpha; CRP = C-reactive protein