EXPLORE THE ROLE OF GROWTH FACTOR FGF2 IN ALCOHOL DEPENDENCE

Abstract Background Although several growth factors have been implicated in alcohol dependence (AD) [1], fibroblast growth factor 2 (FGF2) was hypothesized to play a role in an endogenous pathway contributing to the transition from moderate to excessive alcohol use in the development of AD. In this study, the FGF2 was further investigated for its association with a brain injury indicator, neurofilament light chain (NFL) [2], and inflammatory factor, C-C-motif chemokine ligand 11 (CCL11), to assess its role in AD and delirium tremens (DT). Aims & Objectives In our previous report, a significant increase in CCL11 [3] and NFL [4] levels in was observed in patients with AD. Expanding on the results, we further examined the role of FGF2 in this cohort of AD patients. Method A total of 224 AD patients and 117 non-AD reference controls were examined in this study. Their plasma NFL were measured using the parallel Simple Plex NFL Assay via the Ella instrument, following the manufacturers’ instructions. Additionally, their CCL11 and FGF2 levels were measured by Enzyme-linked Immunosorbent Assay (ELISA). Statistical analyses included the Mann-Whitney U test for comparing two groups, and Spearman's correlation analysis for assessing bivariate correlations. The receiver operating characteristic (ROC) curve was plotted to identify the area under the curve (AUC) for the levels of plasma FGF2, CCL11 and NFL in controls and patients with AD, or in those with DT and without DT (DT vs non-DT group). Results The age and gender were matched between AD and controls. Plasma FGF2, CCL11 and NFL were significantly increased in AD patients (Mann-Whitney U test, all P< 0.0001), and the prediction for AD were high for NFL (AUC = 0.75) and CCL11 (AUC = 0.73), but low for FGF2 (AUC = 0.63). When categorizing into DT and non-DT among AD patients, the DT group was older in age compared with non- DT or control group. The rank order in prediction of DT from non-DT was NFL (AUC = 0.83) >CCL11 (AUC = 0.59)> FGF2 (AUC = 0.54). Furthermore, a subset of DT group, who self-reported a history of DT (HDT) in the past, exhibited an elevated FGF2 level than the control group (P=0.036). FGF2 levels were negatively correlated with CCL11 levels (Spearman’ s r=-0.167, P=0.031). Discussion & Conclusion These results indicated that FGF2 may be function as an intermediate growth factor within the pathological pathway of AD. Compared to NFL and CCL11, FGF2 is less satisfactory to discriminate AD from controls or DT from non-DT. It exhibited a negative correlation with plasma CCL11 levels, suggesting potential role in the regulatory mechanisms. References 1.Liran, M., et al., Growth Factors and Alcohol Use Disorder. Cold Spring Harb Perspect Med, 2020. 10 (12): p. a039271. Khalil, M., et al., Neurofilaments as biomarkers in neurological disorders. Nature Reviews Neurology, 2018. 14(10): p. 577-589. 2.Huang, M.C., et al., Increase in plasma CCL11 (Eotaxin-1) in patients with alcohol dependence and changes during detoxification. Brain Behav Immun, 2022. 99: p. 83-90. 3.Huang, M.C., et al., Changes of neurofilament light chain in patients with alcohol dependence following withdrawal and the genetic effect from ALDH2 Polymorphism. Eur Arch Psychiatry Clin Neurosci, 2023.