Decreased plasma concentrations of BDNF and IGF-1 in abstinent patients with alcohol use disorders

Abstract

The identification of growth factors as potential biomarkers in alcohol addiction may help to understand underlying mechanisms associated with the pathogenesis of alcohol use disorders (AUDs). Previous studies have linked growth factors to neural plasticity in neurocognitive impairment and mental disorders. In order to further clarify the impact of chronic alcohol consumption on circulating growth factors, a cross-sectional study was performed in abstinent AUD patients (alcohol group, N = 91) and healthy control subjects (control group, N = 55) to examine plasma concentrations of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1) and IGF-1 binding protein-3 (IGFBP-3). The association of these plasma peptides with relevant AUD-related variables and psychiatric comorbidity was explored. The alcohol group was diagnosed with severe AUD and showed an average of 13 years of problematic use and 10 months of abstinence at the moment of participating in the study. Regarding common medical conditions associated with AUD, we observed an elevated incidence of alcohol-induced liver and pancreas diseases (18.7%) and psychiatric comorbidity (76.9%). Thus, AUD patients displayed a high prevalence of dual diagnosis (39.3%) [mainly depression (19.9%)] and comorbid substance use disorders (40.7%). Plasma BDNF and IGF-1 concentrations were significantly lower in the alcohol group than in the control group (p<0.001). Remarkably, there was a negative association between IGF-1 concentrations and age in the control group (r = -0.52, p<0.001) that was not found in the alcohol group. Concerning AUD-related variables, AUD patients with liver and pancreas diseases showed even lower concentrations of BDNF (p<0.05). In contrast, the changes in plasma concentrations of these peptides were not associated with abstinence, problematic use, AUD severity or lifetime psychiatric comorbidity. These results suggest that further research is necessary to elucidate the role of BDNF in alcohol-induced toxicity and the biological significance of the lack of correlation between age and plasma IGF-1 levels in abstinent AUD patients.

Alcohol‐induced cognitive deficits are associated with decreased circulating levels of the neurotrophin BDNF in humans and rats

“…DSM‐IV‐TR criteria for substance dependence and abuse were used to diagnose substance use disorders and determine the severity of substance use disorders (García‐Marchena et al . ).…”

“…Blood samples were obtained in the morning (9:00–11:00 am ) after fasting for 8–12 hours (previous to the psychiatric interviews), as described previously (García‐Marchena et al . ). Plasma samples were individually characterized, registered and stored at −80°C until further analyses.…”

“…As described previously (García‐Marchena et al . ), plasma concentrations of total IGF‐1 were estimated by double antibody radioimmunoassay. Plasma fractions were incubated with 125 I‐IGF‐1 at 4°C for 24 hours.…”

“…Chronic alcohol exposure can reduce the circulating concentration of the neurotrophin BDNF, and this effect was more pronounced in AUD patients with alcohol‐induced liver and/or pancreas diseases (García‐Marchena et al . ). Despite previous clinical studies suggested a deregulation of BDNF in patients with neuropsychiatric disorders (schizophrenia, depression and anxiety), such association was not found in that study, where cognitive impairment was not evaluated (Bocchio‐Chiavetto et al .…”

Differential Correlation of Serum BDNF and microRNA Content in Rats with Rapid or Late Onset of Heavy Alcohol Use

“…Interestingly, a number of reports suggest that circuiting BDNF levels are inversely correlated with the severity of psychiatric disorders (Cattaneo et al, 2016). Similarly, humans with AUD have reduced serum BDNF content compared to healthy controls (Heberlein et al, 2010;Nubukpo et al, 2017;Silva-Pena et al, 2019;Zanardini et al, 2011;Zhou et al, 2018), which are still detected in abstinent alcoholics (Garcia-Marchena et al, 2017). Lower BDNF content has also been correlated with greater reported alcohol withdrawal severity in alcoholics (Costa et al, 2011;Heberlein et al, 2010).…”