Altered Expression of Neuroplasticity-Related Genes in Alcohol Addiction and Treatment

Abstract

Alcohol use disorder's complexity arises from genetic and environmental factors, with alcohol metabolism genes and neurotransmitter pathways being critical. This study aims to analyze synaptic plasticity gene expression changes in individuals with AUD in order to study their contribution to AUD development and to identify potential biomarkers of treatment response. RNA was extracted from whole peripheral blood (20 patients, 10 healthy controls), before and after treatment (Qiagen AllPrep RNA/DNA Mini Kit), and the gene expression of 84 genes related to neuroplasticity was studied using the RT2 Profiler for Human Synaptic Plasticity RT-PCR Array (PAHS-126ZA, Qiagen), comparing AUD patients to control and responders to non-responders. The potential prognostic/predictive biomarkers were searched using machine learning models. A total of 35 dysregulated genes were found in AUD patients. EPHB2, EGR, and AKT1 were increased, while TIMP1, NCAM1, and GRM2 were decreased. Responders showed distinct gene expression profiles at baseline. After treatment, the expression of 57 genes was normalized, while NCAM1, GRM2, and BDNF showed the most significant recovery. EGR4, INHBA, and NCAM1 emerged as potential biomarkers to predict treatment success. These results indicate that gene profiles in peripheral blood can serve as prognostic markers for the prognosis and treatment of AUD, although further validation is required.

Keywords: alcohol use disorder (AUD); biomarker; gene expression; neuroplasticity; synaptic plasticity.

Figure 1

Differential expression of synaptic plasticity-related genes in alcohol use disorder (AUD) versus healthy controls. Box plots representing the fold regulation of 35 synaptic plasticity-related genes in AUD patients compared to healthy controls. Gene expression was transformed to log₂(1/ΔCt) values for visualization.

Figure 2

Co-expression analysis of synaptic plasticity-related genes in healthy controls and alcoholics. Spearman correlation heatmaps for synaptic plasticity-related genes in healthy controls (left) and alcoholics (right). Results filtered for rho less than −0.8 and greater than 0.8.

Figure 3

Baseline gene expression differences between responders and non-responders to alcohol detoxification therapy. Box plots representing the fold regulation of 15 synaptic plasticity-related genes. Gene expression was transformed to log₂(1/ΔCt) values for visualization. These gene expression profiles suggest potential biomarkers that could predict therapeutic response in AUD patients.

Figure 4

Correlation matrix of synaptic plasticity-related genes in responders versus non-responders to alcohol detoxification therapy. Spearman correlation heatmaps for synaptic plasticity-related genes in responders (left) and non-responders (right) to therapy. Responders show limited co-expression between gene pairs, while non-responders exhibit a more extensive and complex gene interaction network, suggesting that non-responders may have more widespread dysregulation in synaptic plasticity-related pathways. Results filtered for rho less than −0.8 and greater than 0.8.

Figure 5

Gene expression changes before and after alcohol detoxification therapy in responders. Box plots representing the fold regulation of 57 synaptic plasticity-related genes. Gene expression was transformed to log₂(1/ΔCt) values for visualization. Previously upregulated genes such as EGR4, EPHB2, and HOMER1 are downregulated after therapy, suggesting a reversal of alcohol-induced dysregulation.

Figure 6

Correlation matrix of synaptic plasticity-related genes before and after alcohol detoxification therapy in responders. Spearman correlation heatmaps for synaptic plasticity-related genes in responders before (left) and after (right) therapy. The therapy appears to restore the balance in synaptic plasticity-related gene expression, as evidenced by the reduction in co-expression patterns. Results filtered for rho less than −0.8 and greater than 0.8.