Estimation of BDNF gene polymorphism and predisposition to dependence development for selected psychoactive compounds

Abstract

The etiology of drug addiction, a central nervous system (CNS) disease, is not fully known. This complex problem is believed to be connected with concurrently affecting genetic, psychological and environmental factors. The development of addiction is connected with CNS reinforcement system and dopaminergic neurotransmission. Molecular processes are postulated to be of universal character and allow to presume a similar mechanism of dependence for both ethanol and other substances. Therefore, elements of dopaminergic transmission become excellent candidates for the examination of genetic influence on the development of addiction. A relationship between alcoholic disease and the presence of TaqIA1 and DRD2 alleles permits to initiate another investigation of gene-coding DRD2 dopamine receptor. The latest results indicate the importance of brain-derived neurotrophic factor (BDNF) in the regulation of dopaminergic route. The purpose of this research was to reveal the relationship between the Val66Met BDNF gene polymorphism and dependence of psychoactive agent. The examinations were performed with the Local Research Ethics Committee approval and patient's consent. The study group consisted of 100 patients (88 men and 12 women) aged 18-52 years, qualified for research program according to the International Classification of Diseases, Tenth Revision (ICD-10) requirements, medical examination and detailed questionnaire.

The BDNF Valine 68 to Methionine Polymorphism Increases Compulsive Alcohol Drinking in Mice That Is Reversed by Tropomyosin Receptor Kinase B Activation

“…Val66 to Met substitution substantially alters the intracellular trafficking of the immature form of BDNF and decreased activity-dependent release of the neurotrophic factor (20, 21). The Met66BDNF polymorphism is relatively common in humans (22), and has been associated with increased severity of psychiatric disorders (23–25) including addiction to nicotine, opiates, amphetamine and tetrahydrocannabinol (26–28). We hypothesized that subjects carrying the Met66BDNF allele will be at greater risk of developing “pathological” excessive alcohol drinking behaviors.…”

Mice engineered to mimic a common Val66Met polymorphism in the BDNF gene show greater sensitivity to reversal in environmental contingencies

“…The Met substitution at this codon confers a trafficking deficit which results in decreased activity dependent release of BDNF (Chen et al, 2006). This polymorphism occurs in 20–30% of the human population and has been linked to deficits in select forms of memory (Egan et al, 2003), as well as susceptibility to psychiatric disorders (Angelucci et al, 2005; Chen et al, 2006; Frielingsdorf et al, 2010; Gratacos et al, 2007; Joffe et al, 2009), including substance abuse (Cheng et al, 2005; Duncan, 2012; Biskupska et al, 2013; Greenwald et al, 2013). Differences in activity dependent release of BDNF may alter the time course or trajectory of neural circuit development by many routes (Bath and Lee, 2006; Pattwell et al, 2012; Vandenberg et al, 2015; Wang et al, 2015; Jing et al, 2017).…”

Microbiome: The Next Frontier in Psychedelic Renaissance

“…Another aspect contributing to interpersonal variability is genetic predisposition [ 55 , 66 ]. It is well established that genetic factors may influence the metabolism of various substances, including psychedelics, and this can potentially affect their pharmacokinetics and pharmacodynamics.…”

“…For instance, polymorphisms in enzymes involved in the metabolism of psychedelic substances, such as monoamine oxidases and cytochrome P450 enzymes, can lead to differences in the metabolism rate among individuals, thereby affecting the substances' bioavailability and effects [67]. Another aspect contributing to interpersonal variability is genetic predisposition [55,66]. It is well established that genetic factors may influence the metabolism of various substances, including psychedelics, and this can potentially affect their pharmacokinetics and pharmacodynamics.…”