BDNF gene polymorphisms and substance use disorders: a systematic review

The development of substance use disorders (SUDs) is partly determined by genetic factors. Brain-derived neurotrophic factor (BDNF) underlies the neurobiological mechanisms of action of psychoactive substances (PASs) and development of SUDs, while genetic markers within the BDNF gene may be associated with a risk of SUDs and accompanied clinical manifestations. This is a systematic review of the relationships between single nucleotide polymorphisms (SNPs) within the BDNF gene locus and various aspects of SUDs. We searched, appraised, and summarized the research evidence of these associations for the main pharmacological groups of PASs (tobacco, cannabis, alcohol, opioids, and stimulants). Most studies have focused on the functional Val66Met (rs6265) polymorphism. They demonstrated that the rs6265 Met (T) allele may be a protective factor for the development of SUDs. In addition to rs6265, other individual BDNF-related SNPs and the corresponding haplotypes were associated with the risk of the development of SUDs, their clinical manifestations, presence of comorbidity, and sensitivity to pharmacotherapy. The identified associations often depended on the studied population and were influenced by sex and ancestry. Established BDNF-related genetic markers or their combinations potentially may be used as objective diagnostic or prognostic criteria in clinical practice.