Genes, Cognition, and Their Interplay in Methamphetamine Use Disorder.

Abstract

Methamphetamine use disorder is a pressing global health issue, often accompanied by significant cognitive deficits that impair daily functioning and quality of life and complicate treatment. Emerging evidence highlights the potential role of genetic factors in methamphetamine use disorder, particularly in association with cognitive function. This review examines the key genetic and cognitive dimensions and their interplay in methamphetamine use disorder. There is converging evidence from several studies that genetic polymorphisms in BDNF, FAAH, SLC18A1, and SLC18A2 are associated with protection against or susceptibility to the disorder. In addition, people with methamphetamine use disorder consistently displayed impairments in cognitive flexibility and inhibitory control compared with people without the disorder. These cognitive domains were associated with reactivity to methamphetamine cues that were positively correlated with total years of methamphetamine use history. Emerging research also suggests that inhibitory control is negatively correlated with lower blood FAAH mRNA levels, while cognitive flexibility positively correlates with higher blood SLC18A2 mRNA levels, highlighting how genetic and cognitive dimensions interact in methamphetamine use disorder. We also include some future directions, emphasizing potential personalized therapeutic strategies that integrate genetic and cognitive insights. By drawing attention to the interplay between genes and cognition, we hope to advance our understanding of methamphetamine use disorder and inform the development of targeted interventions.