Biobehavioural assessment of methamphetamine use disorder: an interplay between genes, cognition, and duration of drug use — The Association Specialists
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Biobehavioural assessment of methamphetamine use disorder: an interplay between genes, cognition, and duration of drug use (21651)

Alexandre Guerin 1 , Briana Spolding 2 , Kiymet Bozaoglu 1 , Courtney Swinton 2 , Zoe Liu 2 , Bruna Parry 2 , Trang Truong 2 , Brian Dean 3 , Andrew Lawrence 3 , Yvonne Bonomo 4 , Eric Nestler 5 , Peter Hamilton 5 , Michael Berk 2 , Susan Rossell 6 , Ken Walder 2 , Jee Hyun Kim 2
  1. The University of Melbourne, Parkville
  2. Medicine, IMPACT, Deakin University, Geelong
  3. Florey Department of Neuroscience and Mental Health, University of Melbourne, Parkville
  4. St Vincent's Hospital, Fitzroy
  5. Icahn School of Medicine at Mt Sinai, New york
  6. Swinburne University of Technology, Hawthorn

Background:  A range of risk factors are associated with the development of methamphetamine use disorder, including genetics. Assessing sequence variations and expression of candidate genes can help understand the disorder and inform potential treatments. This study is an investigation of single nucleotide polymorphisms and gene expression in four candidate genes: SLC18A1, SLC18A2, BDNF, and FAAH, between controls and people with methamphetamine use disorder.

Method: Fifty-nine participants (29 people with methamphetamine use disorder and 30 controls) completed a clinical interview, cognitive tasks, and provided a blood sample. SLC18A1, SLC18A2, BDNF, and FAAH single nucleotide polymorphisms were genotyped, and gene expression was assessed with real-time quantitative PCR.

Results: SLC18A1 Pro4Thr was associated with methamphetamine use disorder (OR = 6.22; p = 0.007). SLC18A2 variants, rs363227 and rs363387, were negatively associated with severity of methamphetamine dependence (p = 0.003) and positively associated with inhibitory control performance (p = 0.006), respectively. BDNF Val66Met was associated with severity of dependence (p = 0.008). SLC18A2 and FAAH blood mRNA levels were lower in people who use methamphetamine relative to controls (p = 0.021 and 0.010, respectively).

Conclusions: SLC18A1, which codes for the vesicular monoamine transporter 1 (VMAT1), is identified for the first time to play a potential role in conferring a risk for methamphetamine use disorder. Lower levels of blood SLC18A2 and FAAH mRNA in people with methamphetamine use disorder suggest reduced monoamine reuptake, recycling, or release and higher anandamide levels in this clinical group, which may be potential therapeutic targets.