Genetics of methamphetamine use disorder: A systematic review and meta-analyses of gene association studies

Guerin, Alexandre A.; Nestler, Eric J.; Berk, Michael; Lawrence, Andrew J; Rossell, Susan L.; Kim, Jee Hyun

doi:10.1016/j.neubiorev.2020.11.001

Cited by 19 publications

(11 citation statements)

References 174 publications

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“…Changes in D1 and D2 expression did not appear to be associated with place conditioning with 3 mg/kg meth. This is consistent with recent meta-analyses showing that dopamine receptor gene polymorphisms may not determine risk towards meth use disorder [72]. Nevertheless, conditioning with meth altered insula D1 and D2 expression, which may subserve changes in behaviors commonly observed following meth use.…”

Section: Limitations and Future Directionssupporting

confidence: 90%

Insular cortex dopamine 1 and 2 receptors in methamphetamine conditioned place preference and aversion: Age and sex differences

Cullity

Guerin

Madsen

et al. 2021

Neuroanatomy and Behaviour

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Rodent studies have proposed that adolescent susceptibility to substance use is at least partly due to adolescents experiencing reduced aversive effects of drugs compared to adults. We thus investigated methamphetamine (meth) conditioned place preference/aversion (CPP/CPA) in adolescent and adult mice in both sexes using a high dose of meth (3 mg/kg) or saline as controls. Mice tagged with green-fluorescent protein (GFP) at Drd1a or Drd2 were used so that dopamine receptor 1 (D1) and 2 (D2) expression within the insular cortex (insula) could be quantified. There are sex differences in how the density of D1+ and D2+ cells in the insula changes across adolescence that may be related to drug-seeking behaviors. Immunohistochemistry followed by stereology were used to quantify the density of cells with c-Fos and/or GFP in the insula. Unexpectedly, mice showed huge variability in behaviors including CPA, CPP, or no preference or aversion. Females were less likely to show CPP compared to males, but no age differences in behavior were observed. Conditioning with meth increased the number of D2 + cells co-labelled with c-Fos in adults but not in adolescents. D1:D2 ratio also sex- and age-dependently changed due to meth compared to saline. These findings suggest that reduced aversion to meth is unlikely an explanation for adolescent vulnerability to meth use. Sex- and age-specific expressions of insula D1 and D2 are changed by meth injections, which has implications for subsequent meth use.

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Section: Limitations and Future Directionssupporting

confidence: 90%

Insular cortex dopamine 1 and 2 receptors in methamphetamine conditioned place preference and aversion: Age and sex differences

Cullity

Guerin

Madsen

et al. 2021

Neuroanatomy and Behaviour

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“…A variety of neurotransmitter and receptor system-related genes, including BDNF , DRD2 , and GABRB2 , were found to contain genetic variants that contribute to the vulnerability of METH use disorder ( 9 ). Although multiple lines of evidence have associated epigenetic alterations with METH dependence ( 25 , 26 ), no relevant population-based studies focusing on epigenetic-related genes have been conducted.…”

Section: Discussionmentioning

confidence: 99%

“…Numerous loci that influence complex traits, such as alcohol and other substance abuse, have been identified, facilitating our understanding of underlying molecular mechanisms ( 6 – 8 ). However, data on METH dependence remains scarce despite multiple reports of candidate genes ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

The Vulnerability to Methamphetamine Dependence and Genetics: A Case-Control Study Focusing on Genetic Polymorphisms at Chromosomal Region 5q31.3

Xiao

Wang

et al. 2022

Front. Psychiatry

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ObjectivesMethamphetamine (METH) is a central nervous psychostimulant and one of the most frequently used illicit drugs. Numerous genetic loci that influence complex traits, including alcohol abuse, have been discovered; however, genetic analyses for METH dependence remain limited. An increased histone deacetylase 3 (HDAC3) expression has been detected in Fos-positive neurons in the dorsomedial striatum following withdrawal after METH self-administration. Herein, we aimed to systematically investigate the contribution of HDAC3 to the vulnerability to METH dependence in a Han Chinese population.MethodsIn total, we recruited 1,221 patients with METH dependence and 2,328 age- and gender-matched controls. For genotyping, we selected 14 single nucleotide polymorphisms (SNPs) located within ± 3 kb regions of HDAC3. The associations between genotyped genetic polymorphisms and the vulnerability to METH dependence were examined by single marker- and haplotype-based methods using PLINK. The effects of expression quantitative trait loci (eQTLs) on targeted gene expressions were investigated using the Genotype-Tissue Expression (GTEx) database.ResultsThe SNP rs14251 was identified as a significant association signal (χ2 = 9.84, P = 0.0017). An increased risk of METH dependence was associated with the A allele (minor allele) of rs14251 [odds ratio (95% CI) = 1.25 (1.09–1.43)]. The results of in silico analyses suggested that SNP rs14251 could be a potential eQTL signal for FCHSD1, PCDHGB6, and RELL2, but not for HDAC3, in various human tissues.ConclusionWe demonstrated that genetic polymorphism rs14251 located at 5q31.3 was significantly associated with the vulnerability to METH dependence in Han Chinese population.

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“…Further, homozygous deletion of SERT in its knock-out mouse model shows a reduction of METH-induced locomotor activity and an increase in 5-HT levels ( Igari et al, 2015 ). A recent meta-analysis identified that functional variants of brain derived neurotrophic factor (BDNF) and fatty acid amide hydrolase (FAAH) are significantly associated with METH abuse disorder ( Guerin et al, 2021 ). This finding is relevant to neurotransmission, as a recent study found that BDNF plays a role mediating METH effects on serotonergic cells ( Sepulveda, Manning, Gogos, Hale, & van den Buuse, 2021 ).…”

Section: Methamphetaminementioning

confidence: 99%

Substance abuse and neurotransmission

Davis

Zhu

2022

Behavioral Pharmacology of Drug Abuse: Current Status

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Genetics of methamphetamine use disorder: A systematic review and meta-analyses of gene association studies

Cited by 19 publications

References 174 publications

Insular cortex dopamine 1 and 2 receptors in methamphetamine conditioned place preference and aversion: Age and sex differences

Insular cortex dopamine 1 and 2 receptors in methamphetamine conditioned place preference and aversion: Age and sex differences

The Vulnerability to Methamphetamine Dependence and Genetics: A Case-Control Study Focusing on Genetic Polymorphisms at Chromosomal Region 5q31.3

Substance abuse and neurotransmission

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