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Association Analysis of Genetic Variants of the Serotonin and Dopamine System-regulated Genes in Methamphetamine Abusers

[ Vol. 4 , Issue. 3 ]

Author(s):

Jatuporn Namyen, Doungjai Buntup, Nanthawat Sitdhiraksa, Prapapun Chucharoen and Piyarat Govitrapong*   Pages 195 - 205 ( 11 )

Abstract:


Background: Methamphetamine (METH) dependence becomes the major public health concern for many countries. METH is an abusive stimulant with various psychophysiological effects to its abusers. METH activates the human's brain reward circuitry and addiction, by increasing dopamine (DA) and serotonin (5-HT) levels in the synaptic cleft.

Objective: We investigated allelic variants of 5-HTTLPR, 5-HT1A C(-1019)G, 5-HT2A (102 T/C), and DRD2 Taq IA gene polymorphisms.

Methods: Subjects were recruited and met the DSM-IV criteria of METH dependence. They were screened with Diagnostic Interview for Genetic Study (DIGS), Family Interview for Genetic Study (FIGS), and a short research questionnaire. Blood samples were collected, and DNA was extracted from leukocytes and PCR-amplified. The PCR products were then digested with enzymes: Hpy CH4IV, MspI, and Taq I restriction enzyme, respectively for 5-HT1A C(-1019)G, 5-HT2A (102 T/C), and DRD2 Taq IA. The genotypes were assigned on agarose gel size fractionation and allele identification.

Results: The results indicated that METH-dependent patients were likely to be poly-substance abusers. Genetic results showed that there were no differences between genetic variation of 5-HTTLPR, 5-HT1A C(-1019)G, and DRD2 Taq IA gene polymorphisms and METH dependence. For 5-HT2A 102T/C, T/C genotype was found to be significantly higher in METHdependent patients compared to healthy controls. Additionally, there was a significant difference for T allele of 5-HT2A 102T/C in METH-dependent patients with comorbidity of three prominent psychotic features: METH-induced psychosis, suicidal behaviors, and depressive symptoms.

Conclusion: These results suggest that the METH dependence, psychiatric comorbidity, and genetic variation can pose a challenge in the treatment of METH-dependent patients.

Keywords:

Methamphetamine, drug addiction, serotonin transporter, dopamine transporter, serotonin receptor, dopamine receptor, genetic variation.

Affiliation:

Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom 73170, Addiction Studies Program, ASEAN Institute for Health Development, Mahidol University, Nakhon Pathom 73170, Department of Psychiatry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Addiction Studies Program, ASEAN Institute for Health Development, Mahidol University, Nakhon Pathom 73170, Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom 73170

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