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.