These data support polygenic contributions to methamphetamine dependence from genes that include those whose variants contribute to dependence on several addictive substances, success in quitting smoking, and mnemonic processes.

Susceptibility to drug dependence and drug-induced psychoses is influenced not only by the pharmacological effects of the drug but also by the genetic factors of the individual. To clarify the latter, we investigated the association between methamphetamine (METH) dependence/psychosis and the hDAT1 gene (SLC6A3) encoding the dopamine transporter, which is the primary site of METH activity in the brain. Four exonic polymorphisms of the hDAT1 gene, 242C/T (exon 2), 1342A/G (exon 9), 2319G/A (3 0 UTR), and VNTR (3 0 UTR) were examined. Although there was no significant difference in genotypic and allelic distribution of the four polymorphisms between all METH dependence/psychosis patients (N ¼ 124) and controls (N ¼ 160), the patients with METH psychosis lasting for 1 month or more after discontinuance of METH consumption showed a significant excess of nine-or fewer repeat alleles of the VNTR in 3 0 UTR of the hDAT1 gene (P ¼ 0.0054, OR ¼ 4.24, 95% CI ¼ 2. 46-7.31). The present study demonstrated that the presence of nineor fewer repeat alleles of hDAT1 is a strong risk factor for a worse prognosis of METH psychosis.

Acute exercise has been demonstrated to improve cognitive function. In contrast, severe hypoxia can impair cognitive function. Hence, cognitive function during exercise under severe hypoxia may be determined by the balance between the beneficial effects of exercise and the detrimental effects of severe hypoxia. However, the physiological factors that determine cognitive function during exercise under hypoxia remain unclear. Here, we examined the combined effects of acute exercise and severe hypoxia on cognitive function and identified physiological factors that determine cognitive function during exercise under severe hypoxia. The participants completed cognitive tasks at rest and during moderate exercise under either normoxic or severe hypoxic conditions. Peripheral oxygen saturation, cerebral oxygenation, and middle cerebral artery velocity were continuously monitored. Cerebral oxygen delivery was calculated as the product of estimated arterial oxygen content and cerebral blood flow. On average, cognitive performance improved during exercise under both normoxia and hypoxia, without sacrificing accuracy. However, under hypoxia, cognitive improvements were attenuated for individuals exhibiting a greater decrease in peripheral oxygen saturation. Cognitive performance was not associated with other physiological parameters. Taken together, the present results suggest that arterial desaturation attenuates cognitive improvements during exercise under hypoxia.

No abstract

Human dopamine transporter gene (DAT1) has a variable number of tandem repeats (VNTR) in its 3Ј-untranslated region (UTR).The association between the VNTR polymorphism and neuropsychiatric disorders has been studied, but their relationship is still unclear. Here we identified a novel polymorphism in the 3Ј-UTR of the DAT1 gene, G2319A, and a significant association between the polymorphism and alcoholism was observed in both genotypic and allelic frequencies (P = 0.040 and 0.019, extended Fisher's exact test, respectively). There was a significant gene dose effect on the risk for alcoholism associated with the 2319-A allele ( 2 = 6.16, df = 2, P = 0.046, linearity tendency test: Cochranq-Armitage analysis). Moreover, in the haplotype analysis with G2319A-and VNTR-polymorphisms, a positive gene dose efffect on the risk with the A10 allele (P = 0.044, linearity tendency test) and a negative gene dose effect with the G10 allele (P = 0.010, linearity tendency test) for alcoholism were significantly detected. Odds ratio for alcoholism with the A10 and G10 alleles were 1.76 (1.12-2.76) and 0.53 (0.32-0.79), respectively. These results indicate that the DAT1 gene may confer vulnerability to alcoholism.