Decreased Serum Glutamate Levels in Male Adults with Internet Gaming Disorder: A Pilot Study.

OBJECTIVE: Alteration in glutamatergic neurotransmission and dopaminergic dysfunction has been implicated in both the initiation and expression of addiction related behaviors. This pilot study was aimed to investigate the serum levels of glutamate and dopamine in adults with internet gaming disorder (IGD). METHODS: We measured serum levels of glutamate and dopamine in male participants with IGD (n=26) and age-matched healthy controls (n=25). Clinical interviews were performed to identify IGD and to rule out psychiatric comorbidities. Serum levels of glutamate and dopamine were examined by enzyme immunoassays using ELISA Kits. RESULTS: Serum levels of glutamate were lower among IGD than control (IGD: 24.184±12.303 µg/ml; control: 33.676±12.413 µg/ml; t=2.742, p=0.008), while levels of dopamine did not differ between. Serum glutamate and dopamine levels did not correlate with gaming hours and exposure to game in the IGD group. But serum glutamate levels were positively correlated with the dopamine levels (r=0.360, p=0.013). CONCLUSION: Our results suggest that altered glutamatergic neurotransmission may contribute to the pathophysiology of IGD.

Effects of acute and chronic methamphetamine administration on cynomolgus monkey hippocampus structure and cellular transcriptome.

Methamphetamine (MA), a psychostimulant abused worldwide, gives rise to neurotoxicity in the hippocampus, resulting in cognitive impairments and hippocampal volume reduction. The cellular and molecular mechanisms associated with hippocampal impairments due to MA remain unknown. The aim of this study was to investigate the effects of MA on structural alterations and gene expressions in the hippocampus. We analyzed the pattern of volumetric changes in the hippocampus using magnetic resonance imaging (MRI) after acute and chronic administration of MA to cynomolgus macaques. In addition, we performed large-scale transcriptome profiling in the hippocampus using RNA-Seq technology. The hippocampus in response to acute and chronic MA exhibited a significant volumetric atrophy compared with the hippocampus of controls. The genes associated with cytoskeleton organization and phagocytosis were downregulated in the acute MA-treated group compared to the control group. On the other hand, genes associated with synaptic transmission, regulation of neuron differentiation and regulation of neurogenesis were downregulated in the chronic MA-treated group. We confirmed that expression patterns for ADM, BMP4, CHRD, PDYN, UBA1, profilin 2 (PFN2), ENO2 and NSE mRNAs were similar to the results from RNA-Seq based on quantitative RT-PCR. In particular, PFN2 mRNA and protein expression levels, which play important roles in actin cytoskeleton dynamics, were decreased by acute and chronic MA administration. These results not only aid the understanding of cellular and molecular mechanisms regulated by MA in the hippocampus but also suggest basic information aiding biomarker and novel drug development for treating hippocampal impairment caused by MA abuse.

Prevalence Risk of Metabolic Syndrome Associated with Alcohol Use Behavior in Korean Women.

OBJECTIVE: Considerable research has been conducted on the relationship between alcohol consumption and metabolic syndrome. Although various standards for the amount and frequency of alcohol consumption have been suggested, a tool to measure individual alcohol use behavior against a consistent standard is required. Moreover, the association of alcohol use behavior with health should be examined on the basis of such a standard. In this study, we examined the relationships between alcohol use behavior according to the Alcohol Use Disorders Identification Test (AUDIT) and metabolic syndrome and its components in Korean women. METHODS: This study utilized data from the fifth Korean National Health and Nutrition Examination Survey, which was administered from 2010 through 2012. We investigated the relationships between alcohol use behavior and metabolic syndrome and its components in a sample of 2,906 women by using analysis of covariance and logistic regression analysis. RESULTS: After adjusting for confounding variables, alcohol use behavior was significantly associated with metabolic syndrome [odds ratio (OR) 2.877; 95% confidence interval (CI) 1.523-5.435 in the problem use group]. AUDIT score also was significantly related to abdominal obesity (OR 2.263; 95% CI 1.704-4.459 in the problem use group), hypertension (OR 3.377; 95% CI 1.871-6.095 in the problem use group), hypertriglyceridemia (OR 3.204; 95% CI 1.800-5.702 in the problem use group), and impaired fasting glucose (OR 3.034; 95% CI 1.721-5.348 in the problem use group). CONCLUSION: In this study, positive associations were observed between AUDIT score and risk of metabolic syndrome and its components.

The association between the nicotinic acetylcholine receptor α4 subunit gene (CHRNA4) rs1044396 and Internet gaming disorder in Korean male adults.

The primary aim of this study was to investigate the genetic predisposition of Internet gaming disorder (IGD), and the secondary aim was to compare the results to those of alcohol dependence (AD). Two independent case-control studies were conducted. A total of 30 male participants with IGD, diagnosed according to the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, and 30 sex-matched controls participated in study 1. We designed targeted exome sequencing (TES) to test for 72 candidate genes that have been implicated in the pathogenesis of addiction. The genes included seven neurotransmitter (dopamine, serotonin, glutamate, r-aminobutyric acid (GABA), norepinephrine, acetylcholine, and opioid) system genes. A total of 31 male in-patients with AD and 29 normal male controls (NC) were enrolled in study 2. The same 72 genes included in study 1 and ten additional genes related to alcohol-metabolic enzyme were selected as the target genes, and we identified the genetic variants using the same method (TES). The IGD group had a lower frequency of the T allele of rs1044396 in the nicotinic acetylcholine receptor alpha 4 subunit (CHRNA4), and this variant represents a protective allele against IGD. However, we did not find a significant difference in the polymorphisms of the 72 genes that encode neurotransmitter systems between the AD and NC groups. This study demonstrated that rs1044396 of CHRNA4 was significantly associated with IGD.

An association study of Taq1A ANKK1 and C957T and - 141C DRD2 polymorphisms in adults with internet gaming disorder: a pilot study.

BACKGROUND: Though Internet gaming disorder (IGD) is considered to share similar genetic vulnerability with substance addictions, little has been explored about the role of the genetic variants on IGD. This pilot study was designed to investigate the association of the Taq1A polymorphism of the ankyrin repeat and kinase domain containing 1 (ANKK1) gene and C957T and - 141C of the dopamine D2 receptor (DRD2) with IGD and their role on the personality and temperament traits in IGD among adult population. METHODS: Sixty-three subjects with IGD and 87 control subjects who regularly played Internet games were recruited. Self-administered questionnaires on self-control, dysfunctional impulsivity, and temperament and character domains were done. The Taq1A ANKK1 and the C957T and - 141C ins/del from the DRD2 genes were genotyped using the specific TaqMan PCR assay. RESULTS: The distributions of allele and genotype frequencies were not significantly different between the IGD and control groups in both genders. In male, excessive gaming and use of gaming to escape from a negative feeling were associated with the del- genotype of the - 141C. Among IGD, the del+ genotype was associated with higher novelty seeking. Logistic regression showed no predictive value of these polymorphisms for IGD when using age and gender as covariates. CONCLUSIONS: Though no direct association of the Taq1A ANKK1 and C957T DRD2 variants with IGD were observed, the - 141C polymorphism may play a role in IGD via mediating symptoms or temperament traits.

Chronic saponin treatment attenuates damage to the pancreas in chronic alcohol-treated diabetic rats.

BACKGROUND: Chronic heavy alcohol consumption may raise the risk of developing type 2 diabetes mellitus. Saponins inhibit apoptosis of pancreatic islet cells and reduce lipid parameters. The present study was designed to investigate the effect of saponin on chronic ethanol-treated diabetic rats. METHODS: Long-Evans Tokushima Fatty (LETO) and Otsuka Long-Evans Tokushima Fatty (OLETF) rats were pair-fed a Lieber-DeCarli diet with and without 5% ethanol for 12 wks. Two weeks after starting the pair-feeding with the Lieber-DeCarli diet, intraperitoneal injection of saponin was performed for 10 wks. To perform the experiments, rats were divided as follows: LETO-Control (LC), LETO-Ethanol (LE), LETO-Ethanol-Saponin (LES), OLETF-Control (OC), OLETF-Ethanol (OE), and OLETF-Ethanol-Saponin (OES). RESULTS: The weights of epididymal and mesenteric fat tissue in LES and OES rats were the lightest from among the LETO and OLETF groups, respectively. The secretion of alanine aminotransferase and cholesterol in OES rats decreased significantly compared to their secretion in OC and OE rats, respectively. The islets of the pancreas in LE and OE rats showed clean, unclear, and smaller morphology compared to those of LC, LES, OC, and OES rats. In addition, the expression of insulin in the islets of the pancreas in LC, LES, OC, and OES rats was higher than in LE and OE rats. CONCLUSION: Saponin may not only be helpful in alleviating the rapid progress of diabetes due to chronic alcohol consumption in diabetic patients, but may also show potential as an antidiabetic drug candidate for diabetic patients who chronically consume alcohol.

Association Between Drinking and Obesity in Pre- and Postmenopausal Women: Korea National Health and Nutrition Examination Survey 2010-2012.

BACKGROUND: Women are more vulnerable to the adverse effects of alcohol than men. The present study aimed to investigate the link between drinking and obesity in pre- and postmenopausal women in Korea. METHODS: We performed a cross-sectional study of 4374 premenopausal and 2927 postmenopausal women using a multistage probability cluster survey sample to produce nationally representative estimates. We assessed the subjects' alcohol drinking tendencies rates according to their drinking levels as well as Alcohol Use Disorders Identification Test (AUDIT); obesity was identified based on body mass index (BMI) ≥25 kg/m2, waist circumference (WC) ≥80 cm, and waist-to-height ratio (WHtR) ≥50%. We performed t-tests and chi-square tests to assess the association between drinking and obesity. RESULTS: In premenopausal subjects, obesity indices increased significantly as alcohol consumption rose. Significant correlations between drinking level and obesity factors were found in premenopausal women after adjusting for age (odds ratios [ORs] for BMI, WC, and WHtR were 1.58 [1.08-2.31], 1.94 [1.11-3.00], and 1.80 [1.24-2.61], respectively). Furthermore, an AUDIT score of 20 or higher indicated a significantly higher likelihood of obesity (ORs for BMI, WC, and WHtR were 2.02 [1.18-3.46], 2.75 [1.70-4.87], and 2.86 [1.78-4.59], respectively). There was a significant correlation between AUDIT scores and obesity factors after adjusting for age, energy intake, fat intake, exercise, smoking, education, and income in premenopausal women (ORs for BMI and WHtR were 1.71 [0.85-3.47] and 1.73 [0.97-3.06], respectively). CONCLUSION: Our results suggest that alcohol is associated with a risk factor for obesity in premenopausal women.