Addiction Rehab: Exploratory Study on Association of Genetic Variation in TBC1D1 With Antipsychotic-Induced Weight Gain.

Exploratory study on association of genetic variation in TBC1D1 with antipsychotic-induced weight gain.

Filed under: Addiction Rehab

Hum Psychopharmacol. 2013 Jan 30;
Brandl EJ, Tiwari AK, Lett TA, Shaikh SA, Lieberman JA, Meltzer HY, Kennedy JL, Müller DJ

BACKGROUND: Previous studies have shown that antipsychotics with high propensity for antipsychotic-induced weight gain (AIWG) influence glucose transporter type 4 (GLUT4) mediated glucose intake. Variation in the gene encoding TBC1 domain family member 1 (TBC1D1), a Rab-GTPase activating protein regulating GLUT4 trafficking, has been associated with obesity. Therefore, we investigated the impact of TBC1D1 polymorphisms on AIWG. METHODS: We analyzed rs9852 and rs35859249 in TBC1D1 in 195 schizophrenia subjects treated mostly with clozapine or olanzapine for up to 14?weeks. Association was tested using analysis of variance and analysis of covariance with change (%) from baseline weight as the dependent variable. RESULTS: Analysis of covariance showed a non-significant trend for lower weight gain in carriers of the T-allele of rs9852 than in C-allele homozygotes (p?=?0.063). This effect was more pronounced in the subgroup of patients treated with clozapine or olanzapine (p?=?0.024). For rs35859249, no significant association with AIWG could be detected. CONCLUSIONS: This is the first study examining the association between TBC1D1 and AIWG. The moderate association of rs9852, located in the 3’UTR near a miRNA binding site, indicates an influence of TBC1D1 on AIWG. Further investigations remain necessary to elucidate the role of this gene in AIWG. Copyright © 2013 John Wiley & Sons, Ltd.
HubMed – addiction


Combination treatment of epilepsy with ketogenic diet and concurrent pharmacological inhibition of cytochrome P450 2E1.

Filed under: Addiction Rehab

Med Hypotheses. 2013 Jan 28;
Palmer M

While most epileptic patients respond to treatment with existing antiepileptic drugs, there remains a considerable number of patients in whom these drugs do not suffice. Such patients, particularly children, are often treated using the ketogenic diet. This diet imposes a strict limit on carbohydrates; while providing for adequate protein, most of the calories are supplied as triacylglycerol, much of which is metabolized to ketone bodies. Animal experiments have provided evidence that the anticonvulsant effect of the ketogenic diet is mediated by acetone and correlates with blood acetone levels. Acetone can be converted in vivo to glucose via acetol and pyruvate; the initial conversion to acetol is catalyzed by cytochrome P450 2E1 (CYP2E1). When CYP2E1 knockout mice are subjected to starvation to induce ketogenesis, they develop blood acetone levels much higher than those observed in wild-type mice. Similarly, pharmacological inhibition of CYP2E1 significantly increases blood acetone levels in rat and man. Taken together, these observations suggest that pharmacological inhibition of CYP2E1 has the potential to significantly increase the antiepileptic effect of the ketogenic diet. With patients that respond insufficiently to the diet alone, increased acetone levels may improve response. With patients who respond sufficiently to the diet, CYP2E1 inhibitors might allow a relaxation of the fairly severe diet regimen and so improve compliance and quality of life. An existing inhibitor of CYP2E1 is the drug disulfiram. This drug also inhibits the enzyme aldehyde dehydrogenase, which functions in alcohol degradation, and in this capacity has long been used in the treatment of alcohol addiction. Disulfiram inhibits CYP2E1 at conventional therapeutic dosages and increases blood acetone levels in humans and animals. It should therefore be a viable candidate for the proposed drug/diet combination treatment.
HubMed – addiction


Relationship of Internet Addiction Severity with Depression, Anxiety, and Alexithymia, Temperament and Character in University Students.

Filed under: Addiction Rehab

Cyberpsychol Behav Soc Netw. 2013 Jan 30;
Dalbudak E, Evren C, Aldemir S, Coskun KS, Ugurlu H, Yildirim FG

Abstract The aim of the study was to investigate the relationship of Internet addiction (IA) severity with alexithymia, temperament, and character dimensions of personality in university students while controlling for the effect of depression and anxiety. A total of 319 university students from two conservative universities in Ankara volunteered for the study. Students were investigated using the Toronto Alexithymia Scale-20, the Temperament and Character Inventory, the Internet Addiction Scale, the Beck Anxiety Inventory, and the Beck Depression Inventory. Of the university students enrolled in the study, 12.2 percent (n=39) were categorized into the moderate/high IA group (IA 7.2 percent, high risk 5.0 percent), 25.7 percent (n=82) were categorized into the mild IA group, and 62.1 percent (n=198) were categorized into the group without IA. Results revealed that the rate of moderate/high IA group membership was higher in men (20.0 percent) than women (9.4 percent). Alexithymia, depression, anxiety, and novelty seeking (NS) scores were higher; whereas self-directedness (SD) and cooperativeness (C) scores were lower in the moderate/high IA group. The severity of IA was positively correlated with alexithymia, whereas it was negatively correlated with SD. The “difficulty in identifying feelings” and “difficulty in describing feelings” factors of alexithymia, the low C and high NS dimensions of personality were associated with the severity of IA. The direction of this relationship between alexithymia and IA, and the factors that may mediate this relationship are unclear. Nevertheless, university students exhibiting high alexithymia and NS scores, along with low character scores (SD and C) should be closely monitored for IA.
HubMed – addiction


Using genetic information from candidate gene and genome-wide association studies in risk prediction for alcohol dependence.

Filed under: Addiction Rehab

Addict Biol. 2013 Jan 30;
Yan J, Aliev F, Webb BT, Kendler KS, Williamson VS, Edenberg HJ, Agrawal A, Kos MZ, Almasy L, Nurnberger JI, Schuckit MA, Kramer JR, Rice JP, Kuperman S, Goate AM, Tischfield JA, Porjesz B, Dick DM

Family-based and genome-wide association studies (GWAS) of alcohol dependence (AD) have reported numerous associated variants. The clinical validity of these variants for predicting AD compared with family history information has not been reported. Using the Collaborative Study on the Genetics of Alcoholism (COGA) and the Study of Addiction: Genes and Environment (SAGE) GWAS samples, we examined the aggregate impact of multiple single nucleotide polymorphisms (SNPs) on risk prediction. We created genetic sum scores by adding risk alleles associated in discovery samples, and then tested the scores for their ability to discriminate between cases and controls in validation samples. Genetic sum scores were assessed separately for SNPs associated with AD in candidate gene studies and SNPs from GWAS analyses that met varying P-value thresholds. Candidate gene sum scores did not exhibit significant predictive accuracy. Family history was a better classifier of case-control status, with a significant area under the receiver operating characteristic curve (AUC) of 0.686 in COGA and 0.614 in SAGE. SNPs that met less stringent P-value thresholds of 0.01-0.50 in GWAS analyses yielded significant AUC estimates, ranging from mean estimates of 0.549 for SNPs with P?HubMed – addiction



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