scholarly journals The glucagon-like peptide-1 receptor as a potential treatment target in alcohol use disorder: evidence from human genetic association studies and a mouse model of alcohol dependence

2015 ◽  
Vol 5 (6) ◽  
pp. e583-e583 ◽  
Author(s):  
P Suchankova ◽  
J Yan ◽  
M L Schwandt ◽  
B L Stangl ◽  
E C Caparelli ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Mouse Model ◽  
Alcohol Dependence ◽  
Alcohol Use Disorder ◽  
Association Studies ◽  
Genetic Association Studies ◽  
Potential Treatment ◽  
Treatment Target ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals A Genetically Modified Skin Graft for Treating Alcohol Use Disorder and/or Polysubstance Abuse With Cocaine

2021 ◽  
Vol 11 ◽  
Author(s):  
Qingyao Kong ◽  
Xiaoyang Wu ◽  
Ming Xu
Keyword(s):  
Alcohol Use ◽  
Gene Delivery ◽  
Alcohol Use Disorder ◽  
Genetically Modified ◽  
Unmet Need ◽  
Delivery Platform ◽  
Polysubstance Abuse ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Grafting Procedure

Alcohol use disorder (AUD) is one of the foremost public health problems. Alcohol is also frequently co-abused with cocaine. There is a huge unmet need for the treatment of AUD and/or cocaine co-abuse. We have developed and used a skin stem cell-based gene delivery platform and found that production of the glucagon-like peptide-1 (GLP1) from the grafted genetically modified skin reduced development and reinstatement of alcohol-induced drug-taking and seeking, voluntary oral alcohol consumption and alcohol-induced increase in dopamine (DA) levels in the nucleus accumbens (NAc). Moreover, we have developed a novel co-grafting procedure for both modified human butyrylcholinesterase (hBChE)- and GLP1-expressing cells. Skin grafts-derived hBChE and GLP1 reduced acquisition of drug-taking and toxicity induced by concurrent alcohol and cocaine injections. These results imply that gene delivery through skin transplants may add a new option to treat drug abuse and co-abuse.

scholarly journals Neuroendocrine Response to Exogenous Ghrelin Administration, Combined With Alcohol, in Heavy-Drinking Individuals: Findings From a Randomized, Double-Blind, Placebo-Controlled Human Laboratory Study

2021 ◽  
Author(s):  
Mehdi Farokhnia ◽  
Kelly M Abshire ◽  
Aaron Hammer ◽  
Sara L Deschaine ◽  
Anitha Saravanakumar ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Heavy Drinking ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Alcohol Administration ◽  
Neuroendocrine Response ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Human Laboratory

Abstract Background Accumulating evidence has established a role for the orexigenic hormone ghrelin in alcohol-seeking behaviors. Accordingly, the ghrelin system may represent a potential pharmacotherapeutic target for alcohol use disorder. Ghrelin modulates several neuroendocrine pathways, such as appetitive, metabolic, and stress-related hormones, which are particularly relevant in the context of alcohol use. The goal of the present study was to provide a comprehensive assessment of neuroendocrine response to exogenous ghrelin administration, combined with alcohol, in heavy-drinking individuals. Methods This was a randomized, crossover, double-blind, placebo-controlled human laboratory study, which included 2 experimental alcohol administration paradigms: i.v. alcohol self-administration and i.v. alcohol clamp. Each paradigm consisted of 2 counterbalanced sessions of i.v. ghrelin or placebo administration. Repeated blood samples were collected during each session, and peripheral concentrations of the following hormones were measured: leptin, glucagon-like peptide-1, pancreatic polypeptide, gastric inhibitory peptide, insulin, insulin-like growth factor-1, cortisol, prolactin, and aldosterone. Results Despite some statistical differences, findings were consistent across the 2 alcohol administration paradigms: i.v. ghrelin, compared to placebo, increased blood concentrations of glucagon-like peptide-1, pancreatic polypeptide, cortisol, and prolactin, both acutely and during the whole session. Lower levels of leptin and higher levels of aldosterone were also found during the ghrelin vs placebo session. Conclusion These findings, gathered from a clinically relevant sample of heavy-drinking individuals with alcohol use disorder, provide a deeper insight into the complex interplay between ghrelin and appetitive, metabolic, and stress-related neuroendocrine pathways in the context of alcohol use.

Co-Purification of Recombinant Modified Glucagon-Like and Glucose-Dependent Insulinotropic Peptide to Create a Two-Component Drug for the Treatment of Type 2 Diabetes Mellitus and Obesity

2021 ◽  
Vol 37 (6) ◽  
pp. 74-83
Author(s):  
A.Yu. Gorbunova ◽  
E.P. Sannikova ◽  
I.I. Gubaidullin ◽  
O.M. Ignatova ◽  
M.Yu. Kopaeva ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Mouse Model ◽  
Specific Activity ◽  
Two Component ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Insulinotropic Peptide

In addition to the previously developed recombinant modified human glucagon-like peptide 1 (rmglp1, Glypin), a recombinant modified human glucose-dependent insulinotropic peptide (RMGIP) has been obtained. A new universal reverse-phase HPLC technique has been proposed allowing quantitative analysis of rmGlp1 and rmGip separately and as part of a two-component preparation. The data show that the design of recombinant human rmGip according to the Glypine formula makes it possible to produce one-component and two-component preparations containing various rmGip and rmGlp1 protein ratios ranging from 1:0 to 20:1, using cell biomass samples mixed in predetermined proportions. Studies of human rmGip activity in a mouse model revealed reduced specific activity and signs of weak antagonistic effects. In this regard, there is a need for further study of human rmGip activity in a mouse model, including the use of alternative mouse or rat rmGip. type 2 diabetes mellitus; two-component drug, glucose-dependent insulinotropic peptide, glucagon-like peptide-1 The work was supported by the Internal Grant from National Research Center Kurchatov Institute.

scholarly journals Evaluation of childhood traumatic experience as a risk factor for alcohol use disorder in adulthood

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Lan Wang ◽  
Cui-Xia An ◽  
Mei Song ◽  
Na Li ◽  
Yuan-Yuan Gao ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alcohol Use ◽  
Alcohol Abuse ◽  
Alcohol Dependence ◽  
Physical Abuse ◽  
Emotional Abuse ◽  
Alcohol Use Disorder ◽  
Alcohol Use Disorders ◽  
Traumatic Experience ◽  
Frequent Drinking

Abstract Background We aimed to investigate the effect of early-age (prenatal, infant, and childhood) trauma on adulthood alcohol use disorder. Methods A total number of 1534 subjects who were born and live in the city of Tangshan were selected. The subjects were divided into three age groups. General demographic data, conditions of the mothers during pregnancy, and condition of the babies at birth, were collected. The diagnosis of alcohol use disorder was based on Structured Clinical Interviews for DSM-IV Axis Disorders (patient version) (SCID). The childhood trauma questionnaire short form (CTQ-SF) [1] and the Lifetime of Experience Questionnaire (LTE-Q) [2] were used to evaluate stress in childhood and adulthood, respectively. Results Only male subjects were diagnosed with lifelong alcohol abuse and alcohol dependence. There was no statistically significant difference in the prevalence of lifetime alcohol use disorder (X2 = 4.480, P = 0.345), current alcohol abuse, and current alcohol dependence among the three groups (X2abuse = 2.177, X2depedence = 2.198, P > 0.05). However, higher prevalence of lifetime alcohol use disorders was found in group with higher scores of CTQ (X2 = 9.315, P = 0.009), emotional abuse (X2 = 8.025, P = 0.018), physical abuse (X2 = 20.4080, P < 0.001), but not in the group with higher scores of emotional neglect (X2 = 1.226, P = 0.542), sexual abuse (X2 = 2.779, P = 0.249), physical neglect (X2 = 3.978, P = 0.137), LTE-Q (X2 = 5.415, P = 0.067), and PSQI (X2 = 5.238, P = 0.073). Protective factor for alcohol abuse for men was identified to be heavy drinking (OR = 0.085, 95%CI: 0.011–0.661), and the risk factors for alcohol abuse were identified to be frequent drinking (OR = 2.736, 95%CI: 1.500, 4.988), and consumption of low liquor (OR = 2.563, 95%CI: 1.387, 4.734). Risk factors for alcohol dependence in males were identified to be consumption of low liquor (OR = 5.501, 95%CI: 2.004, 15.103), frequent drinking (OR = 2.680, 95%CI: 1.164, 6.170), and childhood physical abuse (OR = 2.310, 95% CI: 1.026, 5.201). Conclusion Traumatic experience during infant and prenatal periods does not have a strong statistical correlation with alcohol use disorders for male adults. However, subjects with high CTQ scores, experience of emotional abuse and physical abuse show a statistically higher prevalence of lifetime alcohol use disorders. Several risk factors including consumption of low liquor, frequent drinking, and childhood physical abuse contribute to alcohol dependence in male adults.

scholarly journals Educational attainment impacts drinking behaviors and risk for alcohol dependence: results from a two-sample Mendelian randomization study with ~780,000 participants

2019 ◽  
Author(s):  
Daniel B. Rosoff ◽  
Toni-Kim Clarke ◽  
Mark J. Adams ◽  
Andrew M. McIntosh ◽  
George Davey Smith ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Educational Attainment ◽  
Alcohol Dependence ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Significant Snps ◽  
Genome Wide Association Studies ◽  
Reverse Causality ◽  
Genome Wide ◽  
Genetic Instruments

Abstract Observational studies suggest that lower educational attainment (EA) may be associated with risky alcohol use behaviors; however, these findings may be biased by confounding and reverse causality. We performed two-sample Mendelian randomization (MR) using summary statistics from recent genome-wide association studies (GWAS) with >780,000 participants to assess the causal effects of EA on alcohol use behaviors and alcohol dependence (AD). Fifty-three independent genome-wide significant SNPs previously associated with EA were tested for association with alcohol use behaviors. We show that while genetic instruments associated with increased EA are not associated with total amount of weekly drinks, they are associated with reduced frequency of binge drinking ≥6 drinks (ßIVW = −0.198, 95% CI, −0.297 to –0.099, PIVW = 9.14 × 10−5), reduced total drinks consumed per drinking day (ßIVW = −0.207, 95% CI, −0.293 to –0.120, PIVW = 2.87 × 10−6), as well as lower weekly distilled spirits intake (ßIVW = −0.148, 95% CI, −0.188 to –0.107, PIVW = 6.24 × 10−13). Conversely, genetic instruments for increased EA were associated with increased alcohol intake frequency (ßIVW = 0.331, 95% CI, 0.267–0.396, PIVW = 4.62 × 10−24), and increased weekly white wine (ßIVW = 0.199, 95% CI, 0.159–0.238, PIVW = 7.96 × 10−23) and red wine intake (ßIVW = 0.204, 95% CI, 0.161–0.248, PIVW = 6.67 × 10−20). Genetic instruments associated with increased EA reduced AD risk: an additional 3.61 years schooling reduced the risk by ~50% (ORIVW = 0.508, 95% CI, 0.315–0.819, PIVW = 5.52 × 10−3). Consistency of results across complementary MR methods accommodating different assumptions about genetic pleiotropy strengthened causal inference. Our findings suggest EA may have important effects on alcohol consumption patterns and may provide potential mechanisms explaining reported associations between EA and adverse health outcomes.

scholarly journals Alcohol craving and the dimensionality of alcohol disorders

2010 ◽  
Vol 41 (3) ◽  
pp. 629-640 ◽  
Author(s):  
K. M. Keyes ◽  
R. F. Krueger ◽  
B. F. Grant ◽  
D. S. Hasin
Keyword(s):  
Alcohol Use ◽  
Alcohol Dependence ◽  
Latent Variable ◽  
Alcohol Use Disorder ◽  
Alcohol Problems ◽  
Continuous Measure ◽  
Alcohol Disorders ◽  
Alcohol Craving ◽  
Epidemiologic Survey ◽  
Dsm Iv

BackgroundICD-10 includes a craving criterion for alcohol dependence while DSM-IV does not. Little is known about whether craving fits with or improves the DSM-IV criteria set for alcohol-use disorders.MethodData were derived from current drinkers (n=18 352) in the 1991–1992 National Longitudinal Alcohol Epidemiologic Survey (NLAES), a nationally representative survey of US adults >17 years of age. The Alcohol Use Disorder and Associated Disabilities Interview Schedule was used to assess the eleven DSM-IV dependence and abuse criteria, and alcohol craving. Exploratory factor, item response theory, and regression analyses were used to evaluate the psychometric properties and concurrent validity of DSM-based alcohol disorder criteria with the addition of alcohol craving.ResultsThe past 12-month prevalence of craving was 1.3%. Craving formed part of a unidimensional latent variable that included existing DSM-IV criteria. Craving demonstrated high severity on the alcohol-use disorder continuum, resulting in an improved dimensional model with greater discriminatory ability compared with current DSM-IV criteria. Correlates of the diagnosis did not change with the addition of craving, and past 12-month craving was associated with prior alcohol dependence, depression, and earlier age of alcohol disorder onset among those with current DSM-IV alcohol dependence.ConclusionsThe addition of craving to the existing DSM-IV criteria yields a continuous measure that better differentiates individuals with and without alcohol problems along the alcohol-use disorder continuum. Few individuals are newly diagnosed with alcohol dependence given the addition of craving, indicating construct validity but redundancy with existing criteria.

Connections between personality and the symptomatology of alcohol use disorder

2011 ◽  
Vol 26 (S2) ◽  
pp. 71-71
Author(s):  
E. Kurgyis ◽  
B. Andó ◽  
S. Rózsa ◽  
A. Szkaliczki ◽  
I. Demeter ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Alcohol Dependence ◽  
Symptom Severity ◽  
Impulse Control ◽  
Alcohol Use Disorder ◽  
Specific Impulse ◽  
Personality Factors ◽  
Clinical Aspects ◽  
Novelty Seeking ◽  
Dsm Iv

IntroductionTemperament and character factors and specific impulse control-related personality traits are connected to the developmental and clinical aspects of alcohol use disorder (AUD).Objectives/aimsTo reveal the underlying personality structure of individual differences in the symptom severity of AUD. Therefore temperament and character, impulsivity and aggression were assessed in relation to alcohol addiction severity.MethodsSixty-three patients with AUD were involved. Temperament and Character Inventory-Revised was used to quantify temperament and character dimensions. Impulsivity was assessed by the Barratt Impulsivity Scale-11 (BIS) and aggression by the Buss-Perry Aggression Questionnaire (BPAQ). To determine symptom severity of AUD the Severity of Alcohol Dependence Questionnaire (SADQ), the Alcohol Use Disorders Identification Test (AUDIT), the MacAndrew Alcoholism Scale-Revised (MAC-R) and the number of DSM-IV alcohol dependence symptoms were registered. To analyze the connections between symptom severity indicators and personality factors Pearson and Spearman correlation analysis were applied, p < 0.05 were considered significant.ResultsSADQ (r = 0.290), AUDIT (r = 0.345), MAC-R (r = 0.504) and the DSM-IV alcohol dependence symptoms (Spearman rho = 0.271) correlated positively with novelty-seeking temperament factor. SADQ (r = 0.262) and AUDIT (r = 0.293) scores correlated positively with BIS. Furthermore SADQ (r = 0.382), AUDIT (r = 0.318), MAC-R (r = 0.416) correlated positively with BPAQ.ConclusionsNovelty-seeking, impulsivity and aggression as indicators of impulse control have different theoretical backgrounds but a common root. This study has revealed that the adverse consequences of lower impulse control can lead to more severe symptoms of AUD. These connections between impulse control and the symptomatology could contribute to a better understanding of the clinical complexity of AUD.

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