| 1. |
- Adermark, Louise, 1974, et al.
(author)
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Disentangling the Role of Astrocytes in Alcohol Use Disorder
- 2016
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In: Alcoholism-Clinical and Experimental Research. - : Wiley. - 0145-6008. ; 40:9
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Journal article (peer-reviewed)abstract
- Several laboratories recently identified that astrocytes are critical regulators of addiction machinery. It is now known that astrocyte pathology is a common feature of ethanol (EtOH) exposure in both humans and animal models, as even brief EtOH exposure is sufficient to elicit long-lasting perturbations in astrocyte gene expression, activity, and proliferation. Astrocytes were also recently shown to modulate the motivational properties of EtOH and other strongly reinforcing stimuli. Given the role of astrocytes in regulating glutamate homeostasis, a crucial component of alcohol use disorder (AUD), astrocytes might be an important target for the development of next-generation alcoholism treatments. This review will outline some of the more prominent features displayed by astrocytes, how these properties are influenced by acute and long-term EtOH exposure, and future directions that may help to disentangle astrocytic from neuronal functions in the etiology of AUD.
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| 2. |
- Ahlner, Felicia, 1987, et al.
(author)
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Increased Alcohol Consumption Among Swedish 70-Year-Olds 1976 to 2016: Analysis of Data from The Gothenburg H70 Birth Cohort Studies, Sweden
- 2018
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In: Alcoholism: Clinical and Experimental Research. - : Wiley. - 0145-6008. ; 42:12, s. 2403-2412
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Journal article (peer-reviewed)abstract
- © 2018 by the Research Society on Alcoholism Background: The older adult population is increasing worldwide, as is the number of older adults who consume alcohol. Although there is a growing body of research on alcohol consumption among older people, few studies focus on changes in at-risk consumption over time across well-defined birth cohorts of older adults. Methods: This study used a serial cross-sectional design in order to compare alcohol consumption patterns among birth cohorts of Swedish 70-year-olds (total n=2,268) examined in 1976 to 1977 (n=393), 1992 to 1993 (n=248), 2000 to 2002 (n=458), and 2014 to 2016 (n=1,169). Participants took part in a multidisciplinary study on health and aging. Face-to-face interviews were conducted by healthcare professionals. Protocols regarding alcohol consumption were similar for all cohorts. The volume of weekly alcohol consumption was estimated during the past month. At-risk consumption was defined as ≥100g alcohol/wk corresponding roughly to the National Institute on Alcohol Abuse and Alcoholism definition of heavy consumption. Results: The proportion of at-risk consumers among men increased from 16.1% in 1976 to 1977 to 29.9% in 2000 to 2002 (p=0.001) and 45.3% in 2014 to 2016 (p<0.001). In women, proportions were low in 1976 to 1977 (0.5%) and 1992 to 1993 (2.0%; p=0.134), but increased to 9.5% in 2000 to 2002 (p<0.001) and 24.3% in 2014 to 2016 (p<0.001). The male:female ratio regarding consumption of ≥100g/wk decreased from 32.2:1 in 1976 to 1977 to 3.1:1 in 2000 to 2002 to 1.9:1 in 2014 to 2016. Spirit consumption decreased dramatically among men during the study period, while women reported very low spirit consumption at all examinations. Wine consumption increased in both sexes between 2000 to 2002 and 2014 to 2016. Beer consumption increased among men between 2000 to 2002 and 2014 to 2016. Conclusions: Recent cohorts of 70-year-olds in Sweden report significantly higher levels of alcohol consumption than previous cohorts. There was a dramatic increase in at-risk consumption among 70-year-olds from the 1970s to the mid-2010s, and this was particularly pronounced among women.
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| 3. |
- Baker, Jessica H., et al.
(author)
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Associations Between Alcohol Involvement and Drive for Thinness and Body Dissatisfaction in Adolescent Twins : A Bivariate Twin Study
- 2018
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In: Alcoholism. - : Wiley-Blackwell. - 0145-6008 .- 1530-0277. ; 42:11, s. 2214-2223
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Journal article (peer-reviewed)abstract
- BACKGROUND: Alcohol involvement has familial associations with bulimic symptoms (i.e., binge eating, inappropriate compensatory behaviors), with several studies indicating a genetic overlap between the two. It is unclear whether overlapping familial risk with alcohol involvement extends to other eating disorder symptoms. Understanding the genetic overlap between alcohol involvement and other eating disorder symptoms may aid in more targeted interventions for comorbid alcohol use-eating disorder symptoms. Thus, we investigated associations between alcohol involvement and 2 core eating disorder symptoms: drive for thinness and body dissatisfaction in adolescent female and male twins.METHODS: We assessed 3 levels of alcohol involvement: alcohol use in the last month, having ever been intoxicated, and alcohol intoxication frequency via self-report. The Eating Disorder Inventory-II assessed drive for thinness and body dissatisfaction. Sex-specific biometrical twin modeling examined the genetic overlap between alcohol involvement and eating disorder symptoms.RESULTS: Phenotypic associations between alcohol involvement, drive for thinness, and body dissatisfaction were significantly greater in girls compared with boys. A majority of the associations between alcohol involvement, drive for thinness, and body dissatisfaction in girls, but not boys, met our threshold for twin modeling (phenotypic r > 0.20). Moderate genetic correlations were observed between the 3 aspects of alcohol involvement and drive for thinness. Moderate genetic correlations were observed between alcohol use and intoxication frequency and body dissatisfaction.CONCLUSIONS: Together with the literature on alcohol involvement and bulimic symptoms, these findings suggest a generalized association between alcohol involvement and eating disorder symptoms in girls, whereas this association may be symptom specific in boys. Genetic correlations indicate that the amount and direction of this genetic overlap differs across specific symptoms. When intervening on comorbid alcohol involvement and eating disorder symptoms, it may be important to target-specific eating disorder symptoms.
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| 4. |
- Bendre, Megha, et al.
(author)
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Associations Between MAOA-uVNTR Genotype, Maltreatment, MAOA Methylation, and Alcohol Consumption in Young Adult Males
- 2018
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In: Alcoholism. - : WILEY. - 0145-6008 .- 1530-0277. ; 42:3, s. 508-519
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Journal article (peer-reviewed)abstract
- BackgroundEpigenetic mechanisms are candidate moderators of the effect of maltreatment on brain and behavior. Interactions between maltreatment and the monoamine oxidase A upstream variable number tandem repeat genotype (MAOA-uVNTR) are associated with alcohol-related problems. However, presently it is not known whether DNA methylation moderates this association. The study focused on 53 young adult males and aimed to determine whether MAOA methylation moderated the association of alcohol-related problems with the interaction of MAOA-uVNTR and maltreatment, and whether alcohol consumption moderated the association of MAOA methylation with the interaction of MAOA-uVNTR and maltreatment. MethodsMAOA-uVNTR genotypes with 3 and > 3 repeats were categorized as short (S) and long (L), respectively. Data on maltreatment were obtained retrospectively, using self-reported questionnaires. DNA methylation of 16 candidate CpGs within part of the MAOA first exon and intron was assessed and grouped based on principal component analyses. Alcohol-related problems were assessed using the Alcohol Use Disorders Identification Test (AUDIT). Alcohol consumption was measured using AUDIT-C. Moderation effects were assessed and probed using the moderated moderation model and Johnson-Neyman's method, respectively. ResultsCarriers of the S allele, who experienced maltreatment and displayed lower Component 1 (mean of CpGs 13-16 in the first intron) MAOA methylation levels, reported higher AUDIT score in contrast to L-allele carriers. Carriers of the S allele, who reported higher AUDIT-C score and experienced maltreatment, displayed lower Component 3 (mean of CpGs 2-6 in the first exon) MAOA methylation levels than L-allele carriers. ConclusionsIntronic methylation moderated the association of alcohol-related problems with the interaction of MAOA-uVNTR and maltreatment. Alcohol consumption moderated the association of exonic methylation with the interaction of MAOA-uVNTR and maltreatment. These results suggest that epigenetic factors as well as genotype and maltreatment play a role in the development of alcohol misuse among young adult males.
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| 5. |
- Berglund, Kristina, 1969, et al.
(author)
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Is There a Need for Congruent Treatment Goals Between Alcohol-Dependent Patients and Caregivers?
- 2016
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In: Alcoholism-Clinical and Experimental Research. - : Wiley. - 0145-6008. ; 40:4, s. 874-879
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Journal article (peer-reviewed)abstract
- BackgroundAlcohol-dependent patients have different treatment goals when entering treatment. Furthermore, different treatment settings advocate different treatment goals. Earlier studies have pointed out that treatment goal is important for treatment outcome, both in the treatment setting as well as in the patients themselves. However, to our knowledge, no study has so far investigated the interaction between patient's goal and the goal of the treatment setting. The aim of the study was therefore to study the interaction between these 2 factors on treatment outcome. MethodsPatients' (n=201) goals from 2 treatment settingsone that had an abstinence-oriented goal and one with a low-risk drinking goalwere investigated. The patients were followed up 2.5years after treatment entry and effectiveness of congruent treatment goals on treatment outcome was investigated. ResultsThere was no significant association between congruent goals and treatment outcomes (p=0.060). However, when comparing the effectiveness of congruent treatment goal between the 2 treatment settings, the abstinence-oriented treatment setting was significantly more effective (p<0.01). ConclusionsThe major finding was that there appeared to be no association between congruence itself and treatment outcome. On the other hand, we found that the treatment outcome was more successful if the patient as well as the treatment setting had abstinence as a goal (i.e., congruent goals of abstinence).
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| 8. |
- Clarke, Rhona B. C., et al.
(author)
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Involvement of Inhibitory Receptors in Modulating Dopamine Signaling and Synaptic Activity Following Acute Ethanol Exposure in Striatal Subregions
- 2015
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In: Alcoholism-Clinical and Experimental Research. - : Wiley. - 0145-6008 .- 1530-0277. ; 39:12, s. 2364-2374
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Journal article (peer-reviewed)abstract
- Background: Alcohol acts on both inhibitory and excitatory receptor systems resulting in a net increase in dopamine output in the ventral striatum (nucleus accumbens [nAc]), which is implicated in drug reward. However, the dorsal striatum may also be involved in reward-related behaviors. The objectives of this study were to investigate the role of inhibitory receptors in modulating the acute effects of ethanol (EtOH) on dopamine release and synaptic activity in the shell region of the nAc (nAcS) and dorsolateral striatum (DLS). Methods: EtOH (300 mM) was administered via reversed microdialysis in the nAcS or DLS of Wistar rats following pretreatment with glycine or GABA(A) receptor antagonist strychnine and bicuculline, respectively. Dopamine content in dialysate samples was quantified using high-performance liquid chromatography. In addition, local field potential recordings were performed in the nAcS and DLS in slices from Wistar rats. Population spike (PS) amplitude was measured following treatment with EtOH (50 mM) in slices pretreated with strychnine or bicuculline. Results: Local EtOH increased dopamine levels in both regions, an effect that strychnine pretreatment inhibited in the nAcS. EtOH-induced increases in accumbal dopamine were not blocked by a low (5 mu M) concentration of bicuculline, but were inhibited by pretreatment with higher bicuculline concentrations. None of the antagonists administered in the DLS prevented the EtOH-induced dopamine increase. Field potential recordings in the nAcS showed that acute EtOH produced an increase in PS amplitude which was blocked by both strychnine and bicuculline. In the DLS, EtOH induced a decrease in PS amplitude which was not influenced by strychnine or bicuculline. Conclusions: The current results show that changes in striatal dopamine output and synaptic activity induced by acute EtOH administration are modulated by inhibitory receptors in a subregion-specific manner.
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| 9. |
- deBejczy, Andrea, et al.
(author)
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Varenicline for Treatment of Alcohol Dependence: A Randomized, Placebo-Controlled Trial
- 2015
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In: Alcoholism-Clinical and Experimental Research. - : Wiley. - 0145-6008 .- 1530-0277. ; 39:11, s. 2189-2199
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Journal article (peer-reviewed)abstract
- BackgroundAlcohol dependence is a devastating illness affecting a large population, and new pharmacological treatments with good efficacy are greatly needed. One potential candidate is varenicline, a smoking cessation agent with partial agonist action at (42) nicotinic acetylcholine receptors. MethodsA total of 160 subjects, 30 to 70years of age, fulfilling DSM-IV criteria for alcohol dependence without any serious physical or mental disorders, were recruited through advertisement at 3 university clinics in Sweden during March 2009 to January 2011. After a 2-week placebo run-in period, subjects received 2mg varenicline daily (titrated from 0.5mg during first week) or placebo for 12weeks in a double-blind manner. ResultsThe primary outcome was the proportion of heavy drinking days, measured by self-reported alcohol consumption. Primary and secondary outcomes were calculated as a mean over the 10-week steady-state active treatment period. In the primary outcome analysis, no effect of varenicline over placebo was found (p=0.73 for the intention to treat [ITT] and 0.92 for per protocol [PP]). Secondary outcome analysis found a significant reduction of specific alcohol marker phosphatidylethanol (PEth) in the blood in the varenicline group compared to placebo (p=0.02 ITT). Craving (p=0.048 PP) and Alcohol Use Disorders Identification Test (AUDIT) scores (p=0.015 ITT) were also reduced in the active treatment group. PEth more strongly correlated with self-reported alcohol consumption than carbohydrate-deficient ttransferrin and -glutamyl transferase, and correlation coefficients were higher in the varenicline group than in the placebo group for all markers. ConclusionsAlthough the results of the main outcome of this study did not support an effect of varenicline in alcohol-dependent individuals, the secondary analyses of PEth, craving and AUDIT score support an effect of varenicline on alcohol consumption. The disclosure of a treatment effect and the lack of a clear placebo effect when using PEth as outcome variable, together with a nonsymmetric bias associated with self-reported data, strongly argue for using the specific biomarker PEth in studies of treatments of alcohol dependence.
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