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1.  Transitions In and Out of Alcohol Use Disorders: Their Associations with Conditional Changes in Quality of Life Over a 3-Year Follow-Up Interval† 
Aims: The aim of this study was to investigate longitudinal changes in quality of life (QOL) as a function of transitions in alcohol use disorders (AUD) over a 3-year follow-up of a general US population sample. Methods: The analysis is based on individuals who drank alcohol in the year preceding the Wave 1 National Epidemiologic Survey on Alcohol and Related Conditions and were reinterviewed at Wave 2 (n = 22,245). Using multiple linear regression models, changes in SF-12 QOL were estimated as a function of DSM-IV AUD transitions, controlling for baseline QOL and multiple potential confounders. Results: Onset and offset of AUD were strongly associated with changes in mental/psychological functioning, with significant decreases in mental component summary (NBMCS) scores among individuals who developed dependence and significant increases among those who achieved full and partial remission from dependence. The increases in overall NBMCS and its social functioning, role emotional and mental health components were equally great for abstinent and nonabstinent remission from dependence, but improvements in bodily pain and general health were associated with nonabstinent remission only. Onset of abuse was unrelated to changes in QOL, and the increase in NBMCS associated with nonabstinent remission from abuse only was slight. Individuals with abuse only or no AUD who stopped drinking had significant declines in QOL. Conclusions: These results suggest the possible importance of preventing and treating AUD for maintaining and/or improving QOL. They are also consistent with the sick quitter hypothesis and suggest that abuse is less a mental disorder than a maladaptive pattern of behavior.
doi:10.1093/alcalc/agn094
PMCID: PMC2605522  PMID: 19042925
2.  Transitions In and Out of Alcohol Use Disorders: Their Associations with Conditional Changes in Quality of Life Over a 3-Year Follow-Up Interval 
Aims
To investigate longitudinal changes in quality of life (QOL) as a function of transitions in alcohol use disorders (AUD) over a 3-year follow-up of a general U.S. population sample.
Methods
The analysis is based on individuals who drank alcohol in the year preceding the Wave 1 National Epidemiologic Survey on Alcohol and Related Conditions and were reinterviewed at Wave 2 (n=22,245). Using multiple linear regression models, changes in SF-12 QOL were estimated as a function of DSM-IV AUD transitions, controlling for baseline QOL and multiple potential confounders.
Results
Onset and offset of AUD were strongly associated with changes in mental/psychological functioning, with significant decreases in mental component summary (NBMCS) scores among individuals who developed dependence and significant increases among those who achieved full and partial remission from dependence. The increases in overall NBMCS and its social functioning, role emotional and mental health components were equally great for abstinent and nonabstinent remission from dependence, but improvements in bodily pain and general health were associated with nonabstinent remission only. Onset of abuse was unrelated to changes in QOL, and the increase in NBMCS associated with nonabstinent remission from abuse only was slight. Individuals with abuse only or no AUD who stopped drinking had significant declines in QOL.
Conclusions
These results suggest the possible importance of preventing and treating AUD for maintaining and/or improving QOL. They are also consistent with the sick quitter hypothesis and suggest that abuse is less a mental disorder than a maladaptive pattern of behavior.
doi:10.1093/alcalc/agn094
PMCID: PMC2605522  PMID: 19042925
quality of life; QOL; HRQOL; alcohol use disorders; remission; transitions
3.  Neuroimaging of the Wernicke–Korsakoff Syndrome 
Aim: Presented is the neuroradiological signature of acute Wernicke's encephalopathy (WE), derived from different types of magnetic resonance imaging (MRI) sequences. WE results from thiamine depletion, and its most typical antecedent is chronic alcohol dependence. Brain regions observed with in vivo MRI affected in acute WE include the mammillary bodies, periaqueductal and periventricular gray matter, collicular bodies and thalamus. These affected areas are usually edematous and are best visualized and quantified with MRI sequences that highlight such tissue. Following the acute WE phase and resolution of edema and inflammation of affected brain tissue, WE, if not adequately treated with thiamine repletion, can herald Korsakoff's syndrome (KS), with its symptomatic hallmark of global amnesia, that is, the inability to commit newly encountered (episodic) information to memory for later recall or recognition. Methods: Neuropathology of KS detectable with MRI has a different neuroradiological signature from the acute stage and can be observed as tissue shrinkage or atrophy of selective brain structures, including the mammillary bodies and thalamus and ventricular expansion, probably indicative of atrophy of surrounding gray matter nuclei. Quantification of these and additional gray matter structures known to underlie global amnesia reveal substantial bilateral volume deficits in the hippocampus, in addition to the mammillary bodies and thalamus, and modest deficits in the medial septum/diagonal band of Broca. The infratentorium is also affected, exhibiting volume deficits in cerebellar hemispheres, anterior superior vermis and pons, contributing to ataxia of gait and stance. Results: Consideration of WKS structural brain changes in the context of the neuropathology of non-WKS alcoholism revealed a graded pattern of volume deficits, from mild in non-WKS alcoholics to moderate or severe in WKS, in the mammillary bodies, hippocampus, thalamus, cerebellum and pons. The development and resolution of brain structures affected in acute, chronic and treated WE was verified in longitudinal MRI study of rats that modeled of the interaction of extensive alcohol consumption and thiamine depletion and repletion. Conclusions: Thus, neuroradiological examination with MRI is valuable in the diagnosis of acute WE and enables in vivo tracking of the progression of the brain pathology of WE from the acute pathological phase to resolution with thiamine treatment or to progression to KS without treatment. Further, in vivo MRI facilitates translational studies to model antecedent conditions contributing to the development, sequelae and treatment of WE.
doi:10.1093/alcalc/agn103
PMCID: PMC2724861  PMID: 19066199
4.  Mechanisms of Neurodegeneration and Regeneration in Alcoholism 
Aims: This is a review of preclinical studies covering alcohol-induced brain neuronal death and loss of neurogenesis as well as abstinence-induced brain cell genesis, e.g. brain regeneration. Efforts are made to relate preclinical studies to human studies. Methods: The studies described are preclinical rat experiments using a 4-day binge ethanol treatment known to induce physical dependence to ethanol. Neurodegeneration and cognitive deficits following binge treatment mimic the mild degeneration and cognitive deficits found in humans. Various histological methods are used to follow brain regional degeneration and regeneration. Results: Alcohol-induced degeneration occurs due to neuronal death during alcohol intoxication. Neuronal death is related to increases in oxidative stress in brain that coincide with the induction of proinflammatory cytokines and oxidative enzymes that insult brain. Degeneration is associated with increased NF-κB proinflammatory transcription and decreased CREB transcription. Corticolimbic brain regions are most sensitive to binge-induced degeneration and induce relearning deficits. Drugs that block oxidative stress and NF-κB transcription or increase CREB transcription block binge-induced neurodegeneration, inhibition of neurogenesis and proinflammatory enzyme induction. Regeneration of brain occurs during abstinence following binge ethanol treatment. Bursts of proliferating cells occur across multiple brain regions, with many new microglia across brain after months of abstinence and many new neurons in neurogenic hippocampal dentate gyrus. Brain regeneration may be important to sustain abstinence in humans. Conclusions: Alcohol-induced neurodegeneration occurs primarily during intoxication and is related to increased oxidative stress and proinflammatory proteins that are neurotoxic. Abstinence after binge ethanol intoxication results in brain cell genesis that could contribute to the return of brain function and structure found in abstinent humans.
doi:10.1093/alcalc/agn079
PMCID: PMC2948812  PMID: 18940959
5.  Energy Intake Estimates of Respondent-Measured Alcoholic Beverages 
Aim:
The aim of this study was to demonstrate a methodology for estimating detailed energy intake from alcoholic beverages.
Methods:
Participants were 315 monthly drinkers who completed a drink-measuring exercise. Energy intake from alcohol and non-alcohol ingredients was calculated for all beverages consumed.
Results:
Measured alcoholic beverages had on average 140 kilocalories, with 26% of the energy coming from non-alcohol ingredients. The average monthly kilocalorie intake, from all alcoholic beverage types, was 6423 kilocalories. Self-measured wine and spirits drinks contained more energy than reference standards for size and ethanol concentration.
Conclusions:
Amount and sources of kilocalories differ by drink type, gender, age, education and BMI. Researchers and consumers should be aware of this variation and its sources.
doi:10.1093/alcalc/agn081
PMCID: PMC2605517  PMID: 18845529
6.  Energy Intake Estimates of Respondent-Measured Alcoholic Beverages 
Aim: The aim of this study was to demonstrate a methodology for estimating detailed energy intake from alcoholic beverages. Methods: Participants were 315 monthly drinkers who completed a drink-measuring exercise. Energy intake from alcohol and non-alcohol ingredients was calculated for all beverages consumed. Results: Measured alcoholic beverages had on average 140 kilocalories, with 26% of the energy coming from non-alcohol ingredients. The average monthly kilocalorie intake, from all alcoholic beverage types, was 6423 kilocalories. Self-measured wine and spirits drinks contained more energy than reference standards for size and ethanol concentration. Conclusions: Amount and sources of kilocalories differ by drink type, gender, age, education and BMI. Researchers and consumers should be aware of this variation and its sources.
doi:10.1093/alcalc/agn081
PMCID: PMC2605517  PMID: 18845529
7.  The Novel μ-Opioid Receptor Antagonist, [N-Allyl-Dmt1]Endomorphin-2, Attenuates the Enhancement of GABAergic Neurotransmission by Ethanol 
Aims: We investigated the effects of [N-allyl-Dmt1]endomorphin-2 (TL-319), a novel and highly potent μ-opioid receptor antagonist, on ethanol (EtOH)-induced enhancement of GABAA receptor-mediated synaptic activity in the hippocampus. Methods: Evoked and spontaneous inhibitory postsynaptic currents (eIPSCs and sIPSCs) were isolated from CA1 pyramidal cells from brain slices of male rats using whole-cell patch-clamp techniques. Results: TL-319 had no effect on the baseline amplitude of eIPSCs or the frequency of sIPSCs. However, it induced a dose-dependent suppression of an ethanol-induced increase of sIPSC frequency with full reversal at concentrations of 500 nM and higher. The non-specific competitive opioid receptor antagonist naltrexone also suppressed EtOH-induced increases in sIPSC frequency but only at a concentration of 60 μM. Conclusion: These data indicate that blockade of μ-opioid receptors by low concentrations of [N-allyl-Dmt1]endomorphin-2 can reverse ethanol-induced increases in GABAergic neurotransmission and possibly alter its anxiolytic or sedative effects. This suggests the possibility that high potency opioid antagonists may emerge as possible candidate compounds for the treatment of ethanol addiction.
doi:10.1093/alcalc/agn085
PMCID: PMC2724860  PMID: 18971291
8.  No Effect of Prenatal Alcohol Exposure on Activity in Three Inbred Strains of Mice 
Aims: Prenatal exposure to alcohol can have adverse effects on the developing fetus. Two of the hallmarks of children exposed to alcohol prenatally are attention deficits and hyperactivity. While hyperactivity has been observed in rats following prenatal ethanol exposure, few studies have examined these effects in mice. The present study investigated the effects of prenatal ethanol exposure on activity in mice from three inbred strains: C57BL/6 (B6), Inbred Long Sleep (ILS) and Inbred Short Sleep (ISS). Methods: On Days 7 through 18 of gestation, mice were intragastrically intubated twice daily with either 3.0 g/kg ethanol (E) or an isocaloric amount of maltose–dextrin (MD); non-intubated control (NIC) litters were also generated. Offspring activity was monitored at 30, 60, 90 and 150 days of age. Results: While results showed no effects of prenatal ethanol exposure on any measures of activity, we did observe differences in baseline activity among the strains. ISS mice were more active than B6 and ILS for all activity measures except stereotypy; B6 mice had higher measures of stereotypy than ILS and ISS. Younger mice were more active than older mice. The only sex effects were on measures of stereotypy, where males had higher scores. Conclusions: Mice are an excellent organism to study genetic influences on many phenotypes. However, our study and others have shown few effects of prenatal ethanol exposure on behavior in mice. It appears as if the prenatal period in mice, corresponding to organogenesis, is not a sensitive period for producing behavioral deficits following ethanol exposure. It is likely that the first 2 weeks postnatally, corresponding to the brain growth spurt, are more sensitive for producing behavioral effects.
doi:10.1093/alcalc/agn082
PMCID: PMC2724859  PMID: 18854366
9.  The Effects of Alcohol Abuse on Pulmonary Alveolar-Capillary Barrier Function in Humans 
Aims: Alcohol abuse is associated with the development of the acute respiratory distress syndrome, a disorder characterized by abnormal alveolar-capillary permeability. We hypothesized that individuals with a history of alcohol abuse would have clinical evidence of abnormal alveolar-capillary permeability even in the absence of symptoms. This could contribute to their propensity for the development of this disorder. Methods: Thirty-three subjects with a history of alcohol abuse, but no other medical problems, and 13 age- and smoking-matched controls inhaled 99mTc–DTPA (technetium-labeled diethylenetriamine penta-acetate; an isotope used to measure lung permeability) for a 3-min period, and washout of this isotope was measured for a 90-min period. The rate at which it was cleared from the lungs was assessed and compared between subjects and controls. Results: The half-life of 99mTc–DTPA in the lungs of subjects with alcohol abuse was significantly shorter than that observed in matched controls, even when correcting for the effects of concomitant tobacco use. When the half-life of the isotope for smoking alcohol-abusing subjects and smoking controls were compared separately, there was a trend for the alcohol-abusing subjects to have a shorter half-life of the isotope present in the lungs. This was also true when non-smokers were compared. Conclusions: These observations provide further evidence that alcohol abuse affects the normal permeability of the alveolar-capillary barrier and thereby may contribute to the development of the acute respiratory distress syndrome in individuals with alcohol abuse.
doi:10.1093/alcalc/agn051
PMCID: PMC2724858  PMID: 18567916
10.  Combined Neuroimaging, Neurocognitive and Psychiatric Factors to Predict Alcohol Consumption Following Treatment for Alcohol Dependence 
Aims: Resumption of hazardous drinking after treatment is common in alcohol use disorders (AUD). This study examined the ability of multimodality magnetic resonance, neurocognitive, psychiatric and demographic, to predict alcohol consumption after treatment for AUD. Methods: Seventy treatment-seeking participants completed 1.5T magnetic resonance studies, yielding regional gray matter (GM) and white matter (WM) surrogate markers of neuronal integrity (N-acetylaspartate: NAA) and cell membrane turnover/synthesis (choline: Cho), assessment of major psychiatric disorders and comprehensive neurocognitive assessment after ∼1 month of abstinence. Participants were followed up 6–12 months after treatment and classified as Abstainers (no alcohol consumption; n = 26) and Resumers (any alcohol consumption; n = 44). Abstainers and Resumers were contrasted on various outcome measures, and those that significantly differed between groups were entered as factors in a logistical regression model to predict drinking status at follow-up. Results: The following variables were independent predictors of resumption of drinking: temporal GM NAA, frontal WM NAA, frontal GM Cho, processing speed and comorbid unipolar mood disorder. With each standard deviation unit decrease in temporal GM NAA, frontal WM NAA, frontal GM Cho and processing speed, the odds of resumption of drinking were increased 3.1, 3.3, 6.4 and 14.2 times, respectively. Diagnosis of a unipolar mood disorder was associated with 14.5-fold increased odds of resumed drinking. Conclusions: The findings suggest that Resumers, relative to Abstainers, demonstrated greater abnormalities in anterior frontal-subcortical circuits involved in mood and behavioral regulation, and development and maintenance of alcohol use disorders, The magnetic resonance-derived variables used in this study may provide additional information regarding the prediction and neurobiological correlates of resumption of hazardous drinking.
doi:10.1093/alcalc/agn078
PMCID: PMC2720770  PMID: 18818189
11.  The Self-Rating of the Effects of Alcohol Questionnaire as a Predictor of Alcohol-Related Outcomes in 12-Year-Old Subjects 
Aims: A low level of response (LR), or low sensitivity, to alcohol as established by alcohol challenges has been shown to predict future heavier drinking, alcohol-related problems and alcohol use disorders. To date, only one study has evaluated the predictive validity of a second measure of LR as determined by the Self-Report of the Effects of Alcohol (SRE) Questionnaire. The current analyses evaluate the ability of SRE scores as determined at age 12 to predict heavier drinking and alcohol-related problems 2 years later in a sample from the United Kingdom. Methods: The subjects were 156 boys (54.5%) and girls from the Avon Longitudinal Study of Parents and Children (ALSPAC) who had reported consuming one or more standard drinks by age 12 and who were followed up 2 years later. Results: The age 12 SRE scores correlated with the number of drinks per week, maximum drinks and the number of alcohol problems both at baseline and at age 14 follow-ups. In these evaluations, a larger number of drinks required for effects on the SRE (i.e. a lower LR per drink consumed) related to heavier intake and alcohol-related difficulties. Simultaneous entry multiple regression analyses revealed that the age 12 SRE score maintained a significant relationship with age 14 higher number of drinks per week and the number of alcohol problems even when the age 12 values for alcohol intake and problems were used as covariates. Conclusion: The SRE scores appear to have value in predicting future heavier drinking and alcohol problems in 12-year olds that go beyond the information offered by the earlier drinking pattern alone.
doi:10.1093/alcalc/agn077
PMCID: PMC2720769  PMID: 18845530
12.  Not All Drinks Are Created Equal: Implications for Alcohol Assessment in India 
Aims: There is sparse literature on drink alcohol content in developing countries. This study documented detailed information on drink sizes and ethanol content of alcoholic beverages consumed in three different parts of India. Methods: Data primarily from formative phases of studies on alcohol use patterns in the states of Delhi, Rajasthan and Goa are reported. Participant observation and semi-structured interviews with key informants and drinking respondents were used to assess different beverage types and to empirically measure actual drink sizes as poured. Investigation of ethanol content included the use of biochemical analyses, the alcoholmeter and the Analox Analyser AM3. Respondents interviewed in the post-formative phase in one study were also asked to define the volume of their drinks by indicating pour levels in select drinking vessels. Results: A wide range of alcoholic drinks were documented that varied in ethanol concentration across and within sites. Drink sizes, particularly for high-strength beverages, varied both by study site and respondent, with pours of distilled spirits on average being larger than standard measures. Conclusion: Estimates of both mean volume of alcohol consumption and heavy drinking amounts are influenced by variability in alcohol concentration and respondent-defined pour sizes. The variation in drink alcohol content found across Indian states indicates that prior to conducting quantitative surveys, preliminary work on sources of drink alcohol content variation should be undertaken to tailor measurement tools to specific beverages and drinking practices observed. Recommendations for alcohol research in developing countries are provided.
doi:10.1093/alcalc/agn074
PMCID: PMC2720768  PMID: 18832137
13.  Alcohol Abuse/Dependence Symptoms Among Hospital Employees Exposed to a SARS Outbreak 
Aims: The aim of this study was to examine alcohol abuse/dependence symptoms among hospital employees exposed to a severe acute respiratory syndrome (SARS) outbreak, and the relationship between types of exposure to the SARS outbreak and subsequent alcohol abuse/dependence symptoms. Methods: A survey was conducted among 549 randomly selected hospital employees in Beijing, China, concerning the psychological impact of the 2003 SARS outbreak. Subjects were assessed on sociodemographic factors and types of exposure to the outbreak, and on symptoms of post-traumatic stress (PTS), alcohol abuse/dependence and depression. Results: Current alcohol abuse/dependence symptom counts 3 years after the outbreak were positively associated with having been quarantined, or worked in high-risk locations such as SARS wards, during the outbreak. However, having had family members or friends contract, SARS was not related to alcohol abuse/dependence symptom count. Symptoms of PTS and of depression, and having used drinking as a coping method, were also significantly associated with increased alcohol abuse/dependence symptoms. The relationship between outbreak exposure and alcohol abuse/dependence symptom count remained significant even when sociodemographic and other factors were controlled for. When the intrusion, avoidance and hyperarousal PTS symptom clusters were entered into the model, hyperarousal was found to be significantly associated with alcohol abuse/dependence symptoms. Conclusions: Exposure to an outbreak of a severe infectious disease can, like other disaster exposures, lead not only to PTSD but also to other psychiatric conditions, such as alcohol abuse/dependence. The findings will help policy makers and health professionals to better prepare for potential outbreaks of diseases such as SARS or avian flu.
doi:10.1093/alcalc/agn073
PMCID: PMC2720767  PMID: 18790829
14.  Addictions Biology: Haplotype-Based Analysis for 130 Candidate Genes on a Single Array 
Aims: To develop a panel of markers able to extract full haplotype information for candidate genes in alcoholism, other addictions and disorders of mood and anxiety. Methods: A total of 130 genes were haplotype tagged and genotyped in 7 case/control populations and 51 reference populations using Illumina GoldenGate SNP genotyping technology, determining haplotype coverage. We also constructed and determined the efficacy of a panel of 186 ancestry informative markers. Results: An average of 1465 loci were genotyped at an average completion rate of 91.3%, with an average call rate of 98.3% and replication rate of 99.7%. Completion and call rates were lowered by the performance of two datasets, highlighting the importance of the DNA quality in high throughput assays. A comparison of haplotypes captured by the Addictions Array tagging SNPs and commercially available whole-genome arrays from Illumina and Affymetrix shows comparable performance of the tag SNPs to the best whole-genome array in all populations for which data are available. Conclusions: Arrays of haplotype-tagged candidate genes, such as this addictions-focused array, represent a cost-effective approach to generate high-quality SNP genotyping data useful for the haplotype-based analysis of panels of genes such as these 130 genes of interest to alcohol and addictions researchers. The inclusion of the 186 ancestry informative markers allows for the detection and correction for admixture and further enhances the utility of the array.
doi:10.1093/alcalc/agn032
PMCID: PMC2724863  PMID: 18477577
15.  Alcohol exposure alters cell cycle and apoptotic events during early neurulation 
Background: Fetal alcohol exposure causes growth deficits, microencephaly, and neurological abnormalities. Although the effects of alcohol on developmental delay and growth-related deficits have been hypothesized, little is understood about how alcohol alters, in particular, the cyclin pathway within the cell cycle, which is critical to proliferation and apoptotic control. In this study, we examined cell cycle proteins pertinent to the G1–S phase transition and apoptosis, to determine if cell cycle misregulation can be attributed to apoptotic induction and growth defects. Methods: We examined cell cycle regulation during G1 and S-phase, and DNA fragmentation damage, using E14 dorsal root ganglia neural stem cells (DRG-NC), and cultured mouse embryos exposed to 200 and 400 mg/dl ethanol. Results: Alcohol-exposed DRG-NC demonstrated a dose-dependent increase in cells expressing increased cyclin D1 protein, and increased DNA fragmentation. Western blot analysis, using embryos, demonstrated an overexpression of cyclin D1, D2, and E2F1, key G1 to S-phase cell cycle regulatory components, and increases in p53, linking the cell cycle and apoptotic pathways. Bromodeoxyuridine incorporation indicated reduced DNA synthesis and growth in several embryonic regions. Propidium iodide staining demonstrated decreases in DNA content and increases in DNA fragmentation in several embryonic tissues. Conclusions: This study indicated that retarded growth of DRG-NC and embryos, induced by alcohol, is associated with altered expression of cell cycle and apoptotic proteins and concurrent inhibition of proliferation and increased DNA fragmentation. We suggest that alcohol induces an increase in cyclin D1 expression, premature S-phase entry, and disjointed DNA synthesis with increased apoptosis.
doi:10.1093/alcalc/agm166
PMCID: PMC2899941  PMID: 18283098

Results 1-15 (15)