Changes in the Episodic Memory and Executive Functions of Abstinent and Relapsed Alcoholics Over a 6-Month Period

Background: It is still unclear whether episodic memory and executive functions capacities can return to normal in abstinent patients over a 6‐month period. Furthermore, the role of interim drinking in cognitive recovery is still not well known. Finally, further research is required to specify the predictive value of cognitive abilities at initial testing in the treatment outcome (abstinence or relapse) . The aims of the present study were therefore to measure changes in episodic memory and executive functions over a 6‐month period in abstinent and relapsed alcoholics and to ascertain whether neuropsychological results at treatment entry can predict treatment outcome at follow‐up. Methods: Fifty‐four alcoholic patients and 54 matched control subjects performed baseline neuropsychological tasks assessing episodic memory, executive functions, the slave systems of working memory and attentional abilities. At the follow‐up session (i.e., 6 months later), episodic memory and 3 executive functions (inhibition, flexibility, and updating) were re‐examined in the alcoholic patients. Results: Results showed that over the 6‐month interval, the abstainers’ episodic memory and executive performances had returned to normal, whereas the relapsers performed lower than before in the flexibility task. Episodic memory and executive functions recovery was correlated, in abstainers, with drinking history and age respectively. Finally, there was no significant difference regarding neuropsychological scores at baseline between abstainers and relapsers. Discussion: Over the 6‐month interval, abstainers normalized episodic memory and executive performances whereas relapsers obtained executive results which were more severely impaired, emphasizing the influence of interim drinking on cognitive changes. Episodic memory, executive functions, the slave systems of working memory and attentional abilities did not appear to be reliable predictors of treatment outcome over a 6‐month interval.     

Sleep electroencephalographic spectral power after withdrawal from alcohol in alcohol-dependent patients

BACKGROUND: Dysfunctional hyperarousal is suspected to be a neurophysiological determinant of relapse in abstinent alcohol-dependent patients. In the present study, we used spectral power analysis of the sleep electroencephalographic (EEG) to quantify brain activity during sleep in patients during subacute withdrawal as well as in control subjects. Our hypothesis was that the subgroup of patients who relapsed within the 3 months to follow-up would exhibit-increased dysfunctional arousal manifested by higher-frequency (beta) EEG power during sleep. METHODS: Twenty-six alcohol-dependent in-patients were examined with polysomnography over 2 nights 2 to 3 weeks after withdrawal. At the 3-month clinical follow-up assessment, 12 of them had relapsed and 14 abstained. The control group consisted of 23 healthy subjects similar to the patients with alcohol dependence in age and gender distribution. Spectral sleep EEG analysis was performed on both nights (adaptation and baseline) of all subjects. Logarithmic artifact-controlled spectral band power of sleep stage 2 and rapid eye movement (REM) sleep was analyzed for Group, Gender, and Age effects using multiple analyses of covariance. Three groups were compared with the Group factor: relapsers, abstainers, and controls. RESULTS: Generally, both Group and Age effects were significant for the second, baseline night for the visually scored sleep parameters, while spectral EEG parameters showed significant differences in the adaptation night. In the adaptation night, a significant enhancement in the beta2 band (24-32 Hz) was seen in REM sleep in relapsers relative to both abstainers and controls. CONCLUSIONS: The beta2 increase could be interpreted as a sign of dysfunctional arousal during REM sleep "unmasked" by the additional stressor of sleep environment adaptation. Its determinants are likely to be both premorbid and drinking history related.     

Reduced cortical thickness in abstinent alcoholics and association with alcoholic behavior

Background: Chronic misuse of alcohol results in widespread damage to the brain. Prior morphometric studies have examined cortical atrophy in individuals with alcoholism; however, no previous studies have examined alcohol‐associated atrophy using cortical thickness measurements to obtain regional mapping of tissue loss across the full cortical surface. Methods: We compared cortical thickness measures from 31 abstinent individuals with a history of prior alcohol abuse to 34 healthy nonalcoholic control participants (total sample size = 65). Cortical surface models were created from high‐resolution T1‐weighted images, and cortical thickness was then estimated as the distance between the gray matter/white matter boundary and the outer cortical surface. Results: Abstinent alcoholics showed reduced whole‐brain thickness as compared to nonalcoholic participants. Decreases in thickness were found bilaterally in (i) superior frontal, (ii) precentral, (iii) postcentral, (iv) middle frontal, (v) middle/superior temporal, (vi) middle temporal, and (vii) lateral occipital cortical regions. Decreased cortical thickness in the alcoholic group was associated with severity of alcohol abuse. Conclusions: These findings demonstrate widespread reduction in cortical thickness as a consequence of chronic alcoholism, with most severe reductions in frontal and temporal brain regions.     

Longitudinal Changes in Magnetic Resonance Imaging Brain Volumes in Abstinent and Relapsed Alcoholics

Chronic alcoholism is associated with smaller volumes of cortical gray matter and white matter and a complementary increase in brain cerebrospinal fluid (CSF) volumes, relative to age norms. This longitudinal study quantified the extent of brain volume changes associated with abstinence and drinking at three time points in chronic alcoholics. We obtained magnetic resonance imaging (MRI) on 58 alcoholic men after an average of 12 days (MRI-1) and 32 days (MRI-2) of sobriety. In addition, 58 healthy control subjects were scanned at a comparable interval. At MRI-3, 11 controls and 39 alcoholics were rescanned, 2–12 months after MRI-2; 19 alcoholics had abstained, and 20 had resumed drinking. Axial MRI slices were segmented into cortical gray matter, white matter, and CSF and summed over seven slices; lateral and third ventricular volumes were also estimated. MRI volume changes were corrected using an estimate of interscan measurement error caused by head positioning differences, and then divided by the interval to yield rates of change (slopes). From MRI-1 to MRI-2, the alcoholic group showed declines in CSF volumes of the lateral ventricles and posterior cortical sulci, and a trend toward an increase in anterior cortical gray matter volume relative to the control group. From MRI-2 to MRI-3, third ventricular volumes decreased in the abstainers relative to the relapsers and controls; cortical white matter volume decreased in the relapsers. In the relapsers, lifetime consumption of alcohol (as of MRI-1) predicted later vulnerability to white matter volume decline and third ventricular enlargement with resumption of drinking. These data suggest that improvement in cortical gray matter, sulcal, and lateral ventricular volumes occur early in the course of abstinence, and that improvement in third ventricular volume appears later with continued abstinence. Resumption of drinking after a short period of abstinence arrests third ventricular volume improvement and produces white matter volume loss.     

An analysis of the abstinence violation effect in a sample of illicit drug users

Studies using samples of alcoholics and cigarette smokers show that the occurrence of the abstinence violation effect predicts the likelihood of a full-blown relapse following an initial slip from voluntary abstinence. The present study investigated this process in a sample of 31 illicit drug users. The attributional styles of abstainers and relapsers were examined in addition to the types of initial slip situations for the relapse group. No significant differences were found in attributional styles, although relative to the relapse group there was a tendency for abstainers to score higher on intemality and stability of attribution for negative events, but lower on globality. Both negative affect and interpersonal conflict, but not social pressure, were found to be important precipitants for relapse. Demographic differences between the groups are discussed in addition to the implications of the results for models of relapse, prediction of relapse and cognitive therapy in relapse prevention.     

Effects of cigarette smoking or nicotine replacement on cardiovascular risk factors and parameters of haemorheology

OBJECTIVES: Cigarette smoking causes cardiovascular (CV) disease, but the relative roles of nicotine and other components of tobacco smoke remain unclear. We investigated the effect of stopping smoking, by using nicotine replacement therapy (NRT), on haemorheology parameters. DESIGN: Open, parallel-group trial (intervention group and control smokers). SETTING: Clinic within university department of pharmacology. SUBJECTS: One hundred and ninety-seven males, aged 25-45 years, smoking >20 cigarettes per day. INTERVENTIONS: One hundred and sixty-four subjects were instructed to stop smoking and received NRT for 12 weeks and 33 acted as controls. After 12 weeks, NRT was discontinued, and all subjects were followed-up at 26 weeks. At the end of the study, the NRT group was divided into abstainers (self-reported, verified by exhaled carbon monoxide <10 ppm) and relapsers, who were unable to remain abstinent. MAIN OUTCOME MEASURES: Plasma viscosity, fibrinogen, erythrocyte deformability, reactive capillary blood flow, transcutaneous partial oxygen tension (tcpO2) and haematocrit, assessed at 4, 8, 12, and 26 weeks. Results. After 6 months, plasma fibrinogen (9.95 vs. 8.24 micromol x L(-1) at baseline; P < 0.003), reactive capillary flow (t-pmax: 9.3 vs. 11.2 s at baseline; P < 0.005), and tcpO2 (50.4 vs. 34.9 mmHg at baseline; P < 0.0001) were significantly improved in abstainers, but changes in plasma viscosity and erythrocyte deformability were inconclusive. Other CV risk factors, such as haematocrit and white blood cell count, decreased to a greater extent in abstainers than in relapsers. Expired carbon monoxide concentrations reflected the changes in smoking and decreased in abstainers from 30.4 ppm at baseline to 4.2 ppm; P < 0.0001). Conclusions. Smoking cessation improved CV parameters, and use of nicotine medications did not negate these improvements.     

Effects of Abstinence on the Brain: Quantitative Magnetic Resonance Imaging and Magnetic Resonance Spectroscopic Imaging in Chronic Alcohol Abuse

Background: Structural brain damage, especially to white matter, is well documented in chronic alcohol abuse. There is also evidence for brain metabolic abnormalities in this condition. It is unknown, however, to what extent these structural and metabolic changes are present in treated alcohol abusers who achieve long-term abstinence versus treatment-naïve, heavily drinking individuals. Methods: This study compared 12 recovering alcoholics with 8 actively heavily drinking subjects. Participants underwent magnetic resonance (MR) imaging and proton MR spectroscopic imaging of the brain. Semiautomated image segmentation techniques yielded volumes for gray matter, white matter, white matter lesions, and cerebral spinal fluid in multiple brain regions defined by Talairach stereotaxic coordinates. Automated spectral processing methods yielded gray and white matter concentrations of the metabolites N-acetylaspartate, creatine, and choline for the same regions. Results: Recovering alcoholics had greater volumes of frontal white matter, but the opposite was true for white matter in a “remainder” region encompassing the basal frontal and temporal lobes, the cerebellum, and the brainstem. Recovering alcoholics also had smaller volumes of white matter lesions in whole brain, in occipital and mesial parietal regions, and in the remainder region. Recovering alcoholics had greater gray matter volumes in the orbital frontal pole and postcentral gyrus, but smaller gray matter volumes in the anterior cingulate. Whole-brain and regional metabolite concentrations did not differ significantly between the two groups. Conclusions: White and gray matter volumes in different regions of the brain were greater or smaller in recovering, treated alcoholics. The findings suggest region-specific structural recovery from chronic alcohol–induced brain injury, but also region-specific long-term structural damage in abstinent alcoholics. White matter lesions were widespread in active drinkers and may partly resolve during long-term abstinence. Proton MR spectroscopic measures, as applied in this cross-sectional study, were largely ineffective in revealing metabolic effects of abstinence on the alcohol-damaged brain.     

Smoking habits in relapsed subjects from a smoking cessation trial after one year

Reports of smoking cessation studies often claim that many relapsed subjects reduce their smoking. We investigated the smoking habits of relapsers 1 year after quitting in a smoking cessation trial using nicotine or placebo patches. All 289 participants in that study were summoned to a 1-year follow-up visit–148 (57%) of 259 relapsers attended, as did all 30 sustained abstainers. Fewer than 1% of the subjects had quit spontaneously after the primary relapse. Daily cigarette consumption, standard nicotine yield per cigarette, saliva cotinine concentration, expired carbon monoxide level and two nicotine dependency scales were assessed at entry and at the 1-year follow-up. In five of these six smoking-related characteristics, there was a small but significant mean reduction of 7%-27%. A significant weight gain of 0.5 ± 2.9 kg (mean ± SD) was recorded in the relapsers compared with 4.8 ± 4.2 kg for abstainers (p < 0.001). It is concluded that smoking habits in relapsers are relatively unchanged, and thus the most important outcome measure in smoking cessation trials is abstinent subjects.     

Abstention, alcohol use and risk of myocardial infarction in men and women taking account of social support and working conditions: the SHEEP case-control study

Aims Very few studies indicating that low–moderate alcohol consumption protects from myocardial infarction (MI) controlled for social support and working conditions, which could confound the findings. Therefore, a first aim was to study the risk of non‐fatal and total MI in relation to volume of alcohol consumption and measures of social support and working conditions. A second aim was to analyse the impact of the volume of earlier alcohol use in abstainers. Design Data came from a case–control study, the Stockholm Heart Epidemiology Program (SHEEP), including first MI among Swedish citizens 45–70 years old. Setting Stockholm County 1992–94. Participants There were 1095 cases of MI in men and 471 in women (928 and 372 were non‐fatal), and 2339 living controls from the general population. Measurement Information about alcohol use at different periods in life and job strain, social anchorage and life control besides pre‐existing health problems, smoking, physical activity, socio‐economic status and marital status was obtained by a questionnaire from the cases and the controls. Findings In multivariate logistic regression analyses, the relative risk for MI (especially non‐fatal) was reduced among alcohol consumers. RR for non‐fatal MI was 0.52 (95% confidence intervals 0.32, 0.85) in men with a consumption of 50–69.9 g 100% ethanol/day and 0.21 (95% confidence interval 0.06, 0.77) in women with a consumption of 30 g or more per day (reference category 0.1–5 g 100% ethanol/day). Men who were abstainers during the previous 1–10 years and with an earlier average consumption of 5–30 g 100% ethanol/day had a significantly lower relative risk compared to such abstainers with an earlier higher consumption. Earlier consumption among abstainers may also have an impact on gender differences in MI. Analyses showed positive interaction between abstention and low life‐control in women, but only 4% of the female cases were due to this interaction. There were no other interactions between measures of alcohol use and social anchorage, life control and working situations. Conclusion Alcohol use had a protective impact on MI, with little impact of job strain, social anchorage and life control, giving increased support for a protective impact of low‐moderate alcohol use. The level of previous alcohol consumption among male 1–10‐year‐long abstainers influenced the risk of MI.     

Rates and correlates of relapse among individuals in remission from DSM-IV alcohol dependence: a 3-year follow-up

Background: There is little information on the stability of abstinent and nonabstinent remission from alcohol dependence in the general U.S. population. The aim of this study was to examine longitudinal changes in recovery status among individuals in remission from DSM‐IV alcohol dependence, including rates and correlates of relapse, over a 3‐year period. Methods: This analysis is based on data from Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a nationally representative sample of U.S. adults aged 18 years and older originally interviewed in 2001 to 2002 and reinterviewed in 2004 to 2005. The Wave 1 NESARC identified 2,109 individuals who met the DSM‐IV criteria for full remission from alcohol dependence. Of these, 1,772 were reinterviewed at Wave 2, comprising the analytic sample for this study. Recovery status at Wave 2 was examined as a function of type of remission at Wave 1, with a focus on rates of relapse, alternately defined as recurrence of any alcohol use disorder (AUD) symptoms and recurrence of DSM‐IV alcohol dependence. Logistic regression models were used to estimate the odds of relapse among asymptomatic risk drinkers and low‐risk drinkers relative to abstainers, adjusted for a wide range of potential confounders. Results: By Wave 2, 51.0% of the Wave 1 asymptomatic risk drinkers had experienced the recurrence of AUD symptoms, compared with 27.2% of low‐risk drinkers and 7.3% of abstainers. Across all ages combined, the adjusted odds of recurrence of AUD symptoms relative to abstainers were 14.6 times as great for asymptomatic risk drinkers and 5.8 times as great for low‐risk drinkers. The proportions of individuals who had experienced the recurrence of dependence were 10.2, 4.0, and 2.9%, respectively, and the adjusted odds ratios relative to abstainers were 7.0 for asymptomatic risk drinkers and 3.0 for low‐risk drinkers. Age significantly modified the association between type of remission and relapse. Differences by type of remission were not significant for younger alcoholics, who had the highest rates of relapse. Conclusions: Abstinence represents the most stable form of remission for most recovering alcoholics. Study findings highlight the need for better approaches to maintaining recovery among young adults in remission from alcohol dependence, who are at particularly high risk of relapse.     

Peptidergic agonists of activity-dependent neurotrophic factor protect against prenatal alcohol-induced neural tube defects and serotonin neuron loss

Introduction: Prenatal alcohol exposure via maternal liquid diet consumption by C57BL/6 (B6) mice causes conspicuous midline neural tube deficit (dysraphia) and disruption of genesis and development of serotonin (5‐HT) neurons in the raphe nuclei, together with brain growth retardation. The current study tested the hypothesis that concurrent treatment with either an activity‐dependent neurotrophic factor (ADNF) agonist peptide [SALLRSIPA, (SAL)] or an activity‐dependent neurotrophic protein (ADNP) agonist peptide [NAPVSIPQ, (NAP)] would protect against these alcohol‐induced deficits in brain development. Methods: Timed‐pregnant B6 dams consumed alcohol from embryonic day 7 (E7, before the onset of neurulation) until E15. Fetuses were obtained on E15 and brain sections processed for 5‐HT immunocytochemistry, for evaluation of morphologic development of the brainstem raphe and its 5‐HT neurons. Additional groups were treated either with SAL or NAP daily from E7 to E15 to assess the potential protective effects of these peptides. Measures of incomplete occlusion of the ventral canal and the frequency and extent of the openings in the rhombencephalon were obtained to assess fetal dysraphia. Counts of 5‐HT‐immunostained neurons were also obtained in the rostral and caudal raphe. Results: Prenatal alcohol exposure resulted in abnormal openings along the midline and delayed closure of ventral canal in the brainstem. This dysraphia was associated with reductions in the number of 5‐HT neurons both in the rostral raphe nuclei (that gives rise to ascending 5‐HT projections) and in the caudal raphe (that gives rise to the descending 5‐HT projections). Concurrent treatment of the alcohol‐consuming dams with SAL prevented dysraphia and protected against the alcohol‐induced reductions in 5‐HT neurons in both the rostral and caudal raphe. NAP was less effective in protecting against dysraphia and did not protect against 5‐HT loss in the rostral raphe, but did protect against loss in the caudal raphe. Conclusions: These findings further support the potential usefulness of these peptides for therapeutic interventions in pregnancies at risk for alcohol‐induced developmental deficits. Notably, the ascending 5‐HT projections of the rostral raphe have profound effects in regulating forebrain development and function, and the descending 5‐HT projections of the caudal raphe are critical for regulating respiration. Protection of the rostral 5‐HT‐system may help prevent structural and functional deficits linked to abnormal forebrain development, and protection of the caudal systems may also reduce the increased risk for sudden infant death syndrome associated with prenatal alcohol exposure.     

High predictive value of early viral kinetics in retreatment with peginterferon and ribavirin of chronic hepatitis C patients non-responders to standard combination therapy

BACKGROUND/AIMS: To evaluate the efficacy of peginterferon alfa-2b and ribavirin in unselected consecutive patients with chronic hepatitis C, treated outside of trials, who were relapsers or non-responders to interferon and ribavirin combination. METHODS: One hundred and fifty-four patients were evaluated. There were 101 non-responders and 53 relapsers to standard combination therapy. Patients were retreated with peginterferon alfa-2b 1.5 microg/kg/wk plus ribavirin 1000-1200 mg/day during 48 weeks. RESULTS: Forty-four patients (28.6%) achieved sustained virological response (SVR). Rapid (week 4) and early (week 12) virological response had high negative predictive values of SVR (94% and 97%, respectively); however positive predictive values were relatively low (52% and 49%, respectively). Relapsers had higher SVR rates (58.5%) than non-responders (13%) p<0.0001. In non-responders, SVR raised to 50% in patients with genotype non-1 and mild or moderate fibrosis. In multivariate analysis, predictors of SVR were: relapse after interferon plus ribavirin combination, mild or moderate fibrosis, genotype non-1 and baseline viral load <2 million copies/ml. CONCLUSIONS: Relapsers to interferon plus ribavirin therapy, and non-responders with genotype non-1 and mild or moderate fibrosis, achieved a relatively high SVR rate following retreatment with peginterferon plus ribavirin. Early viral kinetics had a high negative predictive value of SVR.     

Magnetic Resonance Imaging Volume of the Angular Gyri Predicts Financial Skill Deficits in People with Amnestic Mild Cognitive Impairment

OBJECTIVES: To better understand how brain atrophy in amnestic mild cognitive impairment (MCI) as measured using magnetic resonance imaging (MRI) volumetrics could affect instrumental activities of daily living (IADLs) such as financial abilities. DESIGN: Controlled, matched‐sample, cross‐sectional analysis regressing MRI volumetrics with financial performance measures. SETTING: University medical and research center. PARTICIPANTS: Thirty‐eight people with MCI and 28 older adult controls. MEASUREMENTS: MRI volumetric measurement of the hippocampi, angular gyri, precunei, and medial frontal lobes. Participants also completed neuropsychological tests and the Financial Capacity Instrument (FCI). RESULTS: Correlations were performed between FCI scores and MRI volumes in the group with MCI. People with MCI performed significantly below controls on the FCI and had significantly smaller hippocampi. Among people with MCI, performance on the FCI was moderately correlated with angular gyri and precunei volumes. Regression models demonstrated that angular gyrus volumes were predictive of FCI scores. Tests of mediation showed that measures of arithmetic and possibly attention partially mediated the relationship between angular gyrus volume and FCI score. CONCLUSION: Impaired financial abilities in amnestic MCI correspond with volume of the angular gyri as mediated by arithmetic knowledge. The findings suggest that early neuropathology within the lateral parietal region in MCI leads to a breakdown of cognitive abilities that affect everyday financial skills. The findings have implications for diagnosis and clinical care of people with MCI and AD.     

Subcortical volumes in long-term abstinent alcoholics: associations with psychiatric comorbidity

Background: Research in chronic alcoholics on memory, decision‐making, learning, stress, and reward circuitry has increasingly highlighted the importance of subcortical brain structures. In addition, epidemiological studies have established the pervasiveness of co‐occurring psychiatric diagnoses in alcoholism. Subcortical structures have been implicated in externalizing pathology, including alcohol dependence, and in dysregulated stress and reward circuitry in anxiety and mood disorders and alcohol dependence. Most studies have focused on active or recently detoxified alcoholics, while subcortical structures in long‐term abstinent alcoholics (LTAA) have remained relatively uninvestigated. Methods: Structural MRI was used to compare volumes of 8 subcortical structures (lateral ventricles, thalamus, caudate, putamen, pallidum, hippocampus, amygdala, and nucleus accumbens) in 24 female and 28 male LTAA (mean abstinence = 6.3 years, mean age = 46.6 years) and 23 female and 25 male nonalcoholic controls (NAC) (mean age = 45.6 years) to explore relations between subcortical brain volumes and alcohol use measures in LTAA and relations between subcortical volumes and psychiatric diagnoses and symptom counts in LTAA and NAC. Results: We found minimal differences between LTAA and NAC in subcortical volumes. However, in LTAA, but not NAC, volumes of targeted subcortical structures were smaller in individuals with versus without comorbid lifetime or current psychiatric diagnoses, independent of lifetime alcohol consumption. Conclusions: Our finding of minimal differences in subcortical volumes between LTAA and NAC is consistent with LTAA never having had volume deficits in these regions. However, given that imaging studies have frequently reported smaller subcortical volumes in active and recently detoxified alcoholics compared to controls, our results are also consistent with the recovery of subcortical volumes with sustained abstinence. The finding of persistent smaller subcortical volumes in LTAA, but not NAC, with comorbid psychiatric diagnoses, suggests that the smaller volumes are a result of the combined effects of chronic alcohol dependence and psychiatric morbidity and suggests that a comorbid psychiatric disorder (even if not current) interferes with the recovery of subcortical volumes.     

Drinking pattern and risk of non-fatal myocardial infarction: a population-based case-control study

Aims Alcohol consumption has been associated with a reduced risk of heart disease incidence and mortality. However, most studies have focused on an average volume per specific time period and have paid little attention to the pattern of drinking. The aim of this study was to examine the association between various drinking patterns and myocardial infarction (MI). Design A population‐based case–control study. Methods Participants were 427 white males with incident MI and 905 healthy white male controls (age 35–69 years) selected randomly from two Western New York counties. During computer‐assisted interviews detailed information was collected regarding patterns of alcohol consumption during the 12–24 months prior to interview (controls) or MI (cases). Findings Compared to life‐time abstainers, adjusted odds ratios (ORs) and 95% confidence interval (CI) for non‐current and current drinkers were 0.66 (0.31–1.39) and 0.50 (0.24–1.02), respectively. Daily drinkers exhibited a significantly lower OR (0.41) compared to life‐time abstainers. Participants who drank mainly without food had an OR of 1.49 (0.96–2.31) compared to those who drank mainly with food and 0.62 (0.28–1.37) compared to life‐time abstainers. Men who reported drinking only at weekends had a significantly greater MI risk [1.91; (1.21–3.01)] compared to men who drank less than once/week, but not compared to life‐time abstainers [0.91 (0.40–2.07)]. Conclusions Our results indicate that patterns of alcohol use have important cardiovascular health implications.     

Striatal involvement in human alcoholism and alcohol consumption, and withdrawal in animal models

Background: Different regions of the striatum may have distinct roles in acute intoxication, alcohol seeking, dependence, and withdrawal. Methods: The recent advances are reviewed and discussed in our understanding of the role of the dorsolateral striatum (DLS), dorsomedial striatum (DMS), and ventral striatum in behavioral responses to alcohol, including alcohol craving in abstinent alcoholics, and alcohol consumption and withdrawal in rat, mouse, and nonhuman primate models. Results: Reduced neuronal activity as well as dysfunctional connectivity between the ventral striatum and the dorsolateral prefrontal cortex is associated with alcohol craving and impairment of new learning processes in abstinent alcoholics. Within the DLS of mice and nonhuman primates withdrawn from alcohol after chronic exposure, glutamatergic transmission in striatal projection neurons is increased, while GABAergic transmission is decreased. Glutamatergic transmission in DMS projection neurons is also increased in ethanol withdrawn rats. Ex vivo or in vivo ethanol exposure and withdrawal causes a long‐lasting increase in NR2B subunit‐containing NMDA receptor activity in the DMS, contributing to ethanol drinking. Analyses of neuronal activation associated with alcohol withdrawal and site‐directed lesions in mice implicate the rostroventral caudate putamen, a ventrolateral segment of the DMS, in genetically determined differences in risk for alcohol withdrawal involved in physical association of the multi‐PDZ domain protein, MPDZ, with 5‐HT_2C receptors and/or NR2B. Conclusions: Alterations of dopaminergic, glutamatergic, and GABAergic signaling within different regions of the striatum by alcohol is critical for alcohol craving, consumption, dependence, and withdrawal in humans and animal models.     

Prazosin effects on stress- and cue-induced craving and stress response in alcohol-dependent individuals: preliminary findings

Background: Stress, alcohol cues, and dysregulated stress responses increase alcohol craving and relapse susceptibility, but few pharmacologic agents are known to decrease stress‐ and cue‐induced alcohol craving and associated stress dysregulation in humans. Here we report findings from a preliminary efficacy study of the alpha‐1 receptor antagonist, prazosin, in modulating these relapse‐relevant factors in alcohol‐dependent individuals. Methods: Seventeen early abstinent, treatment‐seeking alcohol‐dependent individuals (12 men and 5 women) were randomly assigned to receive either placebo or 16 mg daily prazosin in a double‐blind, placebo‐controlled manner over 4 weeks. During week 4, all patients participated in a 3‐day laboratory experiment involving 5‐minute guided imagery exposure to stress, alcohol cue, and neutral‐relaxing/control conditions, 1 exposure per day, on consecutive days in a random, counterbalanced order. Alcohol craving, anxiety, negative emotion, cardiovascular measures, and plasma hypothalamic–pituitary–adrenal (HPA; cortisol, adenocorticotropic hormone) were assessed repeatedly in each session. Results: The prazosin group (n = 9) versus the placebo group (n = 8) showed significantly lower alcohol craving, anxiety, and negative emotion following stress exposure. The placebo group also showed significantly increased stress‐ and cue‐induced alcohol craving, anxiety, negative emotion, and blood pressure (BP), as well as a blunted HPA response relative to the neutral condition, while the prazosin group showed no such increases in craving, anxiety, negative emotion, and BP, and no blunted HPA response to stress and alcohol cue exposure. Conclusions: Prazosin appears efficacious in decreasing stress‐ and cue‐induced alcohol craving and may normalize the stress dysregulation associated with early recovery from alcoholism. Further research to assess the efficacy of prazosin in reducing alcohol craving and stress‐related relapse risk is warranted.     

Sensation Seeking in Long‐Term Abstinent Alcoholics,Treatment‐Naïve Active Alcoholics,and Nonalcoholic Controls

Background: Elevated sensation seeking is associated with the development of alcohol dependence; however, it has not been studied in long‐term abstinent alcoholics. In the current study, we examine sensation seeking in middle‐aged long‐term abstinent alcoholics (LTAA) and in younger actively drinking treatment‐naïve alcoholics (TxN). Methods: A modified version of the Sensation Seeking Scale (SSS) was administered to 52 middle‐aged LTAA (average age = 46.6 years) and 86 younger TxN (average age = 31.2 years), each study with its own age and gender comparable nonalcoholic controls (NAC). The SSS was modified to remove items specifically associated with alcohol or drug use. The associations between the SSS and alcohol use and deviance proneness were examined. Results: The 2 NAC samples did not differ on the SSS, allowing the 2 NAC samples to be combined into a single control group (NAC = 118), and the LTAA and TxN samples to be directly compared without concern for cohort effects. LTAA did not differ from NAC on the SSS; however, the TxN group had higher SSS scores compared with NAC on all subscales except Boredom Susceptibility. Sensation seeking was comparably associated with lower socialization in each group. Conclusions: The results suggest that either sensation seeking normalizes with long‐term abstinence or that relatively normal levels of sensation seeking predict the ability to achieve long‐term abstinence. In either case, the results have important implications for our understanding of long‐term abstinence.     

Increased White Matter Signal Hyperintensities in Long-Term Abstinent Alcoholics Compared with Nonalcoholic Controls

Background: The harmful effects of alcohol dependence on brain structure and function have been well documented, with many resolving with sufficient abstinence. White matter signal hyperintensities (WMSH) are thought to most likely be consequences secondary to the vascular (i.e., hypertension and atherosclerosis) effects of AD. We hypothesized that such effects would persist into long‐term abstinence, and evaluated them in middle‐aged long‐term abstinent alcoholics (LTAA) compared with age and gender comparable nonalcoholic controls (NAC). Methods: Ninety‐seven participants (51 LTAA and 46 NAC) underwent cognitive, psychiatric, and structural brain magnetic resonance image evaluations. WMSH were identified and labeled as deep or periventricular by an automated algorithm developed in‐house. WMSH volumes were compared between groups, and the associations of WMSH measures with demographic, alcohol use, psychiatric, and cognitive measures were examined within group. Results: Long‐term abstinent alcoholics had more WMSH than NAC. There was a significant group by age interaction, with WMSH increasing with age in LTAA, but not in NAC. Within LTAA, WMSH load was independently positively associated with alcohol burden and with age. No associations were evident between WMSH volumes and abstinence duration, family drinking history, years of education, or psychiatric or cognitive variables. Conclusion: The magnitude of alcohol abuse was related to increased WMSH volume. The presence of an age effect in the LTAA but not the controls indicates a synergistic effect wherein alcohol advances the onset of aging‐related WMSH formation. The increased WMSH load did not appear to have any significant clinical correlates, indicating that the white matter lesions in our sample may not have been severe enough to manifest as cognitive deficits. A limitation of the study is that we did not have data on the presence or severity of lifetime or current indices of vascular risk factors such as hypertension, smoking, or diabetes.     

Anxiety and depression among abstainers and low-level alcohol consumers. The Nord-Trøndelag Health Study

Aims The aim of this study was to examine the levels of anxiety and depression among individuals consuming low levels of alcohol. Design Prospective and cross‐sectional population‐based study. Setting and participants This study employed data from the Nord‐Trøndelag Health Survey (HUNT‐2, n = 38 930). Measurements Alcohol consumption was measured by self‐report of usual alcohol consumption during a 2‐week period. Low‐level alcohol consumption was defined as self‐reported abstainers and non‐abstainers currently consuming no alcohol. Anxiety and depression were measured using the Hospital Anxiety and Depression Rating Scale. Potential explanatory variables included somatic illness and symptoms, health‐related behaviour, socio‐economic status and social activity. In a subsample (n = 20 337), we also looked at the impact of previous heavy drinking among abstainers ('sick‐quitting'). Findings A U‐shaped association between alcohol consumption and the risk of anxiety and depression was found. Abstention was related to increased odds for both case‐level anxiety [1.34, 95% confidence interval (CI) 1.19–1.52] and depression (1.52, 95% CI 1.30–1.77). This association was accounted for partly by adjustments for socio‐economic status, social network, somatic illness, age (depression only), gender (anxiety only) and ‘sick‐quitting’. We also identified significant differences between participants who label themselves as abstainers compared to those who report no usual alcohol consumption, but who do not label themselves as abstainers. Conclusions The risk of case‐level anxiety and depression is elevated in individuals with low alcohol consumption compared to those with moderate consumption. Individuals who label themselves as abstainers are at particularly increased risk. This increased risk cannot fully be explained by somatic illness, social activity or ‘sick‐quitting’.