Assessment of the role of kindling in the pathogenesis of alcohol withdrawal seizures and delirium tremens

The aim of this study was to evaluate the hypothetical role of kindling phenomenon in the development and course of alcohol withdrawal (AW) seizures and delirium tremens (DT). The 2186 medical records of 1179 patients hospitalized in Nowowiejski Hospital in Warsaw from 1973 to 1987 were reviewed using a structured questionnaire. Investigating the role of kindling, a course of consecutive AW episodes of patients hospitalized several times was analyzed. The relationships of withdrawal seizures with the duration of alcohol abuse, the number of prior detoxification episodes, and other variables were also studied. Increasing severity of AW symptoms was observed during the course of consecutive episodes in 22.5% of patients. The first episode of DT was preceded by withdrawal seizures in 11% of cases. First-ever withdrawal seizures occurred more frequently in patients with head injury in the past and with coexisting symptoms of alcohol liver disease. Occurrence of withdrawal seizures and DTs did not correlate with the number of previous withdrawal episodes or with the length of period of intensive drinking. We concluded that the kindling model could be applied only to some cases in the development of AW seizures and DTs. Kindling should be considered as one of the multiple mechanisms involved in the pathogenesis of AW delirium.     

Glucose metabolism, insulin-like growth factor-I, and insulin-like growth factor-binding protein-1 after alcohol withdrawal

Alcohol abusers often present with deteriorated glucose metabolism and insulin resistance. Changes in other glucoregulators, such as insulin-like growth factor-I (IGF-I) and IGF-binding protein-1 (IGFBP-1) may also be related to alcohol abuse. We studied the effects of alcohol withdrawal on blood glucose, serum insulin and C-peptide, and plasma IGF-I and IGFBP-1 levels in 27 noncirrhotic male alcoholics aged 43 +/- 9.0 (mean +/- SD) years on four consecutive days immediately after withdrawal. A 4-day monitoring period was conducted in four healthy nonalcoholic control men. The groups were similar in age and body mass index. Glucose, insulin, IGF-I, and IGFBP-1 did not differ significantly between the groups at the baseline, but C-peptide was higher in alcoholics (p < 0.01). After alcohol withdrawal, serum insulin and C-peptide levels increased in close correlation with each other (r = 0.82, p < 0.001). During the 4-day observation period in alcoholics, IGFBP-1 levels declined by 59%, whereas IGF-I increased by 41% (p < 0.001 for both comparisons). The change in insulin correlated inversely with the change in IGFBP-1 levels (r = -0.39, p < 0.05). In the control group, glucose, insulin, IGF-I, and IGFBP-1 remained unchanged during the 4-day monitoring period, whereas some reduction was observed in C-peptide. In conclusion, alcohol withdrawal enhances insulin production, as seen in increased C-peptide levels. An inverse correlation between the changes in insulin and that in IGFBP-1 might suggest that inhibition of IGFBP-1 by insulin remains largely unchanged during the acute phase of alcohol withdrawal.     

Alcohol Biomarkers in Patients Admitted for Trauma

Background:  To assess the value of blood alcohol levels (BAL) and carbohydrate-deficient transferrin (CDT) in trauma patients.
Methods:  A prospective study was conducted among 213 patients admitted to a university hospital after trauma. Outcomes of interest included the development of alcohol withdrawal, infections, respiratory problems, cardiac events, thromboembolism, and length of stay.
Results:  The majority (78%) of the trauma patients in the study was males over the age of 18. Seventy-five percent were reported drinking an alcohol-containing beverage in the previous 30 days, 34% had ≥5 heavy drinking days, and 18.7% met current DSM-IV criteria for alcohol abuse and 13.1% current criteria for dependence. Twenty-two percent ( n  = 48) had a positive BAL and 14% ( n  = 30) a CDT level > 2.5%. Twelve percent ( n  = 27) of the sample developed alcohol withdrawal and 55% ( n  = 113) had one or more adverse health events during their hospitalization. The development of alcohol withdrawal was associated with an admission CDT >2.5% (χ²: 4.77, p  < 0.029) and/or a positive BAL (χ²: 54.01, p  < 0.001). The alcohol biomarkers identified 13 male and 3 female high-risk patients (7.4% of the total sample) who denied excessive alcohol use, and who would have been missed if these markers were not used. A composite morbidity trauma score composed of 25 adverse health events was associated with a positive BAL ( p  < 0.022).
Conclusion:  The study provides additional empirical evidence that supports the use of BAL in all patients admitted for trauma. The usefulness of CDT in trauma patients remains unclear and will require larger samples in more critically ill patients.     

Validity of self-reported alcohol consumption in nondependent drinkers with unintentional injuries

BACKGROUND: Self-report has become an anchor for alcohol assessment in the acute and primary care populations. The purpose of the study was to determine the validity of self-reported alcohol consumption after unintentional injuries in hospitalized, nondependent drinkers. METHODS: Non-alcohol-dependent subjects 18 years of age and older with unintentional injuries (n = 209) were enrolled in the study and were interviewed if they had either an admitting blood alcohol concentration (BAC) > or = 10 mg/dl (0.01 g/dl) or a positive screen for a history of problem drinking. The self-reported number of standard drinks, time that drinking commenced, sex, and weight were used to calculate estimated blood alcohol concentration (EBAC), which was then compared to the admission BAC. RESULTS: We had data to calculate the EBAC on 141 of the 209 subjects. Seven men and no women with positive (> or = 10 mg/dl) BAC denied drinking. Of the 134 subjects for whom we had data to calculate EBAC and who acknowledged drinking, mean BAC was 147.06 mg/dl and mean EBAC was 68.66 mg/dl. For women (n = 30), mean BAC was 149.53 mg/dl and mean EBAC was 114.67 mg/dl; for men (n = 104), mean BAC was 146.35 mg/dl and mean EBAC was 55.38 mg/dl. The Spearman's p between laboratory BAC and EBAC was 0.461 (p < 0.001) for all subjects (n = 134), 0.275 (NS) for women (n = 30), and 0.532 (p < 0.001) for men (n = 104). For women and men separately, multiple regression analyses were performed to predict BAC by using weight and reported number of drinks. For women, weight and number of drinks accounted for 3% of the variance in laboratory BAC [r = 0.181, F(2,47) = 0.797,p = NS]. In contrast, for men these same predictors accounted for 34% of the variance [r = 0.585, F(2,135) = 35.203,p < 0.001). CONCLUSIONS: Most nondependent patients with unintentional injury acknowledged drinking before injury. After injury, women and men have different patterns of reporting their drinking, with men more frequently underreporting but reporting more accurately and women more random in their self-reports.     

Does Carbohydrate-Deficient Transferrin Predict the Severity of Alcohol Withdrawal Syndrome?

Alcohol withdrawal often causes severe complications. However, many addicts deny any abuse. Thus, the diagnosis of alcohol abuse frequently becomes difficult. Laboratory parameters are often used to support the diagnosis of alcohol abuse. Furthermore, laboratory parameters should facilitate the prediction of the severity of alcohol withdrawal syndrome (AWS). The most promising laboratory parameter indicating a recent elevated alcohol consumption is carbohydrate-deficient transferrin (CDT). The aim of this study was to examine whether the measurement of CDT at admission can indicate a higher risk for the development of a complicated AWS. The severity of AWS was assessed by the AWS scale, consisting of two subscales for somatic and mental symptoms. CDT was measured by different methods (radioimmunoassay and HPLC). The radioimmunoassay for CDT (CDTect) yielded the best prediction. Our results showed a weak correlation between CDTect and the severity of AWS. However, there were great gender differences. In men, CDTect had the highest positive predictive value for a severe AWS (86.7%), whereas in women mean corpuscular volume was the best predictor (77.8%). However, the sensitivity of CDTect in men (25.5%), as well as mean corpuscular volume in females (29.2%), was too low for a screening test in a general hospital.     

Alcohol abuse in a metropolitan city in China: a study of the prevalence and risk factors

AIMS: To investigate the prevalence of alcohol abuse in modern China and to explore the risk factors that may be associated with alcohol abuse. DESIGN: A face-to-face interview was carried out in a random sample with 2327 respondents. SETTING: Respondents were selected randomly from Wuhan City, Hubei Province, China, between May and June 2002. Participants Fifteen-65-year-old urban Chinese adults. MEASUREMENTS: Scores for alcohol abuse and related risk factors were the main measures. FINDINGS: (1) Nearly 15% of urban Chinese adults aged 15-65 were alcohol abusers. (2) Deviant drinking habits of mother, schoolmates, colleagues or friends all had a negative impact on the respondent's alcohol drinking behaviours, and higher economic status, current smokers, being male and being older were identified as risk factors related to alcohol abuse. In particular, if a drinker's mother used alcohol frequently then this drinker was more likely to become an alcohol abuser than those drinkers whose mothers did not use alcohol frequently (P = 0.0001). Fathers' drinking behaviours do not have a significant impact on the alcohol abusers. CONCLUSIONS: In addition to common risk factors such as economic status, deviant peers' and fellows' drinking behaviours and negative attitudes to alcohol drinking, maternal alcohol drinking habit influenced significantly the offspring's drinking habits. Therefore, efficient intervention and education of healthy drinking habits in early motherhood is necessary for Chinese women.     

The role of somatic disorders and physical injury in the development and course of alcohol withdrawal delirium

In a retrospective study, we evaluated the role of somatic disease and physical injury in the development and course of alcohol withdrawal delirium. Medical records of 1179 patients treated for alcohol withdrawal in Nowowiejski Hospital in Warsaw from 1973 to 1987 were reviewed using a structured questionnaire. Development, symptoms' severity, and the course of alcohol withdrawal delirium were assessed in possible relation to the somatic state of patients and other variables of alcohol dependence. Development of the first episode of delirium tremens (DT) was associated with the incidence of somatic disease or injury in 19% of cases. Somatic disorders directly preceded the second episode of DT in 73% and the third in 57% of cases. A positive correlation was found between the greater severity and/or longer duration of DT symptoms, and occurrence of pneumonia, coronary heart disease, alcohol liver disease, and anemia, as well as daily amount of alcohol consumed during the last drinking bout. There was no relationship of severity of DT with the duration of alcohol abuse. Early development and severe course of alcohol withdrawal delirium correlated with the late beginning of excessive drinking (over the age of 40) and concomitant abuse of benzodiazepines or barbiturates. We concluded that somatic disorders or physical injury might trigger delirium during alcohol withdrawal, and have essential influence on the symptoms' severity and duration of DT. A more severe course of DT is also correlated with the quantity of alcohol consumed and concomitant abuse of sedatives.     

Bone mineral density and abstention-induced changes in bone and mineral metabolism in noncirrhotic male alcoholics.

BACKGROUND AND PURPOSE: Abuse of alcohol may derange bone metabolism and cause osteoporosis. Due to confounding factors associated with alcohol abuse, however, the effect of alcohol itself on bone loss remains obscure. The influence of alcohol intake on bone and mineral metabolism is rather well known, but how the metabolism normalizes during withdrawal has rarely been investigated. The aims of the present study were to evaluate the alcohol-induced changes of bone and mineral metabolism and their recovery during abstention, and to reassess any possible link between alcohol abuse and osteoporosis. PATIENTS AND METHODS: We studied 27 non-cirrhotic male alcoholics hospitalized for 2 weeks for withdrawal. For comparison, three groups of control subjects were examined. Serum and urinary parameters of bone and mineral metabolism as well as intestinal absorption of calcium were determined at the beginning and end of the treatment period. Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry at four axial sites (lumbar spine, femoral neck, Ward's triangle, trochanter). RESULTS: On admission, bone formation in the alcoholics was reduced as reflected by decreased serum levels of osteocalcin (-28%; p < 0.05) and procollagen I carboxyterminal propeptide (-17%; p < 0.05). Both parameters normalized within 2 weeks of abstention (p < 0.0001 and p < 0.01, respectively). Urinary hydroxyproline, a parameter of bone resorption, was at the control level on admission and increased slightly during abstention (p < 0.05). Serum ionized calcium increased by 3% (p < 0.0001) during withdrawal. Concomitantly, serum free fatty acids (FFA) decreased by 38% (p < 0.001), and there existed an inverse correlation (r = -0.50, p < 0.05) between changes in ionized calcium and FFA. Serum levels of intact parathyroid hormone and vitamin D metabolites were similar in patients and controls throughout the whole observation period. Intestinal absorption of calcium measured by stable strontium was 37% higher in alcoholics than in controls (p < 0.001); it decreased to nearly normal toward the end of the treatment period. Mean axial BMD did not differ between patients and controls at any of the four measurement sites. However, BMD decreased parallel with duration of drinking history in the alcoholics at all axial sites (p < 0.05 to < 0.01, analysis of covariance with age and weight as covariates). CONCLUSIONS: Decreased bone formation, which is uncoupled from ongoing bone resorption, recovers completely during 2 weeks of abstention. In the absence of confounding factors, the central BMD is normal in noncirrhotic male alcoholics, although the negative effect of alcohol on BMD is evident when duration of excessive drinking is taken into account.     

The relationship between recent alcohol use and sexual behaviors: gender differences among sexually transmitted disease clinic patients

Background: Binge drinking is associated with risky sexual behaviors and sexually transmitted diseases (STDs). Few studies have investigated this by gender or in an STD clinic. This cross‐sectional study examined the association between binge drinking and risky sexual behaviors/STDs among patients attending an urban STD clinic. Method: A total of 671 STD clinic patients were tested for STDs, and queried about recent alcohol/drug use and risky sexual behaviors using audio computer‐assisted‐self‐interview. The association between binge drinking and sexual behaviors/STDs was analyzed using logistic regression adjusting for age, employment, and drug use. Results: Binge drinking was reported by 30% of women and 42% of men. Gender differences were found in rates of receptive anal sex which increased linearly with increased alcohol use among women but did not differ among men. Within gender analyses showed that women binge drinkers engaged in anal sex at more than twice the rate of women who drank alcohol without binges (33.3% vs. 15.9%; p < 0.05) and 3 times the rate of women who abstained from alcohol (11.1%; p < 0.05). Having multiple sex partners was more than twice as common among women binge drinkers than women abstainers (40.5% vs. 16.8%; p < 0.05). Gonorrhea was nearly 5 times higher among women binge drinkers compared to women abstainers (10.6% vs. 2.2%; p < 0.05). The association between binge drinking and sexual behaviors/gonorrhea remained after controlling for drug use. Among men, rates of risky sexual behaviors/STDs were high, but did not differ by alcohol use. Conclusion: Rates of binge drinking among STD clinic patients were high. Among women, binge drinking was uniquely associated with risky sexual behaviors and an STD diagnosis. Our findings support the need to routinely screen for binge drinking as part of clinical care in STD clinics. Women binge drinkers, in particular, may benefit from interventions that jointly address binge drinking and risky sexual behaviors. Developing gender‐specific interventions could improve overall health outcomes in this population.     

Effects of acamprosate on sleep during alcohol withdrawal: A double-blind placebo-controlled polysomnographic study in alcohol-dependent subjects

BACKGROUND: Sleep disturbances are frequently encountered in alcohol-dependent patients. Drugs improving sleep during abstinence from alcohol may play an important role in the recovery process. METHODS: In the present study, the effects of acamprosate, a drug successfully used in maintaining abstinence following alcohol withdrawal, were assessed by polysomnographic recordings. A parallel double-blind placebo-controlled study was conducted in 24 male DSM-IV alcohol-dependent subjects aged 35.9+/-1.2 years. Treatments (2 tablets of 333 mg acamprosate vs placebo t.i.d.) were initiated 8 days before alcohol withdrawal and continued during the 15 days following alcohol withdrawal. Polysomnographic assessments were recorded during acute withdrawal (the first 2 nights following withdrawal) and during postwithdrawal abstinence (the last 2 nights of the trial). RESULTS: Results show that, compared with placebo, acamprosate decreased wake time after sleep onset and increased stage 3 and REM sleep latency (all treatment effects with a p < 0.05 significance). Withdrawal effects themselves were also demonstrated as sleep efficiency (p < 0.01) and total sleep time (p < 0.05) were lower in abstinence nights versus withdrawal nights, whereas no significant treatment x withdrawal effect could be evidenced. Acamprosate was well tolerated during the entire course of the study. CONCLUSIONS: The present study shows that acamprosate ameliorates both sleep continuity and sleep architecture parameters classically described as disturbed in alcohol-dependent patients. From a clinical perspective, it suggests that an 8-day acamprosate prewithdrawal treatment is well tolerated and can attenuate the sleep disturbances engendered by alcohol withdrawal in alcohol-dependent subjects.     

A Double-Blind Trial of Gabapentin Versus Lorazepam in the Treatment of Alcohol Withdrawal

Introduction: Some anticonvulsants ameliorate signs and symptoms of alcohol withdrawal, but have an unacceptable side effect burden. Among the advantages of using anticonvulsant agents in this capacity is their purported lack of interaction with alcohol that could increase psychomotor deficits, increase cognitive impairment, or increase intoxication. The aim of this study was to evaluate alcohol use and symptom reduction of gabapentin when compared with lorazepam in the treatment of alcohol withdrawal in a double‐blinded randomized clinical trial. Methods: One hundred individuals seeking outpatient treatment of alcohol withdrawal with Clinical Institute Withdrawal Assessment for Alcohol–Revised (CIWA‐Ar) ratings ≥10 were randomized to double‐blind treatment with 2 doses of gabapentin (900 mg tapering to 600 mg or 1200 tapering to 800 mg) or lorazepam (6 mg tapering to 4 mg) for 4 days. Severity of alcohol withdrawal was measured by the CIWA‐Ar on days 1 to 4 of treatment and on days 5, 7, and 12 post‐treatment and alcohol use monitored by verbal report and breath alcohol levels. Results: CIWA‐Ar scores decreased over time in all groups; high‐dose gabapentin was statistically superior but clinically similar to lorazepam (p = 0.009). During treatment, lorazepam‐treated participants had higher probabilities of drinking on the first day of dose decrease (day 2) and the second day off medication (day 6) compared to gabapentin‐treated participants (p = 0.0002). Post‐treatment, gabapentin‐treated participants had less probability of drinking during the follow‐up post‐treatment period (p = 0.2 for 900 mg and p = 0.3 for 1200 mg) compared to the lorazepam‐treated participants (p = 0.55). The gabapentin groups also had less craving, anxiety, and sedation compared to lorazepam. Conclusions: Gabapentin was well tolerated and effectively diminished the symptoms of alcohol withdrawal in our population especially at the higher target dose (1200 mg) used in this study. Gabapentin reduced the probability of drinking during alcohol withdrawal and in the immediate postwithdrawal week compared to lorazepam.     

Association of alcohol dehydrogenase genes with alcohol-related phenotypes in a Native American community sample

Background: Previous linkage studies, including a study of the Native American population described in the present report, have provided evidence for linkage of alcohol dependence and related traits to chromosome 4q near a cluster of alcohol dehydrogenase (ADH) genes, which encode enzymes of alcohol metabolism. Methods: The present study tested for associations between alcohol dependence and related traits and 22 single‐nucleotide polymorphisms (SNPs) spanning the 7 ADH genes. Participants included 586 adult men and women recruited from 8 contiguous Native American reservations. A structured interview was used to assess DSM‐III‐R alcohol dependence criteria as well as a set of severe alcohol misuse symptoms and alcohol withdrawal symptoms. Results: No evidence for association with the alcohol dependence diagnosis was observed, but an SNP in exon 9 of ADH1B (rs2066702; ADH1B*3) and an SNP at the 5′ end of ADH4 (rs3762894) showed significant evidence of association with the presence of withdrawal symptoms (p = 0.0018 and 0.0012, respectively). Further, a haplotype analysis of these 2 SNPs suggested that the haplotypes containing either of the minor alleles were protective against alcohol withdrawal relative to the ancestral haplotype (p = 0.000006). Conclusions: These results suggest that variants in the ADH1B and ADH4 genes may be protective against the development of some symptoms associated with alcohol dependence.     

Disparities in Alcohol Treatment Utilization by Race and Type of Insurance

Even though women are more likely to develop alcohol problems when drinking equivalent amounts as men, transition from regular drinking to intoxication within a shorter period of time, and develop serious problems faster, men are more likely to utilize alcohol treatment. Furthermore, little is known about factors contributing to treatment utilization by women. Data from the National Epidemiologic Survey on Alcohol and Related Conditions, Wave 1, were examined to determine what predicted alcohol treatment utilization among women. Contrary to our hypothesis, having no insurance benefits predicted greater odds of utilizing alcohol treatment compared to having private insurance. Furthermore, the only diagnosis of alcohol-use problems that predicted treatment utilization was concurrent alcohol abuse and dependence. Criteria for alcohol abuse only or dependence only did not predict whether women sought alcohol treatment.     

The relationship between educational attainment and relapse among alcohol-dependent men and women: a prospective study

BACKGROUND: We investigated the relationship between educational attainment and drinking outcomes after discharge from inpatient treatment for alcohol dependence. METHODS: Between 1993 and 1996, we consecutively recruited 41 women and 60 men hospitalized for alcohol dependence and followed them up monthly for 1 year. We conducted structured interviews during hospitalization and at monthly intervals after discharge for 1 year. We examined the relationship between educational attainment before treatment and postdischarge drinking outcomes, including time to relapse. RESULTS: After covariate adjustment, educational level was a significant predictor of drinking outcomes. CONCLUSIONS: Lower levels of educational attainment before entry into treatment predicted shorter times to first drink and relapse in both women and men. The association of educational attainment and treatment outcome for alcohol dependence warrants further investigation.     

Increased Susceptibility to Liver Disease in Relation to Alcohol Consumption in Women

Sex-related differences were prospectively studied in patients with the first presentation of alcoholic liver disease. Among 42 patients the diagnosis was cirrhosis in 8 women and 15 men, alcoholic hepatitis in 4 women and 1 man, steatosis in 6 women and 6 men, and no histologic changes were found in the liver biopsy specimens from 2 men (p > 0.1). The median (range) antipyrine clearance was 14.6 (1.0–64) versus 17.2 (3.0–83) ml/min and the clinical score in accordance with the Pugh modification of the Child-Turcotte classification was 8 (5–13) versus 8 (5–11) in the women and men, respectively (p > 0.05). In 5 women and only 1 man the antipyrine clearance was less than 5 ml/min, indicating an almost total loss of functional liver mass (p < 0.05), whereas the Pugh score was above 11 in 6 women, but not in any of the men (p < 0.05). On an average, the men estimated their total lifetime consumption of alcohol to be 2.1 times greater and the number of days they had consumed more than 5 drinks 2.9 times higher than the women (p < 0.05). These ratios are reduced to 1.4 and 1.7, respectively (p > 0.05), if the female alcohol intake is adjusted to the average male volume of distribution. The results support the concept that women may develop similar, and sometimes even more severe, liver disease after consumption of less alcohol than men. The apparent difference in susceptibility to alcohol may be partly explained by differences in volume of distribution.     

Naltrexone Increases the Latency to Drink Alcohol in Social Drinkers

We investigated the effects of naltrexone (NTX) on alcohol drinking, urge to drink alcohol, and alcohol-induced sensations and mood states in social drinkers consuming alcohol ad libitum in a cocktail bar. Sixteen college-age men and women participated in a double-blind, placebo-controlled, within-subjects, cross-over study. Subjects were tested during each of three drug conditions: NTX, 50 mg/day, po; inactive placebo; and no drug. Each treatment condition lasted 8 to 11 days. Small groups of subjects consumed alcohol ad libitum during three 2-hr evening drinking sessions, separated by ˜2 weeks. NTX treatment significantly increased the latency (time in seconds) to first sip the first ( p < 0.05) and second alcoholic beverages consumed ( p < 0.01). Moreover, the mean blood alcohol concentration at the end of the session was significantly lower when subjects were treated with NTX ( p < 0.05). No differences were found on self-report urge to drink alcohol. Subjects reported more fatigue and tension on the Profile of Mood States ( p < 0.05), before drinking, and increases in nausea on the Alcohol Sensation Scale ( p < 0.05) when treated with NTX. The increase in the latency to sip the first and second alcoholic beverages may reflect the capacity of NTX to block urge for alcohol elicited from external cues (before consuming alcohol), as well as urge for alcohol after priming from ingested alcohol. Thus, the effectiveness of NTX for reducing drinking behaviors of alcoholics may be partially caused by anticraving properties of NTX.     

Acoustic startle reactivity during acute alcohol withdrawal in rats that differ in genetic predisposition toward alcohol drinking: effect of stimulus characteristics

BACKGROUND: We have previously reported an association between greater alcohol withdrawal magnitude after a single alcohol exposure and a genetic predisposition toward low alcohol drinking in rats selectively bred for differences in alcohol intake when acoustic startle reactivity to a tone stimulus was used to index acute alcohol withdrawal. The purpose of this study was to examine whether the quality of the acoustic startle stimulus (noise versus tone) is important for detecting a genetic relationship between alcohol withdrawal magnitude and alcohol drinking behavior. METHODS: Alcohol-naive male rats selectively bred for high alcohol intake [alcohol-preferring (P), high-alcohol-drinking (HAD)1, and HAD2] or low alcohol intake [alcohol-nonpreferring (NP), low-alcohol-drinking (LAD)1, and LAD2] received a single intragastric infusion of water or alcohol (4.0 g/20.3 ml/kg; 25% v/v), and acoustic startle test sessions were given at 14, 16, 18, 20, and 24 hr after infusion. Each test session consisted of a 5-min acclimation period followed by random presentation of various white noise stimuli (90, 100, 110, and 120 dB.) RESULTS: Line differences in acoustic startle magnitude under control conditions were present in all three pairs of selectively bred lines; P rats showed a greater startle magnitude relative to NP rats, whereas both LAD lines showed a greater startle magnitude relative to both HAD lines. During alcohol withdrawal, the P, HAD1, and HAD2 lines showed enhanced startle magnitude compared with their water-treated controls. No change in startle magnitude during alcohol withdrawal was found in the NP, LAD1, or LAD2 lines. CONCLUSIONS: In contrast to our prior findings, these results showed a genetic association between high alcohol drinking and a greater startle response magnitude to a noise stimulus during alcohol withdrawal. It seems that the genetic association between alcohol drinking and alcohol withdrawal, as assessed by the acoustic startle response, depends on the quality of the acoustic startle stimulus.     

Cardiovascular responses to physical and psychological stress in female alcoholics with transitory hypertension after early abstinence

BACKGROUND: Male alcoholic patients with acute withdrawal hypertension have shown exaggerated cardiovascular reactivity to stress after 3 to 4 weeks of abstinence, although resting blood pressures (BP) had returned to normal. Studies of this nature, however, have not been extended to women. METHODS: In this study, 32 alcohol-dependent women, abstinent for 4 weeks, were compared with 16 healthy controls on cardiovascular hemodynamics during rest and in response to 2 moderately aversive stressors: isometric handgrip and a speech task. The alcoholics were placed according to withdrawal BP into transitory hypertensive (tHT; n = 16; BP >or=140/90 mm Hg) and normotensive (NT; n = 16; BP <140/90 mm Hg) subgroups. RESULTS: During stress testing, the transitory hypertensive women had increased diastolic BP (p < 0.01), a higher peripheral resistance index (p < 0.05), and a reduced cardiac efficiency index (p < 0.03) relative to the normotensive and control subjects. CONCLUSIONS: This cardiovascular pattern suggests that both cardiac and vascular functions were altered adversely in the transitory hypertensives. In contrast to men examined in previous studies, the transitory hypertensive women had no exaggeration of BP reactivity, but instead showed sustained alterations of resting cardiovascular function in relation to chronic alcohol consumption. Although the pattern of cardiovascular dysregulation seems to be different in female alcoholics than in males, it is consistent with studies showing that cardiovascular effects in women are more severe than in men and emerge at a lower threshold level of chronic drinking.     

Neurochemical Correlates of Sympathetic Activation during Severe Alcohol Withdrawal

Cerebrospinal fluid (CSF) was obtained from 17 patients during acute alcohol withdrawal. Eight of these 17 patients had a second lumbar puncture a mean of 11.9 ± 8.1 ( sd ) days later, when the clinical signs of alcohol withdrawal had subsided. CSF 3-methoxy-4-hydroxyphen-ylglycol concentrations declined significantly ( p < 0.05) during the course of alcohol withdrawal from 52.0 ± 22.1 ( sd ) to 39.6 ± 12.6 pM/ml. In early withdrawal, there was a significant positive correlation between CSF norepinephrine (NE) and corticotropin releasing hormone (CRH) concentrations ( r = 0.95, p <0.001). Both NE and CRH concentrations correlated positively with diastolic blood pressure ( r = 0.88, p < 0.001 and r = 0.62, p < 0.05, respectively). In all samples, CSF 5-hydroxyindole acetic acid concentrations correlated positively with CSF-homovanillic acid concentrations ( r = 0.83, p < 0.001). These findings indicate significant perturbations of the noradrenergic neuronal system and a change in CRH-NE interactions during acute alcohol withdrawal.     

Dose-Related Impact of Alcohol Consumption on Cognitive Function in Advanced Age: Results of a Multicenter Survey

BACKGROUND: Moderate alcohol consumption has been associated in several studies with decreased risk of cardiovascular and cerebrovascular events; however, available data on the effects of alcohol intake on cognitive functioning are conflicting. We assessed the association between alcohol consumption and cognitive impairment in a series of older subjects enrolled in a multicenter pharmacoepidemiology survey. METHODS: The association between average alcoholic intake and cognitive performance was assessed in 15,807 patients admitted to participating centers during the survey periods. Demographic variables, comorbid conditions, medications, and objective tests that were associated with cognitive impairment (as indicated by a Hodkinson Abbreviated Mental Test score <7) in separate logistical regression models were examined as potential confounders in a summary model. RESULTS: Cognitive impairment was detected in 1693 (19%) of 8755 drinkers and 2008 (29%) of 7052 nondrinkers (Fisher's exact test, p < 0.0001). After adjusting for potential confounders, alcohol consumption was associated with decreased probability of cognitive impairment (odds ratio, 0.75; 95% confidence interval, 0.66-0.85). The relationship between drinking level and cognitive dysfunction was nonlinear, because the probability of cognitive impairment was decreased for moderate alcohol use as compared with abstinence, but it was increased for daily consumption exceeding one wine-equivalent liter among men and 0.5 liter among women. This nonlinear association persisted when cerebrovascular and Alzheimer's disease were considered separately. CONCLUSIONS: Alcohol abuse is associated with increased prevalence of cognitive dysfunction among older subjects; however, a daily alcohol consumption of less than 40 g for women and 80 g or less for men might be associated with a decreased probability of cognitive impairment. This possible protective effect of alcohol consumption should be further assessed by prospective studies.