Severity of alcohol withdrawal symptoms and the T1128c polymorphism of the neuropeptide Y gene

Summary. Neuropeptide Y (NPY) modulates ethanol drinking in rodents. The C-allele of the T1128C polymorphism of the human NPY gene has been previously associated with elevated alcohol consumption in a Finn population study. The present study tested the hypothesis that the T1128C polymorphism is associated with the diagnosis of alcoholism or with severe forms of alcohol withdrawal and with the daily consumption of alcohol in alcoholic patients. After PCR-RFLP genotyping, two groups of alcoholics with severe withdrawal symptoms (delirium tremens, n = 83; withdrawal seizures, n = 65) were compared to alcoholics with mild withdrawal symptoms (n = 97). An elevated frequency of the C-allele in the individuals with severe withdrawal symptoms was found, however not reaching statistical significance. Further a group of healthy controls (n = 102) was compared to all included alcoholics (n = 216) revealing no significant result. Alcoholics carrying the C-allele reported a non significantly elevated daily consumption of alcohol compared to alcoholics with the TT genotype. All alcohol dependent subjects with severe withdrawal symptoms revealed a significantly elevated daily consumption of alcohol compared to alcoholics with only mild withdrawal symptoms. More studies on different ethnic groups are needed to further elucidate the influence of the NPY gene on alcoholism. Received January 7, 2002; accepted April 17, 2002 Published online June 28, 2002 Acknowledgements This study was financially supported by the “fortuene-fund” (project 490) of Tuebingen University, Germany. We are grateful to all individuals participating in the study. Authors' address: Dr. M. D. Koehnke, University Hospital of Psychiatry, Osianderstrasse 24, D-72076 Tuebingen, Federal Republic of Germany, e-mail: michael.koehnke@med.uni-tuebingen.de     

Norepinephrine transporter gene polymorphism is not associated with susceptibility to alcohol dependence

Abnormalities in monoamine neurotransmission have been implicated in the pathogenesis of alcoholism, mood disorders and schizophrenia. Murine norepinephrine transporter gene (NET) has been mapped to a region on chromosome 8 where a quantitative trait locus for ethanol sensitivity. Therefore we tested whether norepinephrine transporter (NET) gene variants confer susceptibility to either alcohol dependence or severe alcohol withdrawal symptoms. There is a highly polymorphic silent G1287A mutation in the NET gene. In our study 157 alcoholics and 185 healthy unrelated matched control subjects were analyzed for a silent G1287A mutation. No significant differences in allele and genotype distribution between control subjects f(A)=0.33 and alcoholics f(A)=0.29 were found. No significant results were found in more homogenous subgroups, i.e. alcoholics with severe alcohol withdrawal (seizures, delirium), early onset age<26 nor dependent patients with positive familial history of alcoholism. These results suggest that the NET gene polymorphism in exon 9 accession number: mRNA: NM_001043, genomic contig.: NT_019610, is unlikely to be involved in the susceptibility to alcoholism and severe alcohol withdrawal.     

Interhemispheric electroencephalographic coherence as a biological marker in alcoholism

Electroencephalographic coherence scores in 21 teetotaler first-degree relatives of alcoholics, 27 subjects with alcohol dependence and 21 healthy subjects without a family history of alcohol abuse were compared. The relatives had significantly higher coherence scores in the frontal and parietal leads than the alcoholics and in the frontal and centroparietal leads than in the healthy subjects. This might represent a trait marker of resilience in subjects at high risk for the development of alcoholism.     

Response of the HPA-axis to alcohol and stress as a function of alcohol dependence and family history of alcoholism

Dysfunction of the hypothalamic-pituitary-adrenal (HPA)-axis has been observed in chronic alcoholics and in non-alcoholic sons of alcoholic parents, while genetic and environmental factors, such as stress, may play a significant role in the development of alcoholism. The present study was designed to investigate the response of the HPA-axis to alcohol and stress as a function of family history of alcoholism and chronic alcohol abuse. We determined changes in plasma adrenal corticotrophin (ACTH) and cortisol concentrations in response to a placebo or an alcohol (0.50g ethanol/kg body wt) drink and to a stress task performed 30 min following ingestion of either the placebo or the alcohol drink in social and heavy drinkers with [high risk (HR)] and without [low risk (LR)] a family history of alcoholism. Thus, four groups of healthy male individuals, low risk with no alcohol-dependence diagnosis (LRNAD), high risk with no alcohol-dependence diagnosis (HRNAD), low-risk alcohol dependent (LRAD) and high-risk alcohol dependent (HRAD), participated in the four experimental sessions given in random order. Basal plasma ACTH levels of LRNAD participants were higher from those of the other three groups of participants. Basal plasma cortisol levels of HRAD participants were higher from those of LRNAD and HRNAD but not of LRAD participants. The stress-induced increases of plasma ACTH and cortisol concentrations were more pronounced in LRNAD participants. The alcohol drink prevented the stress-induced increases in plasma ACTH and cortisol of all groups of participants. The self-ratings of anxiety were attenuated in LRNAD and LRAD participants in the alcohol only session and in HRNAD and HRAD participants in the alcohol plus stress session. In conclusion, there are differences in the activity of the HPA-axis as a function of family history and alcohol dependence, while the effect of an alcohol drink on the self-rating of anxiety may be influenced by both family history and stress.     

新疆酒依赖男性患者家庭暴力行为的社会人口学及社会文化学特征研究

目的 探讨新疆酒依赖男性患者家庭暴力行为的社会人口学因素及社会文化学因素,以期为心理干预提供指导.方法 使用自行设计的酒依赖患者家庭暴力调查问卷进行访谈.酒依赖患者均来自新疆精神卫生中心戒酒科及新疆自治区人民医院临床心理科,符合〈中国精神障碍分类与诊断标准（第3版）〉（CCMD-3）中酒依赖诊断标准,均为男性,按其有无家庭施暴史分为施暴组（87例）和无施暴组（84例）.结果 酒依赖男性患者中施暴者民族差异有统计学意义（P＜0.05）,其中汉族酒依赖男性患者施行家庭暴力者比例较高;施暴组年龄、总体收入均低于无施暴组;个体职业者、离婚者明显多于无施暴组（P＜0.05）;两组受教育程度差异无统计学意义（P＞0.05）.施暴组中在成长过程中曾经看见或听见父亲打骂家庭成员或在童年期曾被家庭成员打骂者多于无施暴组（P＜0.05）.结论 酒依赖男性患者施暴组家庭关系不良,收入偏低.在成长经历中接触过暴力史的酒依赖男性患者易实施家庭暴力行为.     

Sweet taste preference as a risk factor for alcohol dependence

OBJECTIVE: Previous research has found that alcoholics have a greater preference for sweet solutions than comparison subjects. This study tested the hypothesis that preference for sweet solutions is a marker for alcoholism risk. METHOD: A total of 122 nonalcoholic subjects (59 men) participated. Fifty-eight subjects had a paternal history of alcoholism, and 64 did not. Each subject rated a series of sucrose solutions for intensity of sweetness and degree of preference. RESULTS: Subjects were able to rate accurately the relative intensity of sweetness in the sucrose solutions. Both subjects with and those without a paternal history of alcoholism preferred a 0.42-M sucrose solution, irrespective of gender. CONCLUSIONS: This study failed to support the hypothesis that sweet preference is a marker of alcoholism risk. The sweet preference observed previously among alcoholics may be a consequence of chronic alcohol consumption or other factors associated with heavy drinking.     

Family history and diagnosis of alcohol dependence in cocaine dependence

Genetic research in alcoholism has made major advances in recent decades. Twin, adoption, high-risk, and familial studies have demonstrated an inheritance factor in alcoholism. No studies have demonstrated a genetic or familial disposition to cocaine and marijuana dependence. Two hundred sixty-three inpatients were given a structured psychiatric interview retrospectively (150) and prospectively (113) to obtain a DSM-III-R diagnosis of substance dependence disorders in the probands and of alcohol dependence in family members. Our study reveals a large number of probands with cocaine dependence with a positive family history for alcohol dependence. Approximately 50% of probands with cocaine dependence had at least a first or second degree relative with a diagnosis of alcohol dependence when studied by the family history and study methods. As many as 89% of probands who met DSM-III-R criteria for cocaine dependence qualified for other substance dependence diagnoses. Our study finds a high prevalence of alcohol (68% and 89%) and cannabis dependence (53% and 46%) in patients with cocaine dependence. Furthermore, the age of onset of alcohol and other drug dependence is early for those with cocaine dependence and precedes the onset of cocaine dependence. The diagnoses of other alcohol and drug dependence in cocaine dependence and in family members of probands with cocaine dependence have important implications for etiology, prognosis, and treatment.     

A case-comparison study of executive functions in alcohol-dependent adults with maternal history of alcoholism

IntroductionAs executive dysfunctions frequently accompany alcohol dependence, we suggest that reports of executive dysfunction in alcoholics are actually due, in some case to a maternal history of alcohol misuse (MHA+). A history of maternal alcohol dependence increases the risk for prenatal alcohol exposure to unborn children. These exposures likely contribute to executive dysfunction in adult alcoholics. To assess this problem, we propose a case-comparison study of alcohol-dependent subjects with and without a MHA.MethodsTen alcohol-dependent subjects, with a maternal history of alcoholism (MHA) and paternal history of alcoholism (PHA), were matched with 10 alcohol-dependent people with only a paternal history of alcoholism (PHA). Executive functions (cancellation, Stroop, and trail-making A and B tests) and the presence of a history of three mental disorders (attention deficit hyperactivity disorder, violent behavior while intoxicated, and suicidal behavior) were evaluated in both populations.ResultsAlcohol-dependent subjects with MHA showed a significant alteration in executive functions and significantly more disorders related to these functions than PHA subjects. The major measures of executive functioning deficit are duration on task accomplishment in all tests. Rates of ADHD and suicidality were found to be higher in MHA patients compared to the controls.ConclusionA history of MHA, because of the high risk of PAE (in spite of the potential confounding factors such as environment) must be scrupulously documented when evaluating mental and cognitive disorders in a general population of alcoholics to ensure a better identification of these disorders. It would be helpful to replicate the study with more subjects.     

Behavioral symptoms and psychiatric diagnoses among 162 children in nonalcoholic or alcoholic families

OBJECTIVE: People with alcoholic relatives have high rates of alcohol abuse and dependence as adults, but their patterns of problems earlier in life are less clear. Many studies have not controlled for parental disorders other than alcoholism or for parents' socioeconomic status and general life functioning. The authors' goal was to conduct a study controlling for such factors. METHOD: Personal structured interviews and a behavioral checklist were administered to the parents of 162 children 7 years old or older whose fathers had participated in the 15-year follow-up of 453 sons of alcoholics with no history of antisocial personality disorder and sons of nonalcoholic comparison subjects originally selected from a university population. RESULTS: There was no significant relationship between a family history of alcoholism and childhood diagnoses of conduct, oppositional, or attention deficit disorders or with behavioral checklist summary scores. However, children with alcoholic relatives apparently have a slightly higher risk for drug abuse or dependence than those without alcoholic relatives. CONCLUSIONS: Once familial antisocial disorders and familial socioeconomic status are controlled for, a family history of alcoholism does not appear to relate to childhood externalizing disorders.     

Alcoholic women in fertile age treated at an alcohol clinic

The consumption of alcohol by women in Sweden is strongly increasing, especially in younger individuals. Since the rediscovery of the teratological properties of alcohol most of the studies concerning foetal alcohol damage in man have covered female skid row alcoholics. This investigation describes the medical and social characteristics of a group of women (n = 92) receiving inpatient care for alcoholism compared with an age-matched control group, in relation to obstetrical history. The conditions in the control group were in accord with those of the general population. Social problems and degree of alcoholism were noticeably advanced among the probands. The proband women who gave birth after established regular alcohol consumption were younger, showed more psychiatric complications during the treatment period, had started drinking and developing signs of advanced alcoholism earlier in life compared with probands who gave birth before established regular alcohol consumption. They also exhibited more social disturbances. The social problems caused by the mothers' alcohol abuse are expected to aggravate the biological consequences to their children.     

Types of alcoholics, II. Application of an empirically derived typology to treatment matching.

Data from 79 male alcoholics who were randomly assigned to either coping skills training or interactional group psychotherapy were used to replicate a multidimensional, empirically derived typology and to evaluate the typology's usefulness in matching patients to treatment. Consistent with previous cluster analysis research, indicators of risk for alcoholism, alcohol dependence, drinking history, and psychopathological impairment distinguished alcoholics along two broad dimensions of vulnerability and severity, with one subtype (type B alcoholics) manifesting an earlier onset of problem drinking, more familial alcoholism, greater dependence on alcohol, and more symptoms of antisocial personality than the other subtype (type A alcoholics). Analyses of outcome indicated that type A alcoholics fared better in interactional treatment and more poorly with coping skills training. Conversely, type B alcoholics had better outcomes with the coping skills treatment and worse outcomes with interactional therapy. Differences in treatment response were maintained for 2 years from the beginning of aftercare treatment.     

Seasonal distribution of suicide in alcoholism

OBJECTIVE: To investigate the seasonal distribution of suicide in alcohol dependence and to make a comparison with unnatural death in alcoholism and suicide in other diagnostic groups. METHOD: Multiaxial ratings of all patients admitted to the Department of Psychiatry in Lund enabled the selection of patients with alcohol dependence (n=1312) during 1949-1969. When followed up to 1997 a total of 102 (99 men) alcoholic patients had taken their own life. Reference groups were patients with severe depression and autopsy cases with other diagnoses. RESULTS: The alcoholic patients showed a peak during the second quarter of the year (34%, P < 0.05). Other diagnostic groups of suicide and unnatural death in alcoholism did not show any overrepresentation in the spring. CONCLUSION: Male alcoholics showed a spring peak of suicide as opposed to other diagnostic groups.     

Behavioral and EEG responses to alcohol in nonalcoholic men with a family history of alcoholism

1. 1. Behavioral and EEG responses were examined in nonalcoholic males with (FH+) and without (FH-) a family history of alcoholism following the consumption of a placebo and real beer.

2. 2. FH+ subjects were less confident of being able to resist another drink following consumption of the placebo and reported higher taste ratings and feeling more intoxicated following ethanol consumption than FH- subjects.

3. 3. Both groups showed increases in EEG alpha activity (9–12Hz) following alcohol consumption.4. Alpha activity was positively associated with desire to drink in the FH+ group before and after consumption, but was positively associated with perceived intoxication in the FH- group only after consumption.

Associations of phenylthiocarbamide tasting to alcohol problems and family history of alcoholism differ by gender

Past research associating phenylthiocarbamide/propylthiouracil (PTC/PROP) taste status with alcoholism has produced equivocal results. Some have found higher proportions of nontasters among those with a family history of alcoholism than controls, whereas others have not. The purpose of this study was to investigate the relationship between PTC taste status, alcohol problems, and family history of alcoholism. A total of 244 undergraduate students participated in this study, with a gender distribution of 75% female and 25% male. We found support for our hypothesis that male supertasters would report fewer problems with alcohol and a less significant family history of alcoholism. Interestingly, we also found that female supertasters had a greater family history of alcoholism and more current problems associated with alcohol use. Implications for the genetic link between PTC taste status and alcoholism are discussed.     

mu-opioid receptor variants and dopaminergic sensitivity in alcohol withdrawal.

OBJECT: The endogenous opioid system plays an important role in the reinforcing properties of alcohol by an interconnected activation of the mesolimbic dopamine system. The Asn40Asp substitution polymorphism of the human mu-opioid-receptor (OPRM) influences binding of opioids and signal transduction and may, thereby, contribute to the development of alcoholism. The present study tested whether the Asn40Asp substitution polymorphism of the OPRM gene is associated with a variation in central dopaminergic sensitivity during alcohol withdrawal in alcoholics. METHOD: Sensitivity of central dopamine receptors was assessed by apomorphine-induced growth hormone (GH) secretion in 97 alcohol-dependent patients before and 1 week after alcohol cessation, and in a subgroup of 19 alcoholics after 3 months of abstinence. GH response was defined as area under the hormone/time curve. Comparisons of the GH response were conducted between alcoholics carrying the Asn40Asp genotype versus those with the Asn40Asn genotype using U-test statistics. RESULTS: Marginal differences in apomorphine-induced GH response were found between both genotype groups before detoxification (P = 0.799 (n = 97)/P = 0.459 (n = 19)) and after 3 months of abstinence (P = 0.331 (n = 19)). In contrast, the GH response measured seven days after alcohol withdrawal was significantly increased in alcoholics with the Asn40Asp genotype compared with those carrying the Asn40Asn genotype (P = 0.013 (n = 97)/P = 0.026 (n = 19)). CONCLUSION: Our results suggest that genetic variation of the mu-opioid receptor modulates the central dopaminergic sensitivity during acute alcohol withdrawal.     

A three-axes approach of subtyping the alcohol dependence syndrome

Subtyping of alcoholics according to specific characteristics has a long tradition in alcoholism research with a number of different typologies that emerged in the literature. The goal of the present study was to test a multidimensional approach of subtyping with characteristics from different axes. Therefore, male inpatients meeting ICD-10 criteria for alcohol dependence were rated on three axes by assessing their degree of sensation seeking (personality axis), age of alcoholism onset (clinical axis) and level of dopamine activity (neurobiological axis). By using a configuration frequency analysis, we identified a subtype that was characterized by high sensation seeking early age of alcoholism onset and high dopamine activity. This subtype, which is in accordance with clinical experience and cannot be explained by antisocial personality disorder, embodied a significantly greater proportion of alcoholics than expected. The result emphasizes the usefulness of multidimensional approaches integrating personality, clinical and neurobiological characteristics.     

DBH*444G/A polymorphism of the dopamine-β-hydroxylase gene is associated with alcoholism but not with severe alcohol withdrawal symptoms

Summary. As the enzyme dopamine-β-hydroxylase (DβH) converts dopamine to norepinephrine and both transmitters seem to be involved in the pathology of alcoholism and severe alcohol withdrawal symptoms, the gene encoding DβH (DBH) was applied to explore the genetic background of alcoholism and severe withdrawal symptoms. 102 healthy control subjects and 208 alcoholics, including 97 patients with a history of mild withdrawal symptoms, 57 with a history of alcohol withdrawal seizure (AWS) and 82 with a history of delirium tremens (DT) were genotyped for the DBH^*444G/A polymorphism revealing a significantly elevated frequency of genotypes carrying the A-allele (p = 0.02; after Bonferroni adjustment for multiple tests) in alcoholics compared to healthy controls. Frequencies of alleles and genotypes of individuals with mild withdrawal symptoms did not differ significantly from those of patients with DT or AWS.     

Neurocognitive impairment in patients with co-occurring bipolar disorder and alcohol dependence upon discharge from inpatient care

The current study explored the neurocognitive functioning of patients with co-occurring bipolar disorder and alcohol dependence upon discharge from inpatient care. The study compared scores of neuropsychological tests among three groups of bipolar I inpatients without a history of neurological injury or illness: 1) patients meeting DSM-IV diagnostic criteria for alcohol dependence in the past 6 months (n=13), 2) patients diagnosed with alcohol dependence in full remission (n=9), and 3) patients without a history of a substance use disorder (SUD; n=41). Analyses indicated that patients with co-occurring alcohol dependence exhibited more severe impairment on tests of executive functioning (i.e. Stroop Color-Word Interference Test, Wisconsin Card Sorting Test) than patients without SUD. In addition, the group meeting diagnostic criteria for alcohol dependence in the past 6 months exhibited greater decrements in verbal (California Verbal Learning Test--II) and visual (Rey Complex Figure Test) memory. Analysis further indicated that patients in full SUD remission scored lower on measures of fluid intelligence (Wechsler Abbreviated Scale of Intelligence--Performance IQ). Consistent with previous reports, in the current sample, co-occurring alcohol dependence predicted higher rates of disability status. It is possible that cognitive deficits of greater severity in dually diagnosed patients contribute to this unfavorable outcome. Recognizing the extent of cognitive impairment in dually diagnosed patients may facilitate the effort to ameliorate their condition.     

The cost of depression-complicated alcoholism: health-care utilization and treatment effectiveness

Clinical and epidemiologic evidence suggests that alcoholism complicated by concurrent or a lifetime history of depression is slower to remit and more prone to relapse than uncomplicated alcoholism. Consequently, alcoholics with a history of depressive illness, on average, are likely to use more health care and to have higher treatment costs than those without depression complications. This article contrasts evidence of the suitability of three models for predicting the impact of depression on an alcoholic's health-care use: a null model (assuming no differences), a cumulative-effect model (arguing for a linear increase associated with comorbid depression), and a synergistic model (wherein alcoholism complicated with depression is qualitatively as well as quantitatively different than uncomplicated alcoholism). To test these models, health-care costs and utilization of 491 "pure" alcoholics (those with no history of depression diagnosis) and 199 depression-complicated alcoholics, who received alcohol treatment while enrolled in a self-insured health-care program of a major U.S. manufacturing company, were compared. Results are discussed in terms of the implications for cost containment and the likelihood of relapse among the depression-complicated alcoholism group.     

Caffeine dependence in combination with a family history of alcoholism as a predictor of continued use of caffeine during pregnancy

OBJECTIVE: The purpose of the study was to examine whether caffeine dependence and a family history of alcoholism are associated with continued use of caffeine during pregnancy. METHOD: Forty-four women seeking obstetrical care in an office-based practice completed questionnaires and provided saliva samples at three prenatal visits occurring 2-3, 3-4, and 7 months postconception. On visit 1, the patients received the physician's instructions to stop using caffeine. Structured interviews were used to assign a diagnosis of caffeine dependence (lifetime) and to identify family history of alcoholism. Outcome measures included self-reported levels of caffeine use and saliva caffeine levels at the three prenatal visits. RESULTS: Although most women eliminated or substantially reduced their caffeine consumption between pregnancy awareness and prenatal visit 1, those with a lifetime diagnosis of caffeine dependence and a family history of alcoholism had higher levels of caffeine use and lower rates of abstinence throughout pregnancy. Saliva caffeine levels confirmed these effects. Withdrawal symptoms, functional impairment, and craving were cited as reasons they failed to eliminate or cut back on caffeine use. Fifty percent of the women with both a lifetime diagnosis of caffeine dependence and a family history of alcoholism continued to use caffeine in amounts (>300 mg/day) greater than those considered safe during pregnancy, compared to none of the women without caffeine dependence and a family history of alcoholism. Women with a lifetime diagnosis of caffeine dependence and a family history of alcoholism also reported higher rates of past cigarette smoking and problematic alcohol use. CONCLUSIONS: Caffeine-dependent women with a family history of alcoholism were not able to follow their physician's advice to reduce or eliminate caffeine consumption during pregnancy, despite their wanting to do so. This subgroup may require more intensive intervention to ensure caffeine abstinence and may be at greater risk for abuse of or dependence on other drugs.