Severity Of Alcohol Dependence Research Articles

Alexithymia, craving and attachment in a heavy drinking population

Up to fifty per cent of individuals with Alcohol use disorders (AUD) also have alexithymia a personality construct hypothesized to be related to attachment difficulties. The relationship between alexithymia, craving, anxious attachment and alcohol-dependence severity was examined in 254 patients participating in a Cognitive-Behavioral Therapy (CBT) program for alcohol-dependence. Participants completed the Toronto Alexithymia Scale (TAS-20), the Obsessive Compulsive Drinking Scale (OCDS), the Revised Adult Attachment Anxiety Subscale (RAAS-Anxiety) and the Alcohol Use Disorder Identification Test (AUDIT). MANOVA indicated that individuals with alexithymia reported significantly higher levels of total OCDS, obsessive thoughts about alcohol, and compulsive drinking urges and behavior, compared to the non-alexithymic group. Regression analyses found that anxious attachment partially mediated the relationship between alexithymia and craving. Anxious attachment may be a potential treatment target to reduce alcohol consumption in those with alcohol-dependence and alexithymia.

Prolactin Serum Levels During Alcohol Withdrawal Are Associated With the Severity of Alcohol Dependence and Withdrawal Symptoms

Prolactin serum levels have been described to be elevated during alcohol withdrawal in alcohol-dependent patients and normalize during abstinence. Alterations in prolactin levels may reflect disturbances of dopaminergic neurotransmission which is of crucial importance for alcohol-seeking behavior. In this longitudinal observational study, we investigated prolactin serum levels in 99 male patients during the first 14 days of alcohol withdrawal and early abstinence and in 43 healthy controls. To assess the severity of alcohol dependence, the extent of withdrawal symptoms, craving, depressive symptoms, and anxiety, we employed a structured interview including psychologic measurements. Prolactin serum levels were elevated during the whole study period in alcohol-dependent patients compared to the healthy control group. Prolactin levels at admission (first day of alcohol withdrawal) were associated with the severity of alcohol withdrawal (CIWA-Ar) and of alcohol dependence (SESA) but not with the other assessed psychologic parameters. The presented findings confirm that prolactin is significantly elevated in alcohol-dependent patients during alcohol withdrawal and early abstinence, not showing a rapid decline after cessation of drinking. The association with the severity of withdrawal and dependence may reflect at least partially the individual alterations in the dopaminergic and glutamatergic pathways.

Características diferenciales del alcoholismo femenino

Introduction: Alcoholic men and women have differential characteristics. It has been discussed whether alcoholic women have specific and additional difficulties that require extra study. However, these differences may imply an advantage for some aspects of treatment. Material and method: data from eleven published studies of alcoholic patients are reanalyzed from a gender perspective. Objective: to gain better knowledge of gender differences and their therapeutic implications. Results: women present more suicidal attempts than men, but these attempts are less lethal and have less intentionality. Personality structure is similar in the two sexes, but women have better prognosis, even if they present psychiatric disorders. A notable characteristic of women’s prognosis is their better adherence to group therapies. Women diagnosed with severe alcohol dependence who need inpatient treatment for detoxification are usually younger and have higher rates of benzodiazepine abuse and personality disorders than men, but are also more collaborative, and benefit more from therapy. Female benzodiazepine abusers show lower rates of neurocognitive impairment than men. Alcoholic women with severe organic conditions that require inpatient treatment usually have a medical record with more unsuccessful treatment attempts for alcohol dependence than men, and their prognosis is equally unfavourable. Conclusion: alcoholic women may have psychological mechanisms that facilitate higher abstinence rates and lower mortality rates than men. Future research for improving knowledge of such mechanisms, which are related to emotional factors such as guilt, depression and anxiety, and traditionally considered as problematic, may indicate that they actually increase motivation to change.

Limited Associations of Dopamine System Genes With Alcohol Dependence and Related Traits in the Irish Affected Sib Pair Study of Alcohol Dependence (IASPSAD)

Over 50 years of evidence from research has established that the central dopaminergic reward pathway is likely involved in alcohol dependence (AD). Additional evidence supports a role for dopamine (DA) in other disinhibitory psychopathology, which is often comorbid with AD. Family and twin studies demonstrate that a common genetic component accounts for most of the genetic variance in these traits. Thus, DA-related genes represent putative candidates for the genetic risk that underlies not only AD but also behavioral disinhibition. Many linkage and association studies have examined these relationships with inconsistent results, possibly because of low power, poor marker coverage, and/or an inappropriate correction for multiple testing. We conducted an association study on the products encoded by 10 DA-related genes (DRD1-D5, SLC18A2, SLC6A3, DDC, TH, COMT) using a large, ethnically homogeneous sample with severe AD (n = 545) and screened controls (n = 509). We collected genotypes from linkage disequilibrium (LD)-tagging single nucleotide polymorphisms (SNPs) and employed a gene-based method of correction. We tested for association with AD diagnosis in cases and controls and with a variety of alcohol-related traits (including age-at-onset, initial sensitivity, tolerance, maximum daily drinks, and a withdrawal factor score), disinhibitory symptoms, and a disinhibitory factor score in cases only. A total of 135 SNPs were genotyped using the Illumina GoldenGate and Taqman Assays-on-Demand protocols. Of the 101 SNPs entered into standard analysis, 6 independent SNPs from 5 DA genes were associated with AD or a quantitative alcohol-related trait. Two SNPs across 2 genes were associated with a disinhibitory symptom count, while 1 SNP in DRD5 was positive for association with the general disinhibitory factor score. Our study provides evidence of modest associations between a small number of DA-related genes and AD as well as a range of alcohol-related traits and measures of behavioral disinhibition. While we did conduct gene-based correction for multiple testing, we did not correct for multiple traits because the traits are correlated. However, false-positive findings remain possible, so our results must be interpreted with caution.

Clinical Predictors of Outcome from an Australian Pharmacological Relapse Prevention Trial

To assess which baseline characteristics of patients predict response to treatment with acamprosate (ACAMP) and naltrexone (NTX) in alcohol dependence. Outcome data from a 12-week randomized controlled trial of NTX, ACAMP and placebo for alcohol dependence were analysed by multiple logistic regression analyses to determine the predictive effects of gender and the baseline measures of dependence severity, craving, depression, anxiety and readiness to change in addition to NTX and ACAMP treatment. Moderators of the effect of each medication on outcomes were also examined. Relapse was predicted by the interaction terms of ACAMP and alcohol dependence severity, NTX and depression as well as NTX and the readiness to change measure Taking Steps. Abstinence was similarly predicted by the interaction term ACAMP and alcohol dependence severity. The efficacy of NTX and ACAMP in reducing relapse or lapse is influenced by different clinical characteristics.

Effect of Acamprosate on Magnetic Resonance Spectroscopy Measures of Central Glutamate in Detoxified Alcohol-Dependent Individuals

Acamprosate is approved for the treatment of alcoholism, but its mechanism of action remains unclear. Results of animal studies suggest that a persistent hyperglutamatergic state contributes to the pathogenesis of alcoholism and that acamprosate may exert its actions by intervening in this process. Human translation of these findings is lacking. To examine whether acamprosate modulates indices of central glutamate levels in recently abstinent alcohol-dependent patients as measured using proton nuclear magnetic resonance spectroscopy (¹H-MRS). A 4-week, double-blind, placebo-controlled, randomized controlled experimental medicine study, with ¹H-MRS measures obtained on days 4 and 25. An inpatient research unit at the NIH Clinical Center. Patients Thirty-three patients who met the DSM-IV criteria for alcohol dependence and who were admitted for medically supervised withdrawal from ongoing alcohol use. Intervention Four weeks of acamprosate (initial oral loading followed by 1998 mg daily) or matched placebo, initiated at the time of admission. The glutamate to creatine ratio as determined using single-voxel ¹H-MRS in the anterior cingulate. Exploratory neuroendocrine, biochemical, and behavioral outcomes were also collected, as were safety- and tolerability-related measures. There was a highly significant suppression of the glutamate to creatine ratio across time by acamprosate (time × treatment interaction: F₁(,)₂₉ = 13.5, P < .001). Cerebrospinal fluid levels of glutamate obtained in a subset of patients 4 weeks into abstinence were uncorrelated with the MRS measures and unaffected by treatment but were strongly correlated (R² = 0.48, P < .001) with alcohol dependence severity. Other exploratory outcomes, including repeated dexamethasone-corticotropin-releasing hormone tests, and psychiatric ratings were unaffected. Among tolerability measures, gastrointestinal symptoms were significantly greater in acamprosate-treated individuals, in agreement with the established profile of acamprosate. The MRS measures of central glutamate are reduced across time when acamprosate therapy is initiated at the onset of alcohol abstinence. clinicaltrials.gov Identifier: NCT00106106.

Getting to know Mark, a homeless alcohol-dependent artist, as he finds his way out of the river

Managed Alcohol Programs (MAPs) are a relatively recent addition to the repertoire of harm reduction approaches for persons experiencing severe alcohol dependence. In these settings, clients, who are typically homeless, are provided with a maintenance amount of alcohol while residing in a shelter setting. This case study examines the living experience of a homeless alcohol-dependent client of a MAP in an effort to articulate the process factors related to engagement with this form of treatment. The participant, a 48-year-old white male, participated in a series of qualitative interviews that took place prior to admission, immediately following admission, following re-admission, and after completion of the program over the course of 18 months. A grounded theory approach to data analysis was undertaken. The findings suggest that the primary utility of the MAP was in stabilizing a range of problems such that he was provided with the time, energy, and resources necessary to engage in the critically important task of constructing valued identity, place, and meaning and purpose in life.

Mental Disorders in Suicide and Undetermined Death in the Lundby Study. The Contribution of Severe Depression and Alcohol Dependence

To evaluate the role of severe depression, i.e., depression with melancholic and/or psychotic features and alcohol dependence in suicide and undetermined death. The Lundby Study is a prospective, longitudinal study of a population consisting of 3563 subjects. In a long-term follow up 1947–2006 there were 66 suicide cases, including 19 undetermined deaths. Depression and alcoholism were as expected the major contributors to suicide (44% and 23% respectively). Severe depression with psychotic and/or melancholic features was diagnosed in 66% of all depressions and in 29% of all suicide cases, as compared to 15% for major depression only. Alcohol dependence was related to undetermined death. Major depressive disorder with melancholic and/or psychotic features appears to be an important contributor to accomplished suicide in the depression group, and alcohol dependence appears to be related to undetermined death.

Matching motivation enhancement treatment to client motivation: re‐examining the Project MATCH motivation matching hypothesis

ABSTRACTAims The current study was designed to re‐examine the motivation matching hypothesis from Project MATCH using growth mixture modeling, an analytical technique that models variation in individual drinking patterns.Design, setting and participants Secondary data analyses of data from Project MATCH (n = 1726), a large multi‐site alcoholism treatment‐matching study.Measurements Percentage of drinking days was the primary outcome measure, assessed from 1 month to 12 months following treatment. Treatment assignment, alcohol dependence symptoms and baseline percentage of drinking days were included as covariates.Findings The results provided support for the motivation matching hypothesis in the out‐patient sample and among females in the aftercare sample: the majority of individuals with lower baseline motivation had better outcomes if assigned to motivation enhancement treatment (MET) compared to those assigned to cognitive behavioral treatment (CBT). In the aftercare sample there was a moderating effect of gender and alcohol dependence severity, whereby males with lower baseline motivation and greater alcohol dependence drank more frequently if assigned to MET compared to those assigned to CBT.Conclusions Results from the current study lend partial support to the motivation‐matching hypothesis and also demonstrated the importance of moderating influences on treatment matching effectiveness. Based upon these findings, individuals with low baseline motivation in out‐patient settings and males with low levels of alcohol dependence or females in aftercare settings may benefit more from motivational enhancement techniques than from cognitive–behavioral techniques.

Genetic Variation of the Ghrelin Signaling System in Females With Severe Alcohol Dependence

Central ghrelin signaling is required for the rewarding effects of alcohol in mice. Because ghrelin is implied in other addictive behaviors such as eating disorders and smoking, and because there is co-morbidity between these disorders and alcohol dependence, the ghrelin signaling system could be involved in mediating reward in general. Furthermore, in humans, single nucleotide polymorphisms (SNPs) and haplotypes of the pro-ghrelin gene (GHRL) and the ghrelin receptor gene (GHSR) have previously been associated with increased alcohol consumption and increased body weight. Known gender differences in plasma ghrelin levels prompted us to investigate genetic variation of the ghrelin signaling system in females with severe alcohol dependence (n = 113) and in a selected control sample of female low-consumers of alcohol from a large cohort study in southwest Sweden (n = 212). Six tag SNPs in the GHRL (rs696217, rs3491141, rs4684677, rs35680, rs42451, and rs26802) and four tag SNPs in the GHSR (rs495225, rs2232165, rs572169, and rs2948694) were genotyped in all individuals. We found that one GHRL haplotype was associated with reports of paternal alcohol dependence as well as with reports of withdrawal symptoms in the female alcohol-dependent group. Associations with 2 GHSR haplotypes and smoking were also shown. One of these haplotypes was also negatively associated with BMI in controls, while another haplotype was associated with having the early-onset, more heredity-driven, type 2 form of alcohol dependence in the patient group. Taken together, the genes encoding the ghrelin signaling system cannot be regarded as major susceptibility genes for female alcohol dependence, but is, however, involved in paternal heritability and may affect other reward- and energy-related factors such as smoking and BMI.

CLINICAL STUDY: BRIEF REPORT: Serum levels of vascular endothelial growth factor A increase during alcohol withdrawal

Vascular endothelial growth factor A (VEGF-A) is a key regulator of angiogenesis. This study investigated VEGF-A serum levels during alcohol withdrawal (days 1, 7 and 14, 76 male patients, 38 healthy controls). Patients showed significantly higher VEGF-A serum levels (t = 2.620, P = 0.010), which increased significantly during withdrawal (F = 4.484, P = 0.014, mean difference = -36.835, P = 0.037). The increase of VEGF-A serum levels was significantly associated with initial breath alcohol concentration and the sumscore of the severity scale of alcohol dependence (SESA questionnaire, F = 5.252, P = 0.008). Increase of VEGF-A serum levels is closely associated to alcohol intoxication and severity of alcohol dependence.

Treatments for Alcohol Dependence: Rethinking the Role of Comorbidity and Clinical Subtypes

Treatments for Alcohol Dependence: Rethinking the Role of Comorbidity and Clinical Subtypes

A systematic gene-based screen of chr4q22–q32 identifies association of a novel susceptibility gene, DKK2 , with the quantitative trait of alcohol dependence symptom counts

Studies of alcohol dependence (AD) have consistently found evidence of linkage on chromosome 4q21-q32. A genome-wide linkage scan in the Irish Affected Sib Pair Study of Alcohol Dependence (IASPSAD) sample also provided its strongest evidence of linkage on chromosome 4q22-q32 using an index of AD severity based on the count of DSM-IV AD symptoms (ADSX; LOD = 4.59). We conducted a systematic, gene-centric association study using 518 LD-tagging single nucleotide polymorphisms (SNPs) in the 65 known and predicted genes within the 1-LOD interval surrounding the linkage peak. Case-only regression analysis with the quantitative variable of ADSX was performed in the 562 genetically independent cases; nominal support for association was demonstrated by 32 tagging SNPs in 14 genes. We did not observe study-wide significance, but gene-wise correction for multiple testing with the Nyholt procedure yielded empirical evidence of association with two genes, DKK2 (dickkopf homolog 2) (P = 0.007) and EGF (epidermal growth factor) (P = 0.025) in the IASPSAD sample. Three SNPs in DKK2 (rs427983; rs419558; rs399087) demonstrated empirical significance. Assessment of possible replication in 847 cases of European descent from a large independent sample, the Collaborative Study of the Genetics of Alcoholism, yielded replication for DKK2 but not EGF. We observed genotypic and phenotypic replication for DKK2 with the three SNPs yielding significant association with ADSX in the IASPSAD sample. Haplotype-specific expression measurements in post-mortem tissue samples suggested a functional role for DKK2. This evidence notwithstanding, replication is needed before confidence can be placed in these findings.

Childhood antecedents of adult violent offending in a group of female felons

The purpose of this study was to evaluate potential antecedents of violent felony arrest in a sample of female felons. Among male populations, early onset conduct disorder (CD) with progression to adult anti-social personality disorder (ASPD) is associated with increased criminality and aggression. Conduct disorder is associated with a worsened trajectory of alcohol dependence in men. These factors likely have a synergistic contribution to male adult violent offending. Existing work suggests that CD, ASPD, and severe alcohol dependence may represent an externalizing endophenotype, which is, at least in part, genetically conferred. These associations have not been well studied in female populations. The author examined a sample (N = 130) of female mid-sentence felons to determine associations between adult arrest for violent felony with child and young adult antecedents, including CD and alcohol dependence. Data were gathered through administration of the Semi-Structured Assessment for the Genetics of Alcoholism II (SSAGA II). CD had high prevalence (40.8%), as did ASPD (31.4%) and alcohol dependence (43.8%). Women convicted of violent felonies were more likely to have CD with progression to ASPD, and alcohol dependence. Both alcohol dependence and CD were independently associated with violent offending. These data suggest that the most serious female offenders have psychopathology similar to that of males and that the trajectory of disease and etiology of violent behavior may not be as gender specific as previously presumed.

Deep brain stimulation of the nucleus accumbens is effective for the treatment of severe alcohol dependence

Introduction: Alcohol dependence is one of the worldwide leading modifiable causes of morbidity and death. The treatment of alcohol dependency rests on pharmacological, psychological and social therapeutic interventions whilst none of these interventions can be considered reliably and permanently effective.1

Effectiveness and Safety of Baclofen in the Treatment of Alcohol Dependent Patients

Both preclinical and clinical research studies have shown the GABA(B) receptor agonist baclofen represents a promising treatment for alcohol dependence. Preliminary clinical studies indicate that baclofen is able to suppress withdrawal symptoms in alcohol-dependent patients affected by the alcohol withdrawal syndrome. Moreover, baclofen has shown efficacy and safety in promoting alcohol abstinence in alcohol dependent patients in two placebo-controlled trials including one in alcohol-dependent patients with liver cirrhosis. These trials also demonstrated that baclofen was associated with reductions in withdrawal-related anxiety and alcohol craving. However, more work is needed to clearly demonstrate the efficacy of baclofen and to ascertain whether efficacy is limited to certain subtypes of alcoholic patients. For example, a recent US trial failed to demonstrate a robust effect of baclofen in treating alcohol-dependent patients though the relative moderate severity of alcohol-dependence in that trial has been suggested as one factor that may have contributed to the finding. In the present review, the authors will summarize the published clinical studies on the role of baclofen in alcohol dependence and will also present some unpublished secondary analyses. Finally, the authors will discuss possible future directions to further investigate the role of baclofen in alcohol dependence (e.g., baclofen's biobehavioral mechanisms, different baclofen doses, differences in severity and in alcoholic subtypes, different formulations of baclofen, possible combination of baclofen with other medications).

Alcohol and Depression

‘Problem drinking’ is a major national concern as it can lead to long-term serious physical and mental health problems. Alcohol can mimic or accentuate many of the symptoms of depression: low mood, low energy, changes in appetite, weight or sleep pattern, poor concentration, feelings of guilt or worthlessness and suicidal ideation. Many people with depression can develop an alcohol problem as they may ‘self-medicate’ to feel more energetic or cheerful. In severe cases, alcohol misuse can lead to impaired judgement and increase the risk of suicide. Patients with severe depression and alcohol dependence coexisting are considered to have a ‘dual diagnosis’ and often require support from mental health specialist services such as community alcohol team in addition to primary care support.

PW01-250 - Addressing self-image distorsions as a core feature in the alcohol dependence psychoterapeutic approach

ObjectiveTo establish the frequency of self-image distorsions in alcohol dependent patients and if addressing them through a targeted psychotherapeutic approach would be beneficial.MethodsA group of 45 patients, 32 male and 13 female, mean age 39.6, diagnosed with alcohol dependence (DSM IV TR), were evaluated for establishing the severity of self-image distorsions, using-baseline and endpoint- Rotter Incomplete Sentence Test (RIST) and Thematic Apperception Test (TAT); for the monitoring of the dependence severity and its associated impairments we used Inventory of Drug Taking Situations (IDTS)-alcohol focused version and Global Assessment of Function (GAF) every 4 weeks for 6 months. From the initial group, 38 (84.4%) patients have been found with moderate and severe self-image distorsions (feeling of insecurity and inferiority, external locus of control, frequent use of denial, regression and projection). They received cognitive-behavior therapy (CBT) focused on restructuring cognitive dysfunctional beliefs about self and experimenting new ways to relate to self and significant others.ResultsThe psychotherapeutic approach decreased the overall severity of alcohol dependence (-35.7 on IDTS, p&lt; 0.01) and consequently improved the global functioning (+18.2 on GAF, p&lt; 0.01) after 6 months. These results correlated with the improvement of self-image, reflected on the severity of P-Ego scale from RIST (-23.2%, p&lt; 0.01) and on the improvement of defense system (more frequent use of anticipation, suppression and rationalization and less of denial and projection).ConclusionPatients with alcohol dependence have very often self-image distorsions and could, therefore, benefit from a psychotherapy that addresses specifically this phenomenon.

Neuropsychological Impairment and Relapse following Inpatient Detoxification in Severe Alcohol Dependence

The aim of the study was to examine the relationship between neuropsychological impairment in severe alcohol dependence and relapse. This was assessed following inpatient detoxification over a period of three months. Participants were tested on measures of neuropsychological functioning at the end of a seven to ten day stay in an inpatient alcohol detoxification unit. Participants were followed up three months later by telephone to ascertain the number of days in which alcohol was consumed during this period using the Timeline Follow Back procedure (TLFB). A correlation and regression design was used to analyse results. An inpatient alcohol detoxification unit. Thirty-four residents in an inpatient alcohol detoxification unit. Executive dysfunction during detoxification was found to predict number of days drinking in the three months following discharge. Neuropsychological impairment, and specifically executive dysfunction, appears to be a significant barrier to ability to remain abstinent from alcohol following a period of detoxification. Given the high rates of relapse found within the current study it suggests that the cognitive domains that executive functioning describe are particularly relevant in facilitating abstinence in alcohol dependence.

Gender Differences in Interpersonal Problems of Alcohol-Dependent Patients and Healthy Controls

Alcohol dependence is a heavy burden on patients, their families, and society. Epidemiological studies indicate that alcohol dependence will affect many individuals at some time in their lives, with men affected more frequently than women. Since alcohol-dependent patients often exhibit a lack of social skills and suffer from interpersonal problems, the aim of this study is to elucidate whether men and women experience the same interpersonal problems. Eighty-five alcohol-dependent patients (48 men; 37 women) after detoxification and 62 healthy controls (35 men; 27 women) were recruited. Interpersonal problems were measured with the Inventory of Interpersonal Problems (IIP-64). Additionally, alcohol-dependent patients were interviewed with the Alcohol Use Disorders Identification Test (AUDIT) and were subtyped according to Lesch’s Alcohol Typology (LAT). There were no significant gender differences in the AUDIT and LAT between alcohol-dependent men and women. Interpersonal problems of alcohol-dependent men differed significantly in one out of eight dimensions from controls; alcohol-dependent men perceive themselves as colder than male controls. Alcohol-dependent women differed in four out of eight interpersonal dimensions from female controls. Alcohol-dependent women rated themselves as significantly more vindictive, more introverted, more overly accommodating and more intrusive than female controls. Results suggest that alcohol-dependent men and women suffer from different interpersonal problems and furthermore alcohol-dependent women perceive more interpersonal problems, whereas the severity of alcohol dependence did not differ between the groups. Our findings indicate that alcohol-dependent women may profit more from a gender-specific treatment approach aimed at improving treatment outcome than alcohol-dependent men.