DSM-IV Criteria For Alcohol Dependence Research Articles

Naltrexone vs Placebo for the Treatment of Alcohol Dependence: A Randomized Clinical Trial.

Alcohol use disorder is one of the leading causes of disability worldwide. While effective pharmacological treatments exist, they are efficacious only in certain individuals, contributing to their limited use. Secondary analysis of clinical trial data suggests that a functional polymorphism (rs1799971, Asn40Asp) of the µ-opioid receptor gene (OPRM1) is associated with the risk of relapse to heavy drinking following treatment with the opioid antagonist naltrexone. To prospectively examine whether rs1799971 is predictive of naltrexone treatment response. We conducted a 12-week, double-blind, randomized clinical trial of naltrexone vs placebo in individuals with alcohol dependence (intent-to-treat analysis). Participants were randomly assigned to study treatment based on the presence of 1 or 2 copies of the Asp40 allele compared with those homozygous for the Asn40 allele (2 × 2 cell design). Recruitment occurred between January 2009 and September 2013. All participants were seen in an outpatient clinical setting. A convenience sample of participants (n = 221) was recruited from 5 sites. All participants met DSM-IV criteria for alcohol dependence, with no concurrent psychotic or manic symptoms, no use of concurrent psychotropic medications, and no current dependence on illicit substances. The study drug was naltrexone (50 mg) given once daily or corresponding placebo. The primary study outcome measure was relapse to heavy drinking measured using the timeline follow-back method. There was no evidence of a genotype × treatment interaction on the primary outcome of heavy drinking (P = .32). In the Asn40 group, the observed effect of naltrexone was similar to that in previous trials (odds ratio, 0.69; 95% CI, 0.41-1.18; P = .17), with a very small naltrexone effect in the Asp40 group (odds ratio, 1.10; 95% CI, 0.52-2.31; P = .80), contrary to the pattern expected a priori. A significant reduction in heavy drinking occurred across all groups (P = .001). Other drinking outcomes, and all secondary outcomes, demonstrated similar time effects, with no genotype × treatment interaction. The results of this study do not support the hypothesis that the Asp40 allele moderates the response to naltrexone treatment. It is premature to use the Asn40Asp polymorphism as a biomarker to predict the response to naltrexone treatment of alcohol dependence. clinicaltrials.gov Identifier: NCT00831272.

Changes on the Modulation of the Startle Reflex in Alcohol-Dependent Patients after 12 Weeks of a Cognitive-Behavioral Intervention

Aims: Little is known about changes in the modulation of the startle reflex when patients go through an alcohol-dependence treatment in an outpatient facility. In the current study, the affective modulation of the cue-related startle reflex has been used to evaluate changes in the emotional processing of alcohol-related stimuli that occurred after a standard cognitive-behavioral intervention, and to assess the outcome of this intervention. We hypothesized a ‘normalization' of the startle inhibition for the alcohol-related cues during the period of treatment. We also assumed that higher startle inhibition at baseline elicited by alcohol cues would predict the relapse on alcohol consumption during treatment. Participants: A total of 98 alcohol-dependent subjects were included who fulfilled DSM-IV criteria for alcohol dependence. A control group of 72 subjects was selected to match demographic characteristics. Measurements: All patients received a standard cognitive-behavioral therapy once a week throughout the study period. Findings: Results show that the startle response differed significantly after 12 weeks of treatment for alcohol-related, neutral and aversive stimuli between alcohol-dependent patients and controls. Low startle responses at baseline to alcohol cues predicted relapse. Conclusions: These results may indicate that the startle reflex is referred to enduring and permanent processes of cue reactivity, and that the emotional processing of alcohol-associated cues assessed with the affect-modulated startle reflex is less altered by interventions attempting to influence explicit cognitions. Furthermore, lower values of the baseline startle reflex elicited by alcohol-associated stimuli were associated with higher probability of relapse on alcohol use.

Genome-wide association data suggest ABCB1 and immune-related gene sets may be involved in adult antisocial behavior.

Adult antisocial behavior (AAB) is moderately heritable, relatively common and has adverse consequences for individuals and society. We examined the molecular genetic basis of AAB in 1379 participants from a case–control study in which the cases met criteria for alcohol dependence. We also examined whether genes of interest were expressed in human brain. AAB was measured using a count of the number of Antisocial Personality Disorder criteria endorsed under criterion A from the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV). Participants were genotyped on the Illumina Human 1M BeadChip. In total, all single-nucleotide polymorphisms (SNPs) accounted for 25% of the variance in AAB, although this estimate was not significant (P=0.09). Enrichment tests indicated that more significantly associated genes were over-represented in seven gene sets, and most were immune related. Our most highly associated SNP (rs4728702, P=5.77 × 10−7) was located in the protein-coding adenosine triphosphate-binding cassette, sub-family B (MDR/TAP), member 1 (ABCB1). In a gene-based test, ABCB1 was genome-wide significant (q=0.03). Expression analyses indicated that ABCB1 was robustly expressed in the brain. ABCB1 has been implicated in substance use, and in post hoc tests we found that variation in ABCB1 was associated with DSM-IV alcohol and cocaine dependence criterion counts. These results suggest that ABCB1 may confer risk across externalizing behaviors, and are consistent with previous suggestions that immune pathways are associated with externalizing behaviors. The results should be tempered by the fact that we did not replicate the associations for ABCB1 or the gene sets in a less-affected independent sample.

Genetic influences on alcohol use behaviors have diverging developmental trajectories: a prospective study among male and female twins.

Both alcohol-specific genetic factors and genetic factors related to externalizing behavior influence problematic alcohol use. Little is known, however, about the etiologic role of these 2 components of genetic risk on alcohol-related behaviors across development. Prior studies conducted in a male cohort of twins suggest that externalizing genetic factors are important for predicting heavy alcohol use in adolescence, whereas alcohol-specific genetic factors increase in importance during the transition to adulthood. In this report, we studied twin brothers and sisters and brother-sister twin pairs to examine such developmental trajectories and investigate whether sex and cotwin sex effects modify these genetic influences. We used prospective, longitudinal twin data collected between ages 12 and 22 within the population-based FinnTwin12 cohort study (analytic n=1,864). Our dependent measures of alcohol use behaviors included alcohol initiation (age 12), intoxication frequency (ages 14 and 17), and alcohol dependence criteria (age 22). Each individual's genetic risk of alcohol use disorders (AUD-GR) was indexed by his/her parents' and cotwin's DSM-IV Alcohol Dependence (AD) criterion counts. Likewise, each individual's genetic risk of externalizing disorders (EXT-GR) was indexed with a composite measure of parents' and cotwin's DSM-IV Conduct Disorder and Antisocial Personality Disorder criterion counts. EXT-GR was most strongly related to alcohol use behaviors during adolescence, while AUD-GR was most strongly related to alcohol problems in young adulthood. Further, sex of the twin and sex of the cotwin significantly moderated the associations between genetic risk and alcohol use behaviors across development: AUD-GR influenced early adolescent alcohol use behaviors in females more than in males, and EXT-GR influenced age 22 AD more in males than in females. In addition, the associations of AUD-GR and EXT-GR with intoxication frequency were greater among 14- and 17-year-old females with twin brothers. We found divergent developmental trajectories for alcohol-specific and externalizing behavior-related genetic influences on alcohol use behaviors; in early adolescence, genetic influences on alcohol use behaviors are largely nonspecific, and later in adolescence and young adulthood, alcohol-specific genetic influences on alcohol use are more influential. Importantly, within these overall trajectories, several interesting sex differences emerged. We found that the relationship between genetic risk and problematic drinking across development is moderated by the individual's sex and his/her cotwin's sex. AUD-GR influenced adolescent alcohol outcomes in females more than in males and by age 22, EXT-GR influenced AD criteria more for males than females. In addition, the association between genetic risk and intoxication frequency was greater among 14- and 17-year-old females with male cotwins.

A Study on MTHFR C677T Gene Polymorphism and Alcohol Dependence among Meiteis of Manipur, India.

Chronic alcohol consumption is reported to be associated with increase in plasma homocysteine levels which is further influenced by the polymorphism in methylenetetrahydrofolate reductase (MTHFR) gene. The present study aims to understand the extent of the MTHFR C677T polymorphism in alcohol dependent (AD) cases of Meiteis of Manipur, a Mendelian population of India. MTHFR C677T polymorphism was screened in 313 controls and 139 alcohol dependent (AD) cases who all met DSM-IV criteria for alcohol dependence. Both AD cases and controls were unrelated up to 1st cousin. Among the control group, different drinking patterns like abstainer/nondrinkers (NDs), occasional drinkers (ODs), and moderate drinkers (MDs) are included. Both the groups were found to be in Hardy-Weinberg equilibrium (P > 0.05). Genotypic and allelic frequency distribution of MTHFR C677T polymorphism did not differ significantly between AD cases and controls (P > 0.05). However, individuals carrying mutant (T) allele show more than 1-fold increased risk for AD though not significant (OR = 1.43; 95% CI 0.41–5.01, P > 0.05). In conclusion, MTHFR C677T polymorphism is not found to be risk marker for AD in present studied population. However, higher prevalence of the mutant T allele may exacerbate deleterious health risk in future especially among alcohol drinkers.

SY05-4 * THE IMPACT OF THE GREAT EAST JAPAN EARTHQUAKE ON ALCOHOL, NICOTINE AND HYPNOTIC ABUSE AND GAMBLING IN DISASTER-STRICKEN AREAS

Introduction. A huge earthquake and resulting tsunami struck north-eastern Japan in 2011 and caused widespread damage. It is believed that mental health problems, including substance abuse, increased in the area after the disaster. Subjects and Methods. The subjects were 3600 people living where the damage caused by the tsunami was most severe and 2000 people living outside the disaster-stricken areas. Interviewers asked about drinking and smoking and also conducted semi-structured interviews based on the questionnaires which allowed the determination of whether subjects met the DSM-IV criteria for alcohol dependence. The following self-reporting questionnaires were asked: AUDIT, FTND, BDEPQ and SOGS. Results. The prevalence of tobacco and hypnotic use and the frequency of subjects with high FTND and BDEPQ scores were higher in the coastal female group than the remaining two groups. The frequency of heavy alcohol use was associated with unemployment due to the disaster. The percentage of subjects with high SOGS scores was highest in the coastal area male group than the remaining two groups. Conclusion. These results suggest that, in the disaster-stricken area, alcohol related problems and pathological gambling are increased in men while hypnotic and nicotine dependence is increased in women.

A Smartphone Application to Support Recovery From Alcoholism

Patients leaving residential treatment for alcohol use disorders are not typically offered evidence-based continuing care, although research suggests that continuing care is associated with better outcomes. A smartphone-based application could provide effective continuing care. To determine whether patients leaving residential treatment for alcohol use disorders with a smartphone application to support recovery have fewer risky drinking days than control patients. An unmasked randomized clinical trial involving 3 residential programs operated by 1 nonprofit treatment organization in the Midwestern United States and 2 residential programs operated by 1 nonprofit organization in the Northeastern United States. In total, 349 patients who met the criteria for DSM-IV alcohol dependence when they entered residential treatment were randomized to treatment as usual (n = 179) or treatment as usual plus a smartphone (n = 170) with the Addiction-Comprehensive Health Enhancement Support System (A-CHESS), an application designed to improve continuing care for alcohol use disorders. Treatment as usual varied across programs; none offered patients coordinated continuing care after discharge. A-CHESS provides monitoring, information, communication, and support services to patients, including ways for patients and counselors to stay in contact. The intervention and follow-up period lasted 8 and 4 months, respectively. Risky drinking days--the number of days during which a patient's drinking in a 2-hour period exceeded 4 standard drinks for men and 3 standard drinks for women, with standard drink defined as one that contains roughly 14 g of pure alcohol (12 oz of regular beer, 5 oz of wine, or 1.5 oz of distilled spirits). Patients were asked to report their risky drinking days in the previous 30 days on surveys taken 4, 8, and 12 months after discharge from residential treatment. For the 8 months of the intervention and 4 months of follow-up, patients in the A-CHESS group reported significantly fewer risky drinking days than did patients in the control group, with a mean of 1.39 vs 2.75 days (mean difference, 1.37; 95% CI, 0.46-2.27; P = .003). The findings suggest that a multifeatured smartphone application may have significant benefit to patients in continuing care for alcohol use disorders. clinicaltrials.gov Identifier: NCT01003119.

Yoga as an adjunct treatment for alcohol dependence: A pilot study

This pilot study explores the feasibility of yoga as part of a treatment program for alcohol dependence. Eighteen alcohol dependent patients were randomized to receive either treatment as usual or treatment as usual plus yoga. Assessments were taken at baseline and six month follow-up. 'Riddargatan 1': an outpatient alcohol treatment clinic located in Stockholm, Sweden. Treatment as usual consisted of psychological and pharmacological interventions for alcohol dependence. The 10-week yoga intervention included a weekly group yoga session. Participants were encouraged to practice the yoga movements at home once per day. Alcohol consumption (timeline follow-back method, DSM-IV criteria for alcohol dependence, and the Short Alcohol Dependence Data questionnaire), affective symptoms (the Hospital Anxiety and Depression Scale), quality of life (Sheehan Disability Scale) and stress (the Perceived Stress Scale and saliva cortisol). Yoga was found to be a feasible and well accepted adjunct treatment for alcohol dependence. Alcohol consumption reduced more in the treatment as usual plus yoga group (from 6.32 to 3.36 drinks per day) compared to the treatment as usual only group (from 3.42 to 3.08 drinks per day). The difference was, however, not statistically significant (p = 0.17). Larger studies are needed to adequately assess the efficacy and long-term effectiveness of yoga as an adjunct treatment for alcohol dependence.

Trajectories of alcohol use over time among adults with alcohol dependence

This study sought to identify trajectories of drinking behavior change over time in a sample of adults with current alcohol use disorder (AUD). We conducted secondary analyses of seven waves of data from a prospective longitudinal study of 364 adults (mean age=44.0years, SD=12.8years) who met criteria for DSM-IV alcohol dependence (AD), 74.4% of whom were entering alcohol treatment. Participants were followed for 2 1/2 to 3years with in-person interviews every 6months. Results from latent class growth analyses of drinks per drinking day over 3years indicated five trajectory classes: 1) Moderate Baseline→Slow Decline; 2) Heavy Baseline→Stable Abstinent; 3) Heavy Baseline→Slow Decline; 4) Heaviest Baseline→Steep Decline, and 5) Heaviest Baseline→Stable Heavy. Findings are consistent with previous research and suggest that these trajectory classes might represent longitudinal phenotypes of alcohol involvement across diverse samples. Treatment modality, Alcoholics Anonymous involvement, and purpose in life were associated with diverse trajectories of drinking behavior among adults with AD. AA involvement was associated with higher odds of membership in trajectory classes that showed declines in drinking from baseline, and having higher purpose in life predicted lower odds of membership in the Heaviest Baseline→Stable Heavy class. AA involvement predicts different pathways of recovery characterized by stable abstinence, steep declines, and/or slower declines in drinking over time. Higher purpose in life may protect against chronic heavy drinking by strengthening motivations to pursue goals that are unrelated to substance use.

New and Old Drugs to Treat Alcohol Use Disorders

Around 2 billion people consume alcoholic beverages worldwide, and almost 10% of the world’s population is affected by AlcoholUse Disorders (AUDs) [1]. Alcohol consumption is responsible for approximately 3.8% of all deaths [2] and accounts for 5.5% of the global burden of disease [3]. So far, only three drugs [Naltrexone (NTX), Acamprosate (ACM), and Disulfiram (DF)] have been approved by the Food and Drug Administration for the treatment of alcohol dependence [4]; however, emerging data from clinical trials suggest that these medications are relatively ineffective in maintaining the abstinence from alcohol. The predict study conducted in Germany by Mann et al. [5] clearly documented that neither ACM nor NTX are more efficient than placebo in reducing the number of relapses throughout the complete treatment period and the subsequent 18 months of follow-up. The results of the predict study have been compared with those of the COMBINE trial performed in the United States (US) [6]. The main outcome of the predict study was the time elapsed before the first episode of heavy drinking, and, contrary to the positive NTX effect reported by the combine study, neither ACM nor NTX provided an additional benefit compared with placebo. It is worth noting that patients drank a significantly greater amount of alcohol before enrolment and more often fulfilled DSM-IV criteria for alcohol dependence in the predict than in the combine study, suggesting that the patient populations included in these trials were substantially different. A similar lack of efficacy also emerged from a previous European trial where NTX plus ACM were more effective than placebo and ACM alone in reducing episodes of heavy drinking, but not NTX alone [7]. A meta-analysis published a few years ago [8] stated that neither NTX nor ACM were able to maintain complete abstinence from alcohol; rather, these agents are effective in reducing relapses and the number of drinks per drinking days, and, consequently, the organ damage caused by alcohol consumption. The main aim in treating alcohol dependence is complete abstinence. In the light of the results of the studies reported above, ACM and NTX should be rationally indicated only when this purpose cannot be achieved, with the aim of reducing alcohol intake and, therefore, achieve a “harm reduction”. Indeed, total abstinence was obtained in an equivalent proportion of patients both in predict and combine studies, i.e. 39.3% and 38.9% respectively. Nevertheless, NTX and ACM remain the first line of pharmacological treatment for alcohol dependence. Are there any other pharmacological possibilities? An interesting position was expressed by Jonathan Chick and David Nutt in their “perspective” paper which appeared in 2011: “For a condition where existing therapies are only effective in a proportion of patients, and which has high morbidity and mortality, the time now seems right for reappraising the use of substitute prescribing for alcohol dependence” [9].

Differences in Executive Functions and Problem Solving Styles of Protracted Sober and Relapsed Alcohol-dependent Patients

In this study, it is aimed to compare the executive functioning and problem solving styles of relapsed alcoholdependent and protracted sober patients and to evaluate the potential clinical factors that act on the duration of sobriety. Fifty-six male patients meeting the DSM-IV alcohol dependence criteria included in the study. All patients were in sobriety period, classified as 32 of them in acute sobriety (relapsed after a maximum period of 6 months sobriety and just completed 3 weeks of detoxification) and 24 of them as protracted sobriety group (sober for a minimum period of 12 months). To evaluate the executive functions and problem solving styles Stroop test, Hanoi Tower Test and Problem Solving Inventory were applied. No significant differences found between two groups regarding executive functions. The protracted sobers were found to use “reflective” and “planfulness” styles more than the relapsed group. There was not any correlation between executive function and cumulative drinking, length of sobriety, educational status, age, alcohol dependency in the family, duration of illness, the amount of daily drinking, and amount of hospitalization. It is concluded that problem solving styles may play a role in staying sober as the “reflective” and “planfulness” styles were being used significantly more in the protracted sober group. Executive functioning which had been shown to be distorted in alcohol-dependent patients did not differ in relapsed and protracted sobriety. Further studies are needed to receive these results to be a determinant in the duration of sobriety.

Family-based association analysis of alcohol dependence criteria and severity.

Despite the high heritability of alcohol dependence (AD), the genes found to be associated with it account for only a small proportion of its total variability. The goal of this study was to identify and analyze phenotypes based on homogeneous classes of individuals to increase the power to detect genetic risk factors contributing to the risk of AD. The 7 individual DSM-IV criteria for AD were analyzed using latent class analysis (LCA) to identify classes defined by the pattern of endorsement of the criteria. A genome-wide association study was performed in 118 extended European American families (n=2,322 individuals) densely affected with AD to identify genes associated with AD, with each of the 7 DSM-IV criteria, and with the probability of belonging to 2 of 3 latent classes. Heritability for DSM-IV AD was 61% and ranged from 17 to 60% for the other phenotypes. A single nucleotide polymorphism (SNP) in the olfactory receptor OR51L1 was significantly associated (7.3×10(-8) ) with the DSM-IV criterion of persistent desire to, or inability to, cut down on drinking. LCA revealed a 3-class model: the "low-risk" class (50%) rarely endorsed any criteria and none met criteria for AD; the "moderate-risk" class (33%) endorsed primarily 4 DSM-IV criteria and 48% met criteria for AD; and the "high-risk" class (17%) manifested high endorsement probabilities for most criteria and nearly all (99%) met criteria for AD. One SNP in a sodium leak channel NALCN demonstrated genome-wide significance with the high-risk class (p=4.1×10(-8) ). Analyses in an independent sample did not replicate these associations. We explored the genetic contribution to several phenotypes derived from the DSM-IV AD criteria. The strongest evidence of association was with SNPs in NALCN and OR51L1.

Barriers to treatment for alcohol dependence: a qualitative study

Approximately half of all people with high alcohol consumption in Sweden fulfill criteria for either harmful consumption or dependence. Among the alcohol-dependent, the majority have dependence with low severity. They are also reluctant to seek treatment. This qualitative study, with data from seven focus group discussions and 14 individual interviews, aims to describe and explain how representations of alcohol consumption, dependence, and treatment create barriers to treatment. Thirty-two adults from the general population fulfilling DSM-IV criteria for alcohol dependence participated. Most of the participants agreed that they were heavy drinkers but did not perceive themselves as alcohol dependent. Having alcohol problems, as well as realizing the need for and entering treatment, was associated with shame and stigma, producing a strong barrier to treatment. The participants’ knowledge about treatment was limited and somewhat faulty, as they thought that treatment mainly involves medication with disulfiram, lifelong abstinence, and inpatient care at rehabilitation clinics. As these treatments are socially restrictive and stigmatizing, this understanding created a barrier to treatment. While treatment for alcohol problems in primary care was seen as less stigmatizing, the expertise among general practitioners in this field was questioned. Results indicate that, to lower the threshold for treatment seeking, treatment services need to better match the needs and wishes of the potential service users as well as take stigmatization into account. Primary care practices and general practitioners need to market their ability to treat people with drinking problems. The clinical understanding of alcohol dependence needs to be expanded to include mild to moderate dependence, conditions which can be managed in primary care.

Using Latent Variable Techniques to Understand DSM-IV Alcohol Use Disorder Criteria Functioning

To use factor analytic and item response theory methods to understand diagnostic Alcohol Use Disorder (AUD) criteria functioning in non-college young adults. The current study examined data from the 2009 National Survey of Drug Use and Health. Participants were non-college attending young adults (18 to 25) who consumed alcohol in the prior year. Confirmatory factor analysis (CFA) and item response theory (IRT) techniques were used to assess the dimensionality of DSM-IV AUD criteria. CFA results indicated a dominant single factor, whereas IRT difficulty parameters revealed that the difficulty (severity) parameter estimates were intermixed across the latent AUD continuum. Findings are consistent with research showing that the DSM-IV alcohol abuse and dependence criteria should be combined into a single disorder.

Assessment of a Modified DSM‐5 Diagnosis of Alcohol Use Disorder in a Genetically Informative Population

Proposed changes to the upcoming DSM-5 include the following: (i) combining criteria for DSM-IV alcohol abuse (AA) and alcohol dependence (AD) into 1 diagnostic category (alcohol use disorder [AUD]); (ii) exclusion of the "legal problems" (LP) criterion; and (iii) addition of a "craving" criterion. Few published studies empirically assess the potential consequences of the proposed changes. Using a population-based sample of twins assessed for lifetime AA/AD diagnoses, we explored phenotypic differences across DSM-IV and a modified DSM-5 diagnoses without craving because of its unavailability in the data set. We used factor analysis and item response theory (IRT) to evaluate the potential consequences of excluding the LP criterion from AUD and used twin modeling to examine genetic differences between DSM-IV and the modified DSM-5 diagnoses. The prevalence of AUD was slightly higher than that of DSM-IV diagnoses. Individuals meeting DSM-IV or DSM-5 criteria, but not both, exhibit fewer comorbid diagnoses than those meeting both sets of criteria. Individuals meeting only DSM-5 criteria were slightly less severely affected than those meeting only DSM-IV criteria. Factor analysis indicated that the LP criterion loading is the lowest of all symptoms; IRT analysis suggested that this criterion has low discriminatory power. The genetic correlation between DSM-IV and DSM-5 diagnoses was slightly but significantly lower than unity. The proposed DSM-5 AUD criteria are unlikely to result in significant changes in prevalence of diagnosed alcohol problems. However, it is unclear whether the new criteria represent a more valid diagnosis: new cases are no more severely affected than DSM-IV-only cases. Given the psychometric properties of LP, its exclusion should not negatively impact diagnostic validity. Similarly, the stable heritability across DSM-IV and DSM-5 diagnoses suggests that the proposed changes will not have substantial negative consequences in terms of familial influences, a key validator. These results provide equivocal empirical support for the proposed DSM-5 changes for AUDs.

2015 – Impulsivity and stress as risk factors for the development of alcohol dependence

Introduction It is well known that impulsivity and stress are risk factors for the development of addictive disorders, and more specifically alcohol dependence. Impulsivity has two dimensions: behavioural inhibition and delay of reward. The Fear- Conditioning paradigm of the Startle response (SR), which refers to the potentiation of the startle amplitude after the exposure to aversive stimulus, can be used as a stress test. The aim of this study was to explore the correlation between impulsivity laboratory tasks and the Fear-Conditioning (FC) paradigm of the SR as risk factors for the development of alcohol dependence. Methods The sample included 40 abstinent alcoholic men, who met DSM-IV criteria for Alcohol Dependence and had been abstinent for at least one month. Impulsivity was assessed using two laboratory tests: Stop-Signal Task (SST) and Differential Reinforcement for Low-Rate Responding (DRL6). The FC paradigm of the SR was used as a stress test. Patients were compared to 40 matched controls. Results We found a positive correlation between SST tasks and the FC paradigm of the SR (p Conclusions Impulsivity and stress are significantly correlated in alcohol dependent patients. This means that while healthy subjects cope with stress, alcohol dependent patients react with higher impulsivity when they are exposed to stress situations and this could lead them to drink alcohol to relieve anxiety and depressive symptoms.

Severity of alcohol dependence in the Swedish adult population: Association with consumption and social factors

The severity of alcohol dependence can be estimated by the number of DSM-IV criteria that are fulfilled for this disorder. This paper describes the proportions in a general population sample that meet different numbers of diagnostic criteria for alcohol dependence and their association with drinking and social background factors. Data came from a random, cross-sectional, self-report survey of adults from 12 Swedish communities. 28,800 persons, age 19–70, were surveyed through postal questionnaires. 14,706 questionnaires (51%) could be used for analysis. Alcohol dependence was assessed by questions relating to the seven DSM-IV criteria for alcohol dependence. Alcohol consumption and social background factors were examined in relation to alcohol dependence. A total of 73.8% of the general population fulfilled no criteria for alcohol dependence; 4.0% reported 3 or more criteria and qualified for the diagnosis of alcohol dependence. There were trends toward an increasing number of dependence criteria with increasing consumption levels and negative social background factors. The majority of people with alcohol dependence however did not drink at the highest consumption levels, did not live alone, and were not unemployed. Given the current definition of alcohol dependence the majority of people have few criteria fulfilled (3 or 4) and few social problems. This has important implications for treatment as dependence with low severity may require less treatment and less specialist involvement.

Clinical indices of familial alcohol use disorder.

Alcohol use disorders (AUDs) are clinically heterogeneous and strongly influenced by familial/genetic factors. Can we identify specific clinical features of AUDs that index familial liability to illness? In twins from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders meeting DSM-IV criteria for lifetime AUDs, we examined whether clinical features of AUDs, including individual DSM-IV criteria for alcohol dependence (AD) and alcohol abuse (AA), predicted risk for AUDs in cotwins and/or parents. Analyses of individual criterion were repeated controlling for the total number of endorsed criteria. Across these analyses, examining narrowly and broadly defined AUDs, risk of AUDs in relatives was more consistently predicted by abuse criteria than by dependence criteria, and by criteria reflecting negative psychosocial consequences rather than pharmacologic/biological criteria. Age at onset (AAO) poorly predicted risk in relatives. AUD associated legal problems, the one criterion slated for removal in DSM-5, was the most consistent single predictor of familial risk. Associations observed between individual criteria and risks of illness in relatives were generally stronger in monozygotic than dizygotic twin pairs, suggesting that these symptoms reflect a genetic risk for AUDs. Individual DSM-IV criteria for AA and AD differ meaningfully in the degree to which they reflect the familial/genetic liability to AUDs. Contrary to expectation, the familial/genetic risk to AUDs was better reflected by symptoms of abuse and negative psychosocial consequences of AUD than by early AAO, or symptoms of tolerance and withdrawal.

Impairments of Prepulse Inhibition of the Startle Response in Abstinent Alcoholic Male Patients

Prepulse inhibition (PPI) of the startle reflex, which refers to the ability of innocuous sensory events to reduce the startle reflex, has been described as an operational measure of sensorimotor gating that is reduced in several neuropsychiatric disorders, such as schizophrenia, but experience is lacking in addictions and alcoholism. The aim of this study was to examine the existence of impairments in the startle response and PPI in abstinent alcoholic men. Testing for PPI was conducted on 60 abstinent alcoholic men aged 18-65 years (mean 46.37) who met DSM-IV criteria for alcohol dependence and had been abstinent for more than a month at the time of testing. The comparison group were compared with 37 sex- age- and education-matched controls without alcohol dependence. Magnitudes of the startle reflex were lower in patients than in controls. The differences were statistically significant (P < 0.05) in trials with prepulses presented 30 and 120 ms before the onset of the startle stimulus. There was also a statistically significant (P < 0.05) reduced percentage of PPI when the prepulse was presented 30 ms before the startle stimulus. These data suggest that sensory information processing mechanisms could be damaged in abstinent alcoholic patients. The fact that these findings are common to other psychiatric disorders could indicate the existence of a common vulnerability marker and explain the high degree of comorbidity between alcoholism and other mental illnesses.

Genetic influences on craving for alcohol

IntroductionCraving is being considered for inclusion in the Diagnostic and Statistical Manual (DSM) DSM-5. However, little is known of its genetic underpinnings — specifically, whether genetic influences on craving are distinct from those influencing DSM-IV alcohol dependence. MethodAnalyses were conducted in a sample of unrelated adults ascertained for alcohol dependence (N=3976). Factor analysis was performed to examine how alcohol craving loaded with the existing DSM-IV alcohol dependence criteria. For genetic analyses, we first examined whether genes in the dopamine pathway, including dopamine receptor genes (DRD1, DRD2, DRD3, DRD4) and the dopamine transporter gene (SLC6A3), which have been implicated in neurobiological studies of craving, as well as alpha-synuclein (SNCA), which has been previously found to be associated with craving, were associated with alcohol craving in this sample. Second, in an effort to identify novel genetic variants associated with craving, we conducted a genomewide association study (GWAS). For variants that were implicated in the primary analysis of craving, we conducted additional comparisons — to determine if these variants were uniquely associated with alcohol craving as compared with alcohol dependence. We contrasted our results to those obtained for DSM-IV alcohol dependence, and also compared alcohol dependent individuals without craving to non-dependent individuals who also did not crave alcohol. ResultsTwenty-one percent of the full sample reported craving alcohol. Of those reporting craving, 97.3% met criteria for DSM-IV alcohol dependence with 48% endorsing all 7 dependence criteria. Factor analysis found a high factor loading (0.89) for alcohol craving. When examining genes in the dopamine pathway, single nucleotide polymorphisms (SNPs) in DRD3 and SNCA were associated with craving (p<0.05). There was evidence for association of these SNPs with DSM-IV alcohol dependence (p<0.05) but less evidence for dependence without craving (p>0.05), suggesting that the association was due in part to craving. In the GWAS, the greatest evidence of association with craving was for a SNP in the integrin alpha D (ITGAD) gene on chromosome 7 (rs2454908; p=1.8×10−6). The corresponding p-value for this SNP with DSM-IV alcohol dependence was similar (p=4.0×10−5) but was far less with dependence without craving (p=0.02), again suggesting the association was due to alcohol craving. Adjusting for dependence severity (number of endorsed criteria) attenuated p-values but did not eliminate association. ConclusionsCraving is frequently reported by those who report multiple other alcohol dependence symptoms. We found that genes providing evidence of association with craving were also associated with alcohol dependence; however, these same SNPs were not associated with alcohol dependence in the absence of alcohol craving. These results suggest that there may be unique genetic factors affecting craving among those with alcohol dependence.