Critical thoughts on current rodent models for evaluating potential treatments of alcohol addiction and withdrawal

Despite years of neurobiological research that have helped to identify potential therapeutic targets, we do not have a reliable pharmacological treatment for alcoholism. There are a range of possible explanations for this failure, including arguments that alcoholism is a spectrum disorder and that different population subtypes may respond to different treatments. This view is supported by categorisations such as early- and late-onset alcoholism, whilst multifactorial genetic factors may also alter responsivity to pharmacological agents. Furthermore, experience of alcohol withdrawal may play a role in future drinking in a way that may distinguish alcoholism from other forms of addiction. Additionally, our neurobiological models, based largely upon results from rodent studies, may not mimic specific aspects of the human condition and may reflect different underlying phenomena and biological processes from the clinical pattern. As a result, potential treatments may be targeting inappropriate aspects of alcohol-related behaviours. Instead, we suggest a more profitable approach is (a) to identify well-defined intermediate behavioural phenotypes in human experimental models that reflect defined aspects of the human clinical disorder and (b) to develop animal models that are homologous with those phenotypes in terms of psychological processes and underlying neurobiological mechanisms. This review describes an array of animal models currently used in the addiction field and what they tell us about alcoholism. We will then examine how established pharmacological agents have been developed using only a limited number of these models, before describing some alternative novel approaches to achieving homology between animal and human experimental measures.     

Basal serum cortisol and dexamethasone-induced growth hormone release in the alcohol dependence syndrome

We assessed the basal serum cortisol and the growth hormone (GH) response to dexamethasone in a group of completely detoxified male alcoholics and a group of healthy controls. There was a significant baseline elevation of serum cortisol in the alcoholics relative to the controls, and in the type 2 alcoholics relative to the type 1 alcoholics. There was no difference found in GH response to dexamethasone between the alcoholics and controls or between the types of alcoholics. There was no relationship found between the age of subject, length of abstinence from alcohol or severity of alcohol dependence and GH response. There was a significant relationship between severity of alcohol dependence and type of alcohol abuser. This may indicate a subtle impairment of the HPA in post withdrawal alcoholics, and between types of alcoholics, which does not appear to be at the pituatary or hypothalamic level.     

Exposure to dysfunctional parenting and trauma events and posttraumatic stress profiles among a treatment sample with coexisting depression and alcohol use problems

Introduction and Aims. Trauma exposure (including experiencing dysfunctional parenting when a child) and posttraumatic stress disorder (PTSD) frequently coexist with major depressive disorder (MDD) and alcohol use disorders (AUD), with the impact of this comorbidity usually studied as a dual disorder (i.e. PTSD‐MDD or PTSD‐AUD). This study explores trauma exposure (including to dysfunctional parenting), PTSD symptom severity and PTSD in people seeking treatment for coexisting depressive symptoms and alcohol use problems. Design and Methods. Participants (n = 221) with current depression and alcohol use problems were recruited. Trauma exposure, PTSD symptoms and PTSD were assessed using the Posttraumatic Stress Diagnostic Scale. The Measure of Parenting Style assessed dysfunctional parenting (neglect/over‐control/abuse) experienced as a child. Results. Most participants experienced trauma (71.6%, n = 159), with more than one‐third reaching DSM‐IV criteria for current PTSD (38.0%, n = 84). Unique to this study was that there were no gender differences in rates of trauma exposure, number of traumatic events and PTSD. More severe PTSD symptoms and PTSD were associated with: childhood neglect; earlier depression onset; more severe depression and alcohol problems; and lower general functioning. More severe problems with alcohol were related to Intrusion and Avoidance symptoms, while severe alcohol dependence symptoms were related to hyperarousal. Discussion and Conclusions. PTSD symptoms and PTSD are highly prevalent in those with coexisting depression and alcohol use problems and are associated with a history of childhood neglect and higher levels of comorbidity. Trauma, PTSD symptoms and PTSD should be assessed and addressed among people seeking treatment for coexisting depression and alcohol problems.[Bailey K, Webster R, Baker AL, Kavanagh DJ. Exposure to dysfunctional parenting and trauma events and posttraumatic stress profiles among a treatment sample with coexisting depression and alcohol use problems. Drug Alcohol Rev 2012;31:529–537]     

Co-occurring addictive behaviors: an analysis of risk profiles among university students

Objectives: The first goal of this study was to empirically identify, among university students, groups with varying levels of risk based on indicators of gambling and substance use. The second goal was to compare the identified groups on various demographic characteristics.

Methods: The study comprised of 2139 full-time undergraduate students, representative of university students in Montreal, Canada. A 3-step latent class logistic regression analysis was performed to identify groups and compare them on demographic characteristics.

Results: The statistical fit indices of the latent class analysis revealed a four-class solution. Class 1 (30.1% of the sample) included non-gamblers with low probabilities of substance use. Class 2 (11.2% of the sample) grouped non-gamblers with high-risk patterns of consumption. Class 3 (36.42% of the sample) included gamblers who are low-risk substance users, and individuals in Class 4 (22.25% of the sample) reported risky patterns of gambling and substance-using behaviors. Results of the logistic regression suggested that gender, being born in Canada, and working full- or part-time are significant predictors of class membership. Participants in both groups labeled at-risk (with and without gambling) were also more likely to report psychological distress and to live outside the family environment.

Conclusions: This study raises important questions regarding the choice of preventive models and feeds into the long-standing debate around universal versus high-risk approaches.     

A typology of families with parental alcohol or drug abuse

Objectives To estimate the prevalence of parental alcohol abuse (PAA) or parental drug abuse (PDA), to compare families with PAA/PDA to non-PAA/PDA families, and to identify different types of families with PAA/PDA in terms of mental disorders in parents, family separation, financial difficulties and educational level. Methods Register-based data from a complete birth cohort of children born in 1991 in Finland (N?=?62,751), and their biological parents. Data were derived from Finnish administrative registers from 1991 to 2009. Latent class analysis was used to construct typology of families with PAA/PDA. Results 10.5% of families were affected by PAA or PDA before the children’s 18th birthday. Of these families, five family types were identified. The most common type was characterised by father’s alcohol abuse but had no other detectable problems besides parental separation. The second type was a family where the father had a drinking or drug problem, had financial difficulties and had moved away from the family’s home. The two less common family types were characterised by the mother’s drinking or drug abuse and mental disorders. The mothers of these family types were rather commonly living with their children. In the fifth family type, child typically did not live with either of the parents, both parents had alcohol/drug abuse and accumulated problems. Conclusions Early prevention and treatment are needed to avoid the accumulation of parental problems in PAA/PDA families. As both biological parents rather rarely were substance abusers, the parental role of the non-substance abusing parent should be supported and strengthened.     

Contemporary alcohol use patterns among a national sample of U.S. adult drinkers

The aim of the current article is to identify subgroups of adult drinkers characterized by typical drinking patterns. Data from the National Epidemiologic Survey on Alcohol and Related Conditions-III were used to classify drinkers based on several indicators of drinking. Past-year drinkers aged 18–64 were included (n = 22,776). Latent class analysis revealed a 5-class model: Occasional, Light Drinkers (28%), Frequent Drinkers (25%), Infrequent Drinkers with Occasional Binging (5%), Frequent Drinkers with Occasional Binging (22%), and High-Intensity Drinkers (20%). Although most were Light Drinkers, many engaged in excessive drinking. Given the potential risk for harm, prevention efforts are warranted particularly for High-Intensity Drinkers.     

Do Classes of Polysubstance Use in Adolescence Differentiate Growth in Substances Used in the Transition to Young Adulthood?

Background: Past studies have differentiated classes of polysubstance use in adolescence, however, the associations of adolescent polysubstance use classes with longitudinal substance use trajectories from adolescence to young adulthood have not been studied. Objective: The current study examined substance use classes during adolescence and longitudinal trajectories of each substance used across the transition to young adulthood. Method: Data were collected biennially from 662 youth and followed 10 years across six measurement assessments. Using baseline data (T1), latent class analysis was used to identify classes of polysubstance use (cigarette, alcohol, marijuana, and illicit drug use) during adolescence. Using T2 through T6 data, we fit latent growth models for cigarette, alcohol, marijuana, and illicit drug use to examine longitudinal trajectories of each substance used by class. Results: A three-class model fit the data best and included a poly-use class, that had high probabilities of use among all substances, a co-use class, that had high probabilities of use among alcohol and marijuana, and a low-use class that had low probabilities of use among all substances. We then examined trajectories of each substance used by class. Strong continuity of substance use was found by class across 14 years. Additionally, for some substances, higher average levels of use of at age 14 were associated with change in growth of other substances used over time. Conclusions/Importance: Efforts that only target a single drug type may be missing an important opportunity to reduce the use and subsequent consequences related to the use of multiple substances.     

A comparative latent class analysis of endorsement profiles of DSM-IV diagnostic criteria for problem gambling among adolescents from a community and a treatment sample

The DSM-IV approach to gambling taxonomy is predicated upon the number of diagnostic criteria with little regard for the nature of the specific items. This study examined the variation in gambling pathology that might exist due to the specific pattern of DSM-IV criteria endorsement, these differences between genders, and in the presence of prior addictions. The likelihood of item endorsement for the DSM-IV criteria for males and females in a community and a treatment sample of adolescents with known prior history of substance abuse was examined. A significant gender effect was found for several DSM-IV items in the community sample but not in the treatment sample. Latent class analyses identified different subtypes or classes of endorsement patterns of DSM-IV gambling criteria in adolescents which differed according to whether we looked at males or females in a community sample of adolescents or at a group of treatment adolescents. The results suggest that there may be a divergence in the pathways that male and female adolescent gamblers negotiate depending on the nature of their gambling behaviours. There seems to be a pathway with physiological components and a separate pathway involving antisocial behaviours. Furthermore, male and female adolescent gamblers with prior addictions have a pattern of gambling behaviours in which the vulnerability to gambling problems is more likely to involve behaviours with physiological or neuroadaptive components than antisocial behaviours and this vulnerability is particularly acute for female substance-dependent gamblers where the development of tolerance plays an especially important role.     

Patterns of alcohol use among men receiving treatment for heroin and/or cocaine use in England,Brazil and Spain. A cross-country analysis

Abstract

Introduction: Although alcohol is widely used concurrently with illicit drugs, the role of alcohol in recovery from and relapse to drug use is under-researched. This study investigates drinking patterns and factors associated with harmful drinking among men receiving community treatment for heroin and/or cocaine use.

Methods: Secondary analysis of 3 cross-sectional studies in England (n?=?153), Brazil (n?=?149) and Spain (n?=?131) was conducted. Sociodemographic, alcohol consumption (AUDIT), substance use, treatment characteristics, and physical health were assessed. Logistic regression determined factors associated with harmful drinking.

Results: 41% of men receiving heroin and/or cocaine treatment met criteria for harmful drinking. Of this, 28% were not receiving treatment for alcohol. Factors identified with harmful drinking among those who were not receiving treatment for alcohol use were as follows: homeless, unemployment/receiving benefits, poly drug use, history of injecting drug(s), hepatitis C seropositive, and receiving treatment for heroin use with/without treatment for cocaine use. Participants from England who met criteria for harmful drinking were more likely to report not receiving treatment for alcohol use than those from Brazil and Spain.

Discussion: Findings show that harmful drinking is common among men in treatment for drug use and remains neglected by the services.     

Latent developmental trajectories of episodic heavy drinking from adolescence to early adulthood: Predictors of trajectory groups and alcohol problems in early adulthood as outcome

Introduction and Aims. To identify latent developmental episodic heavy drinking (EHD) trajectory groups for Norwegian adolescents, investigate risk factors associated with group membership and to assess differences in alcohol problems between different groups in early adulthood. Design and Methods. Data were from 1266 individuals measured at four time points from age 13/14 years to age 26/27 years. Latent class growth analysis was used to identify groups with different EHD development. Multinomial logistic regression was used to investigated if gender, impulsivity, school commitment, parents' socio‐economic status, frequency of seeing parents drunk and parental knowledge could predict group membership. Differences in alcohol problem scores at age 26/27 were also assessed. Results. Four trajectory groups were identified: ‘stable high’, ‘early increasers’, ‘late increasers’ and ‘stable low’. Membership of the high‐risk trajectory groups ‘stable high’ and ‘early increasers’ was predicted by high impulsivity, low school commitment, high frequency of seeing parents drunk and low parental knowledge. The risk of alcohol problems at age 26/27 was greater for the ‘stable high’ group, the ‘early increasers’ and the ‘late increasers’ compared with the ‘stable low’ group. The ‘stable high’ and ‘early increasers’ had similar risk of alcohol problems. Discussion and Conclusions. Stable high and early increasing EHD in adolescence was associated with more alcohol problems in early adulthood. Such trajectories were predicted by high impulsivity, low school commitment, high frequency of seeing parents drunk and low parental knowledge. [Brunborg GS, Norström T, Storvoll EE. Latent developmental trajectories of episodic heavy drinking from adolescence to early adulthood: Predictors of trajectory groups and alcohol problems in early adulthood as outcome.     

Drunken driving and riding with a drunken driver: adolescent types at higher risk

Abstract

The leading cause of death of adolescents in developed countries is injury. Alcohol is a major contributor to adolescent injury. Most of the injury deaths in youth are caused by traffic crashes. Driving under the influence (DUI) and riding with a driver who is under the influence (RUI) of alcohol increase the risk of road crash. The focus of this study is how adolescents’ risk of DUI and RUI differ in relation to their experience of parental control and peer pressure to substance use, other risky behaviours and leisure time activities. The analyses are based on data from the European School Survey Project on Alcohol and Other Drugs collected from 15- to 16-year-old Finnish adolescents in 2015 (n?=?4049, response rate 88.7%). The study shows that problems tend to entangle in some adolescent groups in which DUI and RUI are also more common. Adolescents with higher probability of using various substances, of starting alcohol use at young age, of experiencing weak parental control, and high peer pressure are at higher risk of DUI and RUI. The results indicate that professionals and authorities handling underage DUI and RUI ought to consider adolescents’ situation as a whole.     

Hazardous alcohol consumption and other barriers to antiviral treatment among hepatitis C positive people receiving opioid maintenance treatment

Amongst people on opioid maintenance treatment (OMT), chronic hepatitis C (HCV) is common but infrequently treated. Numerous barriers, including misuse of alcohol may limit efforts at anti-viral treatment. The aim of this study was to define barriers, including alcohol misuse, to the effective treatment of HCV amongst OMT recipients. Ninety-four OMT patients completed the 3-item Alcohol Use Disorders Identification Test (AUDIT-C). A semi-structured interview was used in 53 subjects to assess alcohol use in detail, psychological health, discrimination and access to HCV treatment. Feasibility of brief intervention for alcohol misuse was assessed. Of the screening participants, 73% reported they were HCV positive. Of the detailed interview participants, 26% reported no drinking in the past month, but 53% scored 8 or more on AUDIT and 42% exceeded NHMRC drinking guidelines. Twenty subjects received brief intervention and among 17 re-interviewed at one month, alcohol consumption fell by 3.1 g/day (p = 0.003). Severe or extremely severe depression, stress and anxiety were found in 57%, 51% and 40% of interviewees respectively. Episodic heavy drinking, mental health problems, perceived discrimination, limited knowledge concerning HCV were all common and uptake of HCV treatment was poor. Brief intervention for alcohol use problems was acceptable to OMT patients, and warrants further study. [Watson B, Conigrave KM, Wallace C, Whitfield JB, Wurst F, Haber PS. Hazardous alcohol consumption and other barriers to antiviral treatment among hepatitis C positive people receiving opioid maintenance treatment. Drug Alcohol Rev 2007;26:]     

Alcohol screening and alcohol interventions among patients with hypertension in primary health care: an empirical survey of German general practitioners

Background: Alcohol is one of the least intervened risk factors in the management of hypertension at the primary care level. In order to improve alcohol interventions, a better understanding of knowledge, attitudes and clinical practice of lifestyle interventions in the management of hypertension is needed.

Method: As a part of a European study (France, Germany, Italy, Spain, UK), 211 German general practitioners (GPs) were recruited in Bavaria and Hamburg and surveyed via an Internet-based questionnaire. Results were compared with the European sample (n?=?2870).

Results: One-third of the patients seen by German GPs had hypertension (36.2%, standard deviation (SD): 14.6) and among cases with hypertension, less than half were ever screened for alcohol (4.5 out of 10 patients). The foremost reasons for not screening for alcohol were that alcohol was not considered a major risk factor for hypertension plus the lack of knowledge of appropriate alcohol screening instruments. The majority of German GPs managed patients with hazardous drinking levels themselves or in their practice (71.3%, 95% confidence interval (CI): 64.6–77.2%), but only 42.0% (95% CI: 35.2–49.0%) managed alcohol dependent patients. German screening rates were slightly lower but interventions of screened positive patients higher than the European average.

Conclusions: Rates of alcohol screening in patients with hypertension in primary health care may be increased by improving GPs knowledge of alcohol as a major risk factor for hypertension, increasing GPs education on alcohol and screening instruments, and providing reimbursement. This may increase treatment of alcohol problems in patients with hypertension and reduce hypertension.     

Stimulant use trajectories and the longitudinal risk of heavy drinking: findings from a rural population-based study

The extant literature offers little information about the longitudinal course of alcohol use among stimulant users, particularly those in rural areas, but it is plausible that reductions in stimulant use are accompanied by increases in heavy drinking. The objective of this study was to examine the longitudinal relationships between heavy drinking days and latent trajectories of powder cocaine, crack cocaine, and methamphetamine use. Participants (n = 710) were identified via Respondent-Driven Sampling in 3 rural communities in each of 3 states, with interviews conducted every 6 months over 3 years. Latent trajectory classes for powder cocaine, crack cocaine, and methamphetamine use were identified by conducting latent class growth analysis (LCGA). Generalized linear models (GLM) were conducted to examine how these latent classes were associated with the number of heavy drinking days in the past 30 days. Heavy drinking days did not significantly change over time when adjusting for covariates. Compared to those with a “fast low” trajectory of crack use, those with “steady high” and “declining” trajectories had more heavy drinking days. Compared to those with a “fast low” trajectory of powder cocaine use, those with a “steady moderate” trajectory had more heavy drinking days. Trajectories of methamphetamine use were not significantly associated with heavy drinking days. In conclusion, heavy alcohol use changes little over time among rural stimulant users. Many rural cocaine users could potentially benefit from interventions aimed at curtailing heavy drinking.     

The Role of Individual and Contextual Factors in Differentiating Substance Use Profiles among Adolescents

Background: Adolescent substance use is a significant public health concern due to its prevalence and associated negative consequences. Although many adolescents use substances, there is substantial heterogeneity in their use patterns. Identifying risk and protective factors that differentiate adolescents with different substance use profiles is important for preventing negative consequences for those at risk. Objective: This study identified distinct latent profiles of substance use by considering adolescents' involvement in multiple common and illicit substances as well as related problems and examined the extent to which individual and contextual factors in the family, peer, school, and neighborhood environments were related to adolescents' membership of substance use profiles. Method: Data came from 9,155 high school students (51% female; 74% European American) who completed electronic surveys in the 2009 Dane County Youth Assessment (DCYA). Latent class analysis (LCA) was conducted to identify profiles of adolescent substance involvement and related problems. Multinomial logistic regression was conducted to examine associations between individual and contextual factors and latent class membership. Results: LCA identified four distinct profiles of adolescent substance use characterized by both licit and illicit substance use and related problems: Abstainers (56.3%), Alcohol-only users (25.6%), Alcohol-cigarette-marijuana users (13.8%), and Problem polysubstance users (4.3%). Controlling for demographics, individual and contextual factors were associated with adolescents' likelihoods of membership in substance use profiles; notably, the associations varied to some extent across substance use profiles. Conclusions: Substance use is heterogeneous among adolescents. Effects of risk and protective factors on substance use vary depending on adolescents' substance use patterns.     

Understanding the hangover experience in Canadian adults: A latent class analysis of hangover symptom patterns and their alcohol-related correlates

Aim: Given the ubiquitous nature of hangover experience among drinkers, this study aimed to profile hangover experience in terms of the number and patterns of past year symptoms. Methods: Current drinkers in Canada (n?=?565) recruited through zoompanel were asked about 13 past year hangover symptoms. These were explored through correlation with alcohol consumption, problems, treatment and other factors. Findings: Increased number of symptoms were associated with higher Alcohol Use Disorders Identification Test (AUDIT) problem score, perceived harm from drinking, younger age and flushing/blushing when drinking (Mean = 3.3 symptoms). Four patterns were found from latent class analysis; class 4 (43%) no symptoms; class 3 (13%) thirst, tiredness, headache, nausea and vomiting; class 2 (22%) thirst, tiredness and headache; and class 1 (21%) wide range. Class 1 was characterised by blushing when drinking, higher perceived harm and attempts to reduce drinking due to hangovers. Classes 1–3 were associated with heavier consumption; only class 3 compared with class 4 had lower drinking refusal self-efficacy. Conclusions: higher alcohol consumption and lower drinking refusal self-efficacy relate to more symptoms; however, a group with variable alcohol consumption did not experience hangovers. The link between problems, treatment and hangover was not clear from patterns of symptoms; symptom severity may be worth further investigation.     

Gender,intoxication and the developing brain: Problematisations of drinking among young adults in Australian alcohol policy

In this article, we draw on recent scholarly work in the poststructuralist analysis of policy to consider how policy itself functions as a key site in the constitution of alcohol ‘problems’, and the political implications of these problematisations. We do this by examining Australian alcohol policy as it relates to young adults (18–24 years old). Our critical analysis focuses on three national alcohol policies (1990, 2001 and 2006) and two Victorian state alcohol policies (2008 and 2013), which together span a 25-year period. We argue that Australian alcohol policies have conspicuously ignored young adult men, despite their ongoing over-representation in the statistical ‘evidence base’ on alcohol-related harm, while increasingly problematising alcohol consumption amongst other population subgroups. We also identify the development of a new problem representation in Australian alcohol policy, that of ‘intoxication’ as the leading cause of alcohol-related harm and rising hospital admissions, and argue that changes in the classification and diagnosis of intoxication may have contributed to its prioritisation and problematisation in alcohol policy at the expense of other forms of harm. Finally, we draw attention to how preliminary and inconclusive research on the purported association between binge drinking and brain development in those under 25 years old has been mobilised prematurely to support calls to increase the legal purchasing age from 18 to 21 years. Our critical analysis of the treatment of these three issues – gender, intoxication, and brain development – is intended to highlight the ways in which policy functions as a key site in the constitution of alcohol ‘problems’.     

Alcohol and Drug Use,Pain and Psychiatric Symptoms among Adults Seeking Outpatient Psychiatric Treatment: Latent Class Patterns and Relationship to Health Status

Background: Substance use, psychiatric problems, and pain frequently co-occur, yet clinical profiles of treatment-seeking patients are poorly understood. To inform service and treatment planning, substance use and symptom patterns were examined in an outpatient psychiatry clinic, along with the relationship of these patterns to demographic characteristics and physical health. Methods: Patients (N = 405; age M = 38; 69% White; 60% female) presenting for intake in a psychiatry outpatient clinic completed a computerized assessment of psychiatric problems, drinking, and drug use. Substance use and psychiatric symptom patterns among the sample were identified using latent class analysis. Results: A 4-class model fit the data best: Class (1) Moderate symptoms/wide-range users (22.0%) had moderate depression and panic; tobacco, cocaine, hallucinogen, and ecstasy use; and high cannabis use. Class (2) Moderate depression/panic (37.8%) had moderate depression and panic. Class (3) Depression/anxiety, tobacco, and cannabis users (28.0%) had high depression, obsessions, and panic, and moderate pain severity, social phobia, compulsions, trauma, tobacco, and cannabis use. Class (4) Severe/wide range symptoms/users (12.0%) had high panic, depression, social phobia, obsessions, drug use, and moderate pain. Gender, ethnicity, and health status varied by class. Conclusions: Findings highlight the preponderance of substance use (particularly cannabis) and its relationship to psychiatric symptom severity, pain, and health status among those presenting for mental health treatment.