Aspects Of Alcohol Use Disorder Research Articles

Targeting muscarinic receptors for the treatment of alcohol use disorders: Opportunities and hurdles for clinical development.

Emerging evidence suggests muscarinic acetylcholine receptors represent novel targets to treat alcohol use disorder. In this review, we draw from literature across medicinal chemistry, molecular biology, addiction and learning/cognition fields to interrogate the proposition for muscarinic receptor ligands in treating various aspects of alcohol use disorder, including cognitive dysfunction, motivation to consume alcohol and relapse. In support of this proposition, we describe cholinergic dysfunction in the pathophysiology of alcohol use disorder at a network level, including alcohol-induced adaptations present in both human post-mortem brains and reverse-translated rodent models. Preclinical behavioural pharmacology implicates specific muscarinic receptors, in particular, M4 and M5 receptors, as potential therapeutic targets worthy of further interrogation. We detail how these receptors can be selectively targeted in vivo by the use of subtype-selective allosteric modulators, a strategy that overcomes the issue of targeting a highly conserved orthosteric site bound by acetylcholine. Finally, we highlight the intense pharma interest in allosteric modulators of muscarinic receptors for other indications that provide an opportunity for repurposing into the alcohol use disorder space and provide some currently unanswered questions as a roadmap for future investigation.

Voluntary and forced exposure to ethanol vapor produces similar escalation of alcohol drinking but differential recruitment of brain regions related to stress, habit, and reward in male rats

A major limitation of the most widely used current animal models of alcohol dependence is that they use forced exposure to ethanol including ethanol-containing liquid diet and chronic intermittent ethanol (CIE) vapor to produce clinically relevant blood alcohol levels (BAL) and addiction-like behaviors. We recently developed a novel animal model of voluntary induction of alcohol dependence using ethanol vapor self-administration (EVSA). However, it is unknown whether EVSA leads to an escalation of alcohol drinking per se, and whether such escalation is associated with neuroadaptations in brain regions related to stress, reward, and habit. To address these issues, we compared the levels of alcohol drinking during withdrawal between rats passively exposed to alcohol (CIE) or voluntarily exposed to EVSA and measured the number of Fos+ neurons during acute withdrawal (16 h) in key brain regions important for stress, reward, and habit-related processes. CIE and EVSA rats exhibited similar BAL and similar escalation of alcohol drinking and motivation for alcohol during withdrawal. Acute withdrawal from EVSA and CIE recruited a similar number of Fos+ neurons in the Central Amygdala (CeA), however, acute withdrawal from EVSA recruited a higher number of Fos+ neurons in every other brain region analyzed compared to acute withdrawal from CIE. In summary, while the behavioral measures of alcohol dependence between the voluntary (EVSA) and passive (CIE) model were similar, the recruitment of neuronal ensembles during acute withdrawal was very different. The EVSA model may be particularly useful to unveil the neuronal networks and pharmacology responsible for the voluntary induction and maintenance of alcohol dependence and may improve translational studies by providing preclinical researchers with an animal model that highlights the volitional aspects of alcohol use disorder.

Trauma Cue-Elicited Alcohol Craving as a Function of Adult Versus Childhood-Onset Interpersonal Traumatic Events in Young Adult Drinkers.

Childhood trauma may influence risk for alcohol use disorder and posttraumatic stress disorder through negative and positive reinforcement drinking. Laboratory studies evaluating childhood trauma in relation to these phenotypes are limited. This study examined the influence of childhood index traumas on responses to trauma and alcohol cues among 184 college students (50.0% female) endorsing lifetime interpersonal trauma and current weekly alcohol use. Participants' subjective alcohol craving and distress were measured in response to four narrative (trauma vs. neutral) and beverage (alcohol vs. water) cue combinations. Forward-fitted linear mixed-effects models indicated main effects of childhood index traumas on distress (β= 6.151, p = .001) and craving (β = 0.656, p = .023), wherein individuals with childhood index traumas showed evidence of elevated levels of distress and craving. Childhood index trauma interacted with the narrative cue to predict distress (β = -10.764, p = .002), wherein individuals with childhood index traumas showed greater levels of distress to the neutral cue, and individuals with adult index traumas showed greater levels of distress to the trauma cue. Childhood index trauma interacted with the beverage cue to predict craving (β = -0.599, p = .011), wherein childhood index traumas were associated with greater levels of craving to neutral cues. Childhood index trauma did not significantly interact with the beverage cue to predict distress or the narrative cue to predict craving (ps > .05). Childhood trauma may be more relevant to positive rather than negative reinforcement aspects of alcohol use disorder during young adulthood.

The effects of nalmefene on the impulsive and reflective system in alcohol use disorder: A resting-state fMRI study

RationaleCentral aspects of alcohol use disorder (AUD) are the irresistible desire for alcohol and impaired control over its intake. According to the triadic neurocognitive model of addiction, this arises from aberrant functioning of different neural and cognitive systems: an impulsive system, a reflective system, and the abnormal dynamics between both systems based on an insular-dependent system.ObjectivesIn this study, we examined the effects of a single dose of nalmefene on resting-state functional connectivity (rsFC) patterns within and between these addiction-related neural systems in AUD.MethodsNon-treatment seeking participants with AUD (N = 17; 19–66 years, 6 female) took part in a randomized, placebo-controlled, double-blind, crossover study and received either a single dose of 18 mg nalmefene or a placebo. Using seed-based correlation analyses on resting‐state functional magnetic resonance imaging data, we examined the effects of nalmefene on key nodes related to the (1) impulsive system; (2) reflective system; (3) salience network; and (4) default mode network.ResultsUnder nalmefene, participants showed reduced rsFC between components of the impulsive system (Nucleus accumbens–putamen/pallidum/insula). Reduced rsFC was found between elements of the reflective system and impulsive system (orbitofrontal cortex–insula/putamen/pallidum), salience network (orbitofrontal cortex–insula/inferior frontal gyrus), and default mode network (lateral prefrontal cortex–precuneus/cuneus). Components of the salience network showed both increased (anterior cingulate cortex) and decreased (insular cortex) rsFC to elements of the reflective system.ConclusionA single dose of nalmefene impacts rsFC and alters the interaction between key nodes of addiction-related neural systems in non-treatment seeking participants with AUD. Nalmefene may normalize rsFC patterns by weakening the impulsive system while strengthening the reflective system.Trial registration: clinicaltrials.gov: NCT02372318.

Involvement of the Dorsal Vagal Complex in Alcohol-Related Behaviors

The neurobiological mechanisms that regulate the development and maintenance of alcohol use disorder (AUD) are complex and involve a wide variety of within and between systems neuroadaptations. While classic reward, preoccupation, and withdrawal neurocircuits have been heavily studied in terms of AUD, viable treatment targets from this established literature have not proven clinically effective as of yet. Therefore, examination of additional neurocircuitries not classically studied in the context of AUD may provide novel therapeutic targets. Recent studies demonstrate that various neuropeptides systems are important modulators of alcohol reward, seeking, and intake behaviors. This includes neurocircuitry within the dorsal vagal complex (DVC), which is involved in the control of the autonomic nervous system, control of intake of natural rewards like food, and acts as a relay of interoceptive sensory information via interactions of numerous gut-brain peptides and neurotransmitter systems with DVC projections to central and peripheral targets. DVC neuron subtypes produce a variety of neuropeptides and transmitters and project to target brain regions critical for reward such as the mesolimbic dopamine system as well as other limbic areas important for the negative reinforcing and aversive properties of alcohol withdrawal such as the extended amygdala. This suggests the DVC may play a role in the modulation of various aspects of AUD. This review summarizes the current literature on neurotransmitters and neuropeptides systems in the DVC (e.g., norepinephrine, glucagon-like peptide 1, neurotensin, cholecystokinin, thyrotropin-releasing hormone), and their potential relevance to alcohol-related behaviors in humans and rodent models for AUD research. A better understanding of the role of the DVC in modulating alcohol related behaviors may lead to the elucidation of novel therapeutic targets for drug development in AUD.

Astrocytes play a critical role in mediating the effect of acute ethanol on central amygdala glutamatergic transmission

The Central Amygdala (CeA) has been heavily implicated in many aspects of alcohol use disorder. Ethanol (EtOH) has been shown to modulate glutamatergic transmission in the lateral subdivision of the CeA, however, the exact mechanism of this modulation is still unclear. EtOH exposure is associated with increased pro-inflammatory cytokines in the CeA, and inhibition of neuroimmune cells (microglia and astrocytes) has previously been shown to reduce EtOH drinking in animal models. Since neuroimmune activation seems to be involved in many of the effects of EtOH, we hypothesized that acute EtOH exposure will increase excitatory glutamatergic transmission in the CeA via modulation of neuroimmune cells. Using ex vivo brain slice whole-cell patch clamp electrophysiology, it was found that a physiologically relevant concentration of EtOH (20 mM) significantly increased presynaptic glutamatergic transmission in the CeA. Pharmacologic and chemogenetic inhibition of astrocyte function significantly reduced the ability of EtOH to modulate CeA glutamatergic transmission with minimal impact of microglia inhibition. This finding prompted additional studies examining whether direct neuroimmune activation through lipopolysaccharide (LPS) might lead to an increase in the glutamatergic transmission in the CeA. It was found that LPS modulation of glutamatergic transmission was limited by microglia activation and required astrocyte signaling. Taken together these results support the hypothesis that acute EtOH enhances lateral CeA glutamatergic transmission through an astrocyte mediated mechanism.This article is part of the special Issue on ‘Neurocircuitry Modulating Drug and Alcohol Abuse'.

Reinforcement-based cognitive biases as vulnerability factors in alcohol addiction: From humans to animal models.

Alcohol use disorder (AUD) is one of the most common, but still poorly treated, psychiatric conditions. Developing new treatments requires a better understanding of the aetiology of symptoms and evaluation of novel therapeutic targets in preclinical studies. Recent developments in our understanding of the reinforcement-based cognitive biases (RBCBs) that contribute to the development of AUD and its treatment offer new opportunities for both clinical and preclinical research. In this review, we first briefly describe psychological and cognitive theories that involve various aspects of reinforcement sensitivity in the development, maintenance, and recurrence of alcohol addiction. Furthermore, in separate sections, we describe studies investigating RBCBs and their neural, neurochemical, and pharmacological correlates, and we discuss possible interactions between RBCBs and trajectories of AUD. Finally, we describe how recent translational studies using state-of-the-art animal models can facilitate our understanding of the role of reinforcement sensitivity and RBCBs in various aspects of AUD. LINKED ARTICLES: This article is part of a themed issue on New discoveries and perspectives in mental and pain disorders. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.17/issuetoc.

Sobering centers, emergency medical services, and emergency departments: A review of the literature.

Acute alcohol intoxication accounts for a large proportion of potentially unnecessary emergency department visits and expenditure. Sobering centers are a cheaper alternative treatment option for alcohol intoxication and can provide an opportunity to treat the psychosocial aspects of alcohol use disorder. The objective of this review is to analyze the existing literature regarding the use of sobering centers, EMS and their role in transporting to sobering centers, and the appropriate triage of the intoxicated patient. Excessive alcohol consumption accounts for an estimated $24.6 billion in healthcare costs and patients are often referred to the emergency department for expensive care. Current literature suggests sobering centers are an alternative to acute hospitalization and are safe, relatively inexpensive, and may facilitate more aggressive connection to resources such as longitudinal rehabilitation programs for the acutely intoxicated patient. EMS plays a pivotal role in triage and transportation of intoxicated individuals, but demonstration of outcomes in lacking. Sobering centers are a cost effective alternative to emergency department visits for acute alcohol intoxication and further research is required to identify safe, effective protocols for EMS to triage patients to appropriate treatment destinations.

Discriminative Stimulus Effects and Metabolism of Ethanol in Rhesus Monkeys.

Animal models are an essential feature of drug and pharmacotherapy development for treating alcohol use disorders (AUDs). The rhesus macaque is a robust animal model for many aspects of AUDs particularly in exploiting individual differences in oral self-administration of ethanol (EtOH), endocrine orchestration of stress response, and menstrual cycle characteristics. However, the clearance rates of EtOH have not been reported in this species, and the GABAA and N-methyl-D-aspartate (NMDA) receptor involvement in EtOH's discriminative stimulus effects has not been fully characterized. EtOH clearance rates following 2 doses of EtOH on separate days (0.5 and 1.0g/kg, i.g.) were determined in 8 young adult male rhesus macaques. The EtOH was given by nasogastric gavage, and repeated blood samples were taken over 5hours without sedation. Next, all subjects were trained on a 2-choice 1.0g/kg EtOH (i.g.) versus water discrimination with a 60-minutes pretreatment period to capture peak blood EtOH concentration (BEC). Substitution testing was conducted with GABAA ligands pentobarbital (i.g. and i.m.) and midazolam (i.g.), as well as NMDA antagonist MK-801 (i.m.). Peak BECs were 34 and 87mg/dl for 0.5 and 1.0g/kg doses, respectively, and occurred at 66 and 87minutes following gavage. All GABAA and NMDA ligands tested resulted in responding on the EtOH-appropriate lever with the potency ranking of MK-801 (ED50 : 0.017mg/kg)>midazolam (ED50 : 1.6mg/kg)>pentobarbital (ED50 : 3.7mg/kg)>EtOH (ED50 : 700mg/kg, or 0.7g/kg) in these subjects. These results suggest that the compound discriminative stimulus effects of EtOH are highly consistent across species, providing further support for the rhesus macaque as strong model for pharmacotherapy development for AUD.

A sleeping giant: Suvorexant for the treatment of alcohol use disorder?

There are currently 3 FDA approved treatments for alcohol use disorder (AUD) in the USA, opioid receptor antagonists such as naltrexone, disulfiram and acamprosate. To date, these have been largely inadequate at preventing relapse at a population level and this may be because they only target certain aspects of AUD. Recently, suvorexant, a dual orexin receptor antagonist, has been FDA approved for the treatment of insomnia. Importantly, sleep disruptions occur during both acute and prolonged alcohol exposure and sleep deprivation is a potent factor promoting relapse to alcohol use. In this mini review article, we explore the therapeutic potential of suvorexant for the treatment of AUD. In particular, we highlight that in addition to altering the motivational properties of alcohol, suvorexant may also address key physiological components associated with alcohol withdrawal and abstinence, such as sleep disruptions, which should in turn help reduce or prevent relapse.

Advances in behavioral animal models of alcohol use disorder.

Alcohol use disorder (AUD) is a multifaceted neuropsychiatric disease that combines behavioral, psychosocial, and neurobiological aspects. Over the previous decade, animal models have advanced in modeling the major psychological constructs that characterize AUD. These advances pave the road for more sophisticated behavioral models that capture addiction-related aspects, such as alcohol craving, compulsive seeking and intake, dependence, and relapse. In this review, we survey the recent progress in behavioral animal modeling of five aspects of AUD: alcohol consumption, dependence, and seeking; compulsivity in alcohol intake despite adverse outcomes; vulnerability and resilience factors in alcohol addiction; relapse despite treatment; and relapse prevention by manipulating alcohol-associated memory reconsolidation. These advances represent a general attempt to grasp the complexity and multidimensional nature of AUD, and to focus on behavioral characteristics that better reflect and model this disorder.

Molecular mechanisms underlying striatal synaptic plasticity: relevance to chronic alcohol consumption and seeking.

The striatum, the input structure of the basal ganglia, is a major site of learning and memory for goal-directed actions and habit formation. Spiny projection neurons of the striatum integrate cortical, thalamic, and nigral inputs to learn associations, with cortico-striatal synaptic plasticity as a learning mechanism. Signaling molecules implicated in synaptic plasticity are altered in alcohol withdrawal, which may contribute to overly strong learning and increased alcohol seeking and consumption. To understand how interactions among signaling molecules produce synaptic plasticity, we implemented a mechanistic model of signaling pathways activated by dopamine D1 receptors, acetylcholine receptors, and glutamate. We use our novel, computationally efficient simulator, NeuroRD, to simulate stochastic interactions both within and between dendritic spines. Dopamine release during theta burst and 20-Hz stimulation was extrapolated from fast-scan cyclic voltammetry data collected in mouse striatal slices. Our results show that the combined activity of several key plasticity molecules correctly predicts the occurrence of either LTP, LTD, or no plasticity for numerous experimental protocols. To investigate spatial interactions, we stimulate two spines, either adjacent or separated on a 20-μm dendritic segment. Our results show that molecules underlying LTP exhibit spatial specificity, whereas 2-arachidonoylglycerol exhibits a spatially diffuse elevation. We also implement changes in NMDA receptors, adenylyl cyclase, and G protein signaling that have been measured following chronic alcohol treatment. Simulations under these conditions suggest that the molecular changes can predict changes in synaptic plasticity, thereby accounting for some aspects of alcohol use disorder.

Aspects of alcohol use disorder affecting social cognition as assessed using the Mini Social and Emotional Assessment (mini-SEA)

BackgroundAlcohol Use Disorder (AUD) is associated with problems with processing complex social scenarios. Little is known about the relationship between distinct AUD-related factors (e.g., years of problematic drinking), aspects of cognitive function and dysfunction in individuals diagnosed with AUD, and the relative impact these may have on social cognition. AimsTo explore differences in social cognition between a group of participants diagnosed with AUD and controls, using a clinical measure, the Mini Social and Emotional Assessment (mini-SEA). The mini-SEA was used to evaluate social and emotional understanding through a facial emotional recognition task and by utilising a series of social scenes some of which contain a faux pas (social error). MethodsEighty-five participants (individuals with AUD and controls) completed demographic questions and a general cognitive and social cognitive test battery over three consecutive days. ResultsBetween group analyses revealed that the participants with AUD performed less well on the faux pas test, and differences were also revealed in the emotional facial recognition task. Years of problematic alcohol consumption was the strongest predictor of poor ToM reasoning. ConclusionThese results suggest a strong link between AUD chronicity and social cognition, though the direction of this relationship needs further elucidation. This may be of clinical relevance to abstinence and relapse management, as basic social cognition skills and ability to maintain interpersonal relationships are likely to be crucial to recovery.

A study to assess the knowledge of psychiatric aspects of alcohol use disorders in medical students

Aims and Objectives: The aim of this study was to assess the knowledge of psychiatric aspects of alcohol use disorders (AUDs) in medical students. Materials and Methods: A cross-sectional study conducted in Mamata Medical College, Khammam, Telangana, from June 2014 to May 2015. The study sample consisted of 180 medical students (115 final year and 65 interns), who agreed to answer the Knowledge of Psychiatric Aspects of Alcohol Questionnaire (KPAAQ) anonymously, indicating their gender, year of study and whether they had attended any lecture or workshop on alcohol. KPAAQ consists of 50 questions of 6 clinically relevant categories. Each response to 50 questions of the KPAAQ was assessed. Each correct response was awarded 2 points, thereby, yielding a possible range from 0 to 100 points. Results: The mean knowledge score in medical students was 44.53 (standard deviation = 11.23) without any significant differences (t = 1.171; P > 0.05) between final year students and interns, while the mean knowledge score was significantly more in 74 male students when compared to 106 female students (46.62 ± 10.58; 43.07 ± 11.49) (t = 2.103; P Conclusions: Irrespective of their year of study. Knowledge of psychiatric aspects of AUDs in medical students was inadequate.

Dopaminergic Genetic Variation Influences Aripiprazole Effects on Alcohol Self-Administration and the Neural Response to Alcohol Cues in a Randomized Trial.

Dopamine (DA) signaling regulates many aspects of Alcohol Use Disorder (AUD). However, clinical studies of dopaminergic medications, including the DA partial agonist aripiprazole (APZ), have been inconsistent, suggesting the possibility of a pharmacogenetic interaction. This study examined whether variation in DA-related genes moderated APZ effects on reward-related AUD phenotypes. The interacting effects of APZ and a variable number tandem repeat (VNTR) polymorphism in DAT1/SLC6A3 (the gene encoding the DA transporter (DAT)) were tested. In addition, interactions between APZ and a genetic composite comprising the DAT1 VNTR and functional polymorphisms in catechol-O-methyltransferase (COMT), DRD2, and DRD4 were evaluated. Ninety-four non-treatment-seeking individuals with AUD were genotyped for these polymorphisms, randomized to APZ (titrated to 15 mg) or placebo for 8 days, and underwent an fMRI alcohol cue-reactivity task (day 7; n=81) and a bar lab paradigm (day 8). Primary outcomes were alcohol cue-elicited ventral striatal (VS) activation and the number of drinks consumed in the bar lab. DAT1 genotype significantly moderated medication effects, such that APZ, relative to placebo, reduced VS activation and bar-lab drinking only among carriers of the DAT1 9-repeat allele, previously associated with lower DAT expression and greater reward-related brain activation. The genetic composite further moderated medication effects, such that APZ reduced the primary outcomes more among individuals who carried a larger number of DAT1, COMT, DRD2, and DRD4 alleles associated with higher DA tone. Taken together, these data suggest that APZ may be a promising AUD treatment for individuals with a genetic predisposition to higher synaptic DA tone.

Targeting the subthalamic nucleus in a preclinical model of alcohol use disorder.

The subthalamic nucleus (STN) has only recently been considered to have a role in reward processing. In rats, inactivation of the STN by lesion or high-frequency stimulation (HFS) decreases motivation for cocaine but increases motivation for sucrose. For ethanol, the effect of STN lesion depends on the individual's baseline intake; decreasing motivation for ethanol in rats with lower ethanol intake, while increasing motivation for ethanol in rats with higher-but still limited-ethanol intake. However, the involvement of the STN in behaviour more closely resembling some aspects of alcohol use disorder has not been assessed. This study aimed to determine the effect of STN lesions on the escalation of ethanol intake, subsequent increases in the motivation to "work" for ethanol and the choice of ethanol over a non-drug alternative. We found that STN lesion prevented increases in ethanol intake observed during intermittent ethanol access and after a long period of ethanol privation. STN lesion also decreased the motivation to work for ethanol after escalated intake. Surprisingly, STN lesion increased the choice of alcohol over saccharin. This was associated with a blunting of the hedonic responses to the taste of the reinforcement alternatives. These results evidence the involvement of the STN in different ethanol-motivated behaviours and therefore position the STN as an interesting target for the treatment of alcohol use disorders.

The glucagon-like peptide 1 receptor agonist liraglutide attenuates the reinforcing properties of alcohol in rodents.

The incretin hormone, glucagon‐like peptide 1 (GLP‐1), regulates gastric emptying, glucose‐dependent stimulation of insulin secretion and glucagon release, and GLP‐1 analogs are therefore approved for treatment of type II diabetes. GLP‐1 receptors are expressed in reward‐related areas such as the ventral tegmental area and nucleus accumbens, and GLP‐1 was recently shown to regulate several alcohol‐mediated behaviors as well as amphetamine‐induced, cocaine‐induced and nicotine‐induced reward. The present series of experiments were undertaken to investigate the effect of the GLP‐1 receptor agonist, liraglutide, on several alcohol‐related behaviors in rats that model different aspects of alcohol use disorder in humans. Acute liraglutide treatment suppressed the well‐documented effects of alcohol on the mesolimbic dopamine system, namely alcohol‐induced accumbal dopamine release and conditioned place preference in mice. In addition, acute administration of liraglutide prevented the alcohol deprivation effect and reduced alcohol intake in outbred rats, while repeated treatment of liraglutide decreased alcohol intake in outbred rats as well as reduced operant self‐administration of alcohol in selectively bred Sardinian alcohol‐preferring rats. Collectively, these data suggest that GLP‐1 receptor agonists could be tested for treatment of alcohol dependence in humans.

A Validated Questionnaire to Assess the Knowledge of Psychiatric Aspects of Alcohol Use Disorder

ABSTRACT. Background: To the best of our knowledge, there is no validated instrument for measuring knowledge of psychiatric aspects of alcohol use disorder (AUD) amongst medical students. Our aim was to develop an instrument for this purpose and to describe the instrument's psychometric properties. We also investigated whether the instrument could demonstrate a significant change in scores following an educational intervention consisting of a 60-minute PowerPoint lecture on AUD, associated handouts, and role-plays. Methods: The Knowledge of Psychiatric Aspects of Alcohol Questionnaire (KPAAQ) was developed from the Kaplan and Saddock textbook synopsis chapter on alcohol related disorders. The questionnaire included 6 categories of clinically relevant material: metabolism of alcohol, short-term effects of alcohol, long-term effects of alcohol, AUD, alcohol withdrawal, and alcohol use in pregnancy. The KPAAQ was administered to 75 medical students in Years 4 and 5 from the Hebrew University in Jerusalem, Israel, during a relevant clinical rotation. Following the initial administration of the KPAAQ, the students attended a 60-minute lecture (in Hebrew) based on material from the University of Sydney's learning module on alcohol. The KPAAQ was readministered to the students immediately following the lecture. Results: The KPAAQ demonstrated good reliability (Cronbach α =.92 for all questions) and validity r(209) =.674, P <.001. Knowledge of alcohol and alcoholism significantly increased after the educational intervention (F(2, 154) = 151.60, P <.001). Post hoc comparisons using the Scheffe test revealed a significant positive change in knowledge after students received the intervention (mean difference = 33, P <.001). Conclusions: These initial findings suggest that the KPAAQ is a reliable and valid instrument for assessing medical student knowledge of psychiatric aspects of AUD over 6 clinical categories.

P01-71 - Connections between personality and the symptomatology of alcohol use disorder

IntroductionTemperament and character factors and specific impulse control-related personality traits are connected to the developmental and clinical aspects of alcohol use disorder (AUD).Objectives/aimsTo reveal the underlying personality structure of individual differences in the symptom severity of AUD. Therefore temperament and character, impulsivity and aggression were assessed in relation to alcohol addiction severity.MethodsSixty-three patients with AUD were involved. Temperament and Character Inventory-Revised was used to quantify temperament and character dimensions. Impulsivity was assessed by the Barratt Impulsivity Scale-11 (BIS) and aggression by the Buss-Perry Aggression Questionnaire (BPAQ). To determine symptom severity of AUD the Severity of Alcohol Dependence Questionnaire (SADQ), the Alcohol Use Disorders Identification Test (AUDIT), the MacAndrew Alcoholism Scale-Revised (MAC-R) and the number of DSM-IV alcohol dependence symptoms were registered. To analyze the connections between symptom severity indicators and personality factors Pearson and Spearman correlation analysis were applied, p &lt; 0.05 were considered significant.ResultsSADQ (r = 0.290), AUDIT (r = 0.345), MAC-R (r = 0.504) and the DSM-IV alcohol dependence symptoms (Spearman rho = 0.271) correlated positively with novelty-seeking temperament factor. SADQ (r = 0.262) and AUDIT (r = 0.293) scores correlated positively with BIS. Furthermore SADQ (r = 0.382), AUDIT (r = 0.318), MAC-R (r = 0.416) correlated positively with BPAQ.ConclusionsNovelty-seeking, impulsivity and aggression as indicators of impulse control have different theoretical backgrounds but a common root. This study has revealed that the adverse consequences of lower impulse control can lead to more severe symptoms of AUD. These connections between impulse control and the symptomatology could contribute to a better understanding of the clinical complexity of AUD.

Alcohol Use Disorders in Geriatrics

Alcohol use disorders cause significant morbidity and mortality in the geriatric population. This review article begins with a hypothetical case for illustration, asking what the primary care physician could do for a geriatric patient with alcohol abuse over a course of four office visits. Various aspects of alcohol use disorders in the geriatric population are reviewed, such as range of alcohol use, epidemiology, medical/psychiatric impact, detection, comprehensive treatment planning, modalities of psychotherapy, medication management, and resources for clinicians/patients.