Citalopram Neuropharmacological Challenge in Alcohol-Dependent Patients and Controls: Pharmacogenetic, Endocrine and Psychobehavioral Results
Pharmacopsychiatry 2008; 41: 72-78

Alcoholism has been associated with long-lasting alterations in LHPA (limbic-hypothalamus-pituitary-adrenal) axis function, related to a dysfunction of the serotonergic neurotransmission. Functional polymorphisms of the serotonin system were previously reported to have significant influence on serotonin-induced neuroendocrine response.

The aim of the study is to investigate in a double-blind, placebo-controlled approach, whether citalopram (a selective serotonin reuptake inhibitor, SSRI) would affect LHPA axis function as measured with ACTH (adrenocorticotrophic hormone) levels representing endocrine responsivity in 11 alcohol-dependent individuals compared to 12 controls.

Furthermore we wanted to know whether functional polymorphisms (5-HTTLPR and 5HT2C Ser23Cys), have any influence on this responsivity.

ACTH levels were higher for both groups in the verum compared to placebo administrations across timepoints. 5HT2C Ser23 alleles effected significantly higher ACTH responses under placebo administration but attenuated the responses under citalopram adminsitration. Considering both groups together, no influence of 5-HTTLPR alleles was found on ACTH levels in either group under either regimen. While citalopram adminsitration did not reduce craving in alcohol-dependent patients, it increased anxiety in patients and controls compared to placebo adminstration.

Despite the small differences in endocrine and subjective responses between alcoholic patients and controls, the effect of SSRI on endocrine response with respect to 5HT2C functional alleles deserves further investigation in larger samples to clarify whether this genetic variant constitutes a potential risk factor for changes in neuroendocrine functioning and subsequent psychiatric disorders.

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Request Reprint E-Mail: ulrich.preuss@medizin.uni-halle.de __________________________________________________________

"Culture of Drinking" and Individual Problems with Alcohol Use
American Journal of Epidemiology Advance Access published online on February 29, 2008



Binge drinking is a substantial and growing health problem. Community norms about drinking and drunkenness may influence individual drinking problems.

Using data from the New York Social Environment Study (n = 4,000) conducted in 2005, the authors examined the relation between aspects of the neighborhood drinking culture and individual alcohol use. They applied methods to address social stratification and social selection, both of which are challenges to interpreting neighborhood research.

In adjusted models, permissive neighborhood drinking norms were associated with moderate drinking (odds ratio (OR) = 1.28, 95% confidence interval (CI): 1.05, 1.55) but not binge drinking; however, social network and individual drinking norms accounted for this association.

By contrast, permissive neighborhood drunkenness norms were associated with more moderate drinking (OR = 1.20, 95% CI: 1.03, 1.39) and binge drinking (OR = 1.92, 95% CI: 1.44, 2.56); the binge drinking association remained after adjustment for social network and individual drunkenness norms (OR = 1.58, 95% CI: 1.20, 2.08).

Drunkenness norms were more strongly associated with binge drinking for women than for men (p_interaction = 0.006).

Propensity distributions and adjustment for drinking history suggested that social stratification and social selection, respectively, were not plausible explanations for the observed results.

Analyses that consider social and structural factors that shape harmful drinking may inform efforts targeting the problematic aspects of alcohol consumption.

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Genetic association of DRD2 polymorphisms with anxiety scores among alcohol-dependent patients
Biochemical and Biophysical Research Communications Article in Press, Uncorrected Proof 25 February 2008


The dopaminergic neurotransmission system is one of the major factors in development of alcoholism and also contributes to anxiety and depression.

In this study, the associations of the dopamine receptor type 2 (DRD2) polymorphisms with the symptoms of anxiety were analyzed.

A total of 573 alcoholics and 273 controls were enrolled in the study from the Korean population. Five DRD2 SNPs, including −32869 A>G, −32768 insdel C, +11890 C>G, +11915 C>T, and +32806 C>T, were genotyped using a TaqMan assay and analyzed with various alcoholic phenotypes.

Although no DRD2 polymorphisms were associated with the risk of alcoholism, +32806 C>T and Block2-ht1 showed associations (in dominant models) with both the state anxiety level scale (STAI-S) and the trait anxiety level scale (STAI-T) (P = 0.004 and P = 0.003, and P = 0.01 and P = 0.005, respectively).

In addition, the −32768 insdel C also showed positive association with both anxiety level scales in recessive models (P = 0.01 and P = 0.02, respectively).

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Alcohol preference in mice lacking the Avpr1a vasopressin receptor
Am J Physiol Regul Integr Comp Physiol (February 27, 2008)

Arg⁸]-Vasopressin (Avp), a nonapeptide hormone, is known to regulate blood pressure, water balance, and a variety of behaviors such as anxiety, aggression, and bonding. Although some evidence that Avp modifies ethanol consumption and some of the effects of ethanol on behavior have been reported, the role of Avp in alcohol consumption and preference is poorly understood. The Avp 1a receptor (Avpr1a) is ubiquitously expressed in the central nervous system.

To determine the role of Avp signaling on the behavioral effects of alcohol, we examined voluntary ethanol consumption in mice with targeted disruptions of the Avpr1a (Avpr1a KO) gene. Avpr1a KO mice displayed both increased ethanol consumption and preference compared with the wild-type (WT) mice.

The enhanced ethanol consumption was dramatically and reversibly reduced by treatment with NMDA antagonists. Basal glutamate release was elevated around the striatum in Avpr1a KO mice. The elevation of extracellular glutamate was also produced in WT mice by local application of an Avpr1a antagonist though a dialysis probe, and this elevation was quickly reversed by stopping the perfusion.

These results suggest that Avp can inhibit the release of glutamate from the presynaptic terminal via the Avp 1a receptor and that elevation of glutamate levels owing to loss of the inhibitory effect via Avp-Avpr1a signaling may play an important role in the preference for ethanol.

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Ethnic Differences in Level of Response to Alcohol Between Chinese Americans and Korean Americans
J. Stud. Alcohol Drugs 69: 227-234,




Koreans have higher rates of alcohol-use disorders and family history of alcoholism, compared with Chinese. These differences likely reflect both environmental and genetic influences.

One genetically influenced characteristic that may contribute to these ethnic differences is level of response to alcohol. Variant alleles of aldehyde dehydrogenase (ALDH2) and alcohol dehydrogenase (ADH1B) genes are prevalent in individuals of Asian heritage and have been associated with an increased level of response to alcohol and a decreased risk for alcohol dependence.

Additionally, a low level of response to alcohol is more common in individuals with a first-degree family history of alcoholism and is predictive of increased risk for this disorder. It also is possible that sociocultural factors have an impact on an individual's response to alcohol.

The current study examined self-report level of response to alcohol, ALDH2 and ADH1B, country of origin, and family history of alcoholism in 154 Chinese- and 181 Korean-American college students.

Ethnicity was significantly related to level of response to alcohol, with Koreans having a lower self-reported level of response than Chinese. This relationship remained significant after considering the effects of gender, height, weight, quantity and frequency of alcohol consumption (over the previous 90 days), ALDH2 genotype, ADH1B genotype, country of origin, and first-degree family history of alcohol dependence.

The results suggest that a low level of response to alcohol may contribute to the increased risk for alcohol abuse and dependence found in Koreans, relative to Chinese.

More research is needed to determine additional factors that may be contributing to the low alcohol response and high rates of alcoholism in Koreans.

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Request Reprint E-Mail: mschuckit@ucsd.edu
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Public Alcohol Policy: Current Directions and New Opportunities
Clinical Pharmacology & Therapeutics (2008) Advance Online 27 February 2008


Alcohol policy has been shown to have an impact on the incidence and prevalence of alcohol "addiction," or alcohol use disorders (AUDs), as currently defined by the International Classification of Diseases, volume 10, or by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition.

We will mainly use the term "addiction" to depict a state involving loss of control over intense urges to consume alcohol, even at the expense of adverse consequences. This definition goes beyond pure "physiological dependence."¹

We will use the term AUD when referring to statistics based on the above-described definitions.

In this overview we identify the pathways in the relationship between alcohol policy and addiction, present the empirical evidence, and draw conclusions. Special emphasis will be put on treatment policy.

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Chronic Alcohol Feeding Induces Biochemical, Histological, and Functional Alterations in Rat Retina Alcohol and Alcoholism Advance Access published online on February 27, 2008


Ethanol consumption originates a wide spectrum of disorders, including alteration of visual function. Oxidative stress is included among the mechanisms by which alcohol predisposes nervous tissue to injury. Retina, which is the neurosensorial eye tissue, is particularly sensitive to oxidative stress.

In this study we analyze the effect of long-term alcohol consumption on oxidative stress parameters of the rat retina, and its correlation to retinal function, as well as to the expression of the antiapoptotic protein Bcl-2. We also study the protective effect of ebselen, a synthetic selenoorganic antioxidant.

Herein we show that ethanol has a toxic effect on rat retina associated with oxidative stress. Decreases in retina glutathione concentration and increases in malondialdehyde content in whole eye homogenate significantly correlate with ERG b-wave decrease and Bcl-2 overexpression. We also show how ebselen is able to prevent all the alterations observed.

Chronic ethanol consumption induces oxidative stress in rat retina associated with an impairment of ERG and Bcl-2 overexpression, suggesting a role for glial cells. All these alterations in the rat allow the proposal of an alcoholic retinopathy in this species.


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Alcohol-related adverse consequences: cross-cultural variations in attribution process among young adults
The European Journal of Public Health Advance Access published online on February 19, 2008


Social norms around what is culturally accepted in terms of alcohol consumption and drunken comportment appear important regarding the acceptance of alcohol-related adverse consequences; however, investigations often neglect to consider differences in terms of attribution.

This study aims at assessing cross-cultural differences in the reporting of alcohol-related adverse consequences. It also considers differences across consequences that might explain which type of consequences (mainly acute or mainly chronic) are most affected by an attribution process.

Differences among the patterns of associations between countries and consequences were evident. The distinction between Nordic and other European countries was persistent. A higher variability of associations was observed for some consequences, namely the mainly acute instances. Finally, the Isle of Man and Switzerland showed specific trends with associations across consequences.

Reporting of alcohol-related adverse consequences seemed strongly affected by cultural norms. The latter may be exemplified by viewing drinking as ‘time-out’ behaviour. Respondents in countries with a stereotypical history of being ‘dry’ or with a stereotyped ‘binge’ drinking culture were more likely to attribute consequences to their alcohol consumption than people in ‘wet’ countries. This was particularly true for consequences that related to episodic ‘time-out’ heavy drinking.


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Age at Drinking Onset, Alcohol Dependence, and Their Relation to Drug Use and Dependence, Driving Under the Influence of Drugs, and Motor-Vehicle Crash Involvement Because of Drugs
J. Stud. Alcohol Drugs 69: 192-201, 2008


We explored among people who ever consumed alcohol whether early age at drinking onset and alcohol dependence predicted drug use and dependence. We also examined among drinkers who have used drugs whether they also predict driving under the influence of drugs and motor-vehicle crash involvement because of drugs.

Among ever drinkers, 22% used drugs, 10% had driven under the influence of drugs, and nearly 1% was in a motor-vehicle crash because of drug use, the equivalent of 1 million people. The younger the age of respondents when they first began drinking and whether they ever experienced alcohol dependence were independently associated with greater odds of ever using drugs and experiencing drug dependence.

Among persons who consumed alcohol and drugs, having ever experienced drug dependence was the strongest predictor of driving under the influence of drugs and motor-vehicle crash involvement because of drug use. After controlling for drug dependence and age at first drug use, having experienced alcohol dependence was also independently associated with both outcomes.

Efforts to prevent drug-related crashes should include drug use prevention and treatment, as well as prevention of early alcohol use and treatment of alcohol dependence.


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What Addicts Need

Addiction isn't a weakness; it's an illness. Now vaccines and other new drugs may change the way we treat it.

By Jeneen Interlandi | NEWSWEEK 12:43 PM ET February 23, 2008

Annie Fuller knew she was in trouble a year ago, when in the space of a few hours she managed to drink a male co-worker more than twice her size under the table. Of course, she'd been practicing for a quarter of her life by then; at 47, she was pouring a pint of bourbon, a 12-pack of beer and a couple of bottles of wine into her 115-pound body each day. She had come to prefer alcohol to food, sex or the company of friends and loved ones. Her marriage had ended; she had virtually stopped leaving the house, except to work and to drink. Fuller had tried and failed enough times over the years to know that she would not be able to sober up on her own.

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Alcohol Information Pack for Offenders under Probation Supervision

An alcohol information pack for offenders under Probation supervision has been developed by the Interventions and Substance Abuse Unit in conjunction with Alcohol Concern and MP Consultancy. The purpose of the pack is to provide offender managers with clear guidance and tools to:

• Identify offenders with alcohol related needs.
• Deliver ‘brief interventions’ to offenders with lower level alcohol problems
• Offer support and onward referral to those who may need more intensive intervention.

The pack includes sections on the probation service’s role in addressing offenders’ alcohol misuse needs; general alcohol information; specific offender groups and issues; and routes into treatment. There are also a number of exercises for offenders to work through either on their own or with their offender manager and a validated alcohol screening tool (AUDIT).

As is made clear in the accompanying guide for offender managers, the pack is not intended for use as a single document. Therefore, the five main sections are attached separately to make it easier for offender managers to extract and use whatever material is most appropriate in each specific case.

Date: Tue Feb 26 2008

• Alcohol Information Pack (382 K )
• Alcohol Information Pack - Guide for Offender Managers (88 K )
• Alcohol Information Pack, Section 1 - Probation Service's Role (47 K )
• Alcohol Information Pack, Section 2 - General Alcohol Information (196 K )
• Alcohol Information Pack, Section 3 - Specific Offender Groups and Issues (79 K )
• Alcohol Information Pack, Section 4 - Motivational Interventions (138 K )
• Alcohol Information Pack, Section 5 - Routes into Treatment (62 K )

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Alcohol-related deaths – latest UK figures for 2006
Health Statistics Quarterly 37 Spring 2008 p. 3




Latest figures on alcohol-related death rates in the UK in 2006 were released on 25 January 2008. Rates in the UK continued to increase, rising from 12.9 deaths per 100,000 population in 2005 to 13.4 in 2006. Rates almost doubled from 6.9 per 100,000 in 1991. The number of alcohol-related deaths more than doubled from 4,144 in 1991 to 8,758 in 2006.

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Adolescent problem behaviours predicting DSM-IV diagnoses of multiple substance use disorder
Social Psychiatry and Psychiatric Epidemiology, Online Early 27 Febrauary 2008

Whether there is an independent association between problem behaviours and substance use disorders (SUD) needs further investigation.

This study examined prospective associations of adolescent psychopathology and problem behaviours with SUD in early adulthood, and whether these associations are confounded by other factors.

In multivariate analyses, attention problems, delinquency, and aggression were associated with both single and multiple SUD in early adulthood, with delinquent behaviour being the strongest predictor (OR = 2.0, 95% CI 1.4–2.9 for one SUD and OR = 3.6, 95% CI 2.4–5.0 for multiple SUDs).

Problem behaviours, in particular delinquency and aggression in early adolescence predict long-term SUD. The results suggest that substance use prevention programs should target adolescents with early symptoms of psychopathology and problem behaviour.

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Request Reprint E-Mail: m.hayatbakhsh@sph.uq.edu.au
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Effectiveness of brief alcohol interventions for general practice patients with problematic drinking behavior and comorbid anxiety or depressive disorders
Drug and Alcohol Dependence Volume 94, Issues 1-3, 1 April 2008, Pages 214-220

Brief interventions (BIs) are effective methods to reduce problematic drinking. It is not known, if the effectiveness of BI differs between patients with or without comorbid depression or anxiety disorders.

BI were significantly related to reduction of drinking in the non-comorbid (−2.64 g/alcohol vs. −8.61 g/alcohol; p = .03) but not in the comorbid subsample (−22.06 g/alcohol vs. −22.09 g/alcohol; p = .76). Compared to non-comorbid participants, a significantly higher reduction of drinking was found for comorbid individuals (−6.55 g/alcohol vs. −22.08 g/alcohol; p = .01). An ordinal regression analysis revealed comorbidity to be a positive predictor for reduction of drinking (estimator = .594; CI = .175–1.013; p < .01). When entering the variables amount of drinking at baseline, intervention and classification of problematic drinking, these became significant predictors, whereas comorbidity showed only a tendency.

BI did not significantly effect a reduction of drinking in comorbid patients. As BI are known to be less effective for dependent drinkers, a larger proportion of dependents among the comorbid might have limited the effectiveness of BI.

Future studies with larger sample sizes of comorbid problem drinkers are necessary to confirm the results.

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Request Reprint E-Mail: Janina.Grothues@psychiatrie.uk-sh.de

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Reliability of a rating procedure to monitor industry self-regulation codes governing alcohol advertising content.
Stud. Alcohol Drugs 69:J. 235-242, 2008


The purposes of this study were to develop reliable procedures to monitor the content of alcohol advertisements broadcast on television and in other media, and to detect violations of the content guidelines of the alcohol industry's self-regulation codes.

A set of rating-scale items was developed to measure the content guidelines of the 1997 version of the U.S. Beer Institute Code. Six focus groups were conducted with 60 college students to evaluate the face validity of the items and the feasibility of the procedure. A test-retest reliability study was then conducted with 74 participants, who rated five alcohol advertisements on two occasions separated by 1 week.

Average correlations across all advertisements using three reliability statistics (r, rho, and kappa) were almost all statistically significant and the kappas were good for most items, which indicated high test-retest agreement. We also found high interrater reliabilities (intraclass correlations) among raters for item-level and guideline-level violations, indicating that regardless of the specific item, raters were consistent in their general evaluations of the advertisements.

Naïve (untrained) raters can provide consistent (reliable) ratings of the main content guidelines proposed in the U.S. Beer Institute Code. The rating procedure may have future applications for monitoring compliance with industry self-regulation codes and for conducting research on the ways in which alcohol advertisements are perceived by young adults and other vulnerable populations.

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Request Reprint E-Mail: babor@nso.uchc.edu
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Kinetics and Isoforms of Serum Glutamate Dehydrogenase in Alcoholics
Alcohol and Alcoholism Advance Access published online on February 27, 2008


The goal of this paper was to determine Glutamate dehydrogenase's (GLDH) increased activity and rapid decrease in alcoholics according to last consumption of alcohol as well as to confirm that quick normalisation cannot be a sign of hepatocyte necrosis and that GLDH from rough endoplasmic reticulum exists in the serum of alcoholics.

Alcoholics were ascertained to have statistically significantly higher mean GLDH serum activities (men 351.53 nkat/L, women 296.08 nkat/L); the higher the level, the less elapsed time there was after the latest alcohol intake. There was an increased GLDH activity in 65.5% of alcoholics; furthermore, the percentage rose sharply to 72.2% with those who had last consumed alcohol within 48 hours. In the serum of alcoholics, it was found that, on average, it was 32.4% thermo-stable and 67.6% thermo-labile GLDH, which means that almost one third of GLDH serum originates from rough endoplasmic reticulum and rest from mitochondria. This is a completely new finding.

A statistically significant fast decrease of GLDH serum activity after a break in alcohol consumption has been confirmed. It is estimated that increased GLDH activity in the sera of alcohol dependents and its fast decrease after total abstinence has been restored are specific for alcohol addiction.

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Distinct patterns of FosB induction in brain by drugs of abuse

Synapse 358-369, 2008.


The transcription factor FosB accumulates and persists in brain in response to chronic stimulation. This accumulation after chronic exposure to drugs of abuse has been demonstrated previously by Western blot most dramatically in striatal regions, including dorsal striatum (caudate/putamen) and nucleus accumbens.

In the present study, we used immunohistochemistry to define with greater anatomical precision the induction of FosB throughout the rodent brain after chronic drug treatment. We also extended previous research involving cocaine, morphine, and nicotine to two additional drugs of abuse, ethanol and ⁹-tetrahydrocannabinol (⁹-THC, the active ingredient in marijuana).

We show here that chronic, but not acute, administration of each of four drugs of abuse, cocaine, morphine, ethanol, and ⁹-THC, robustly induces FosB in nucleus accumbens, although different patterns in the core vs. shell subregions of this nucleus were apparent for the different drugs.

The drugs also differed in their degree of FosB induction in dorsal striatum. In addition, all four drugs induced FosB in prefrontal cortex, with the greatest effects observed with cocaine and ethanol, and all of the drugs induced FosB to a small extent in amygdala.

Furthermore, all drugs induced FosB in the hippocampus, and, with the exception of ethanol, most of this induction was seen in the dentate. Lower levels of FosB induction were seen in other brain areas in response to a particular drug treatment.

These findings provide further evidence that induction of FosB in nucleus accumbens is a common action of virtually all drugs of abuse and that, beyond nucleus accumbens, each drug induces FosB in a region-specific manner in brain.

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Request Reprint E-Mail: eric.nestler@utsouthwestern.edu
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Memory patterns of acquisition and retention of verbal and nonverbal information in children with fetal alcohol spectrum disorders
Can J Clin Pharmacol Vol 15(1) Winter 2008:e44-e56; January 9, 2008

Previous research indicates that children with FASD have both memory and learning deficits. However, there is no consensus about whether the deficits identified from a pattern of impairment, and whether this pattern is consistent with the current theories regarding the organization of memory. Thus, the goal of this study was to further explore memory functions and expose possible patterns that may exist in children with FASD.

A significant difference between types of verbal memory in the FASD sample was identified. Specifically, recall of word pairs was found to be more impaired than that for stories. In addition to this, recall of immediate word pairs was significantly more impaired than that for delayed word pairs, implying the presence of encoding deficits in this area.

Children and adolescents with FASD displayed specific types of verbal memory deficits and these deficits were greater for immediate rather than delayed memory. These data are consistent with previous studies that describe deficits in immediate memory, and suggest that deficits in delayed memory are better accounted for by encoding deficits. Furthermore, their greatest difficulty arose with those items in which the phonological loop was required, which would have facilitated learning though internal recitation and adequate phonological storage.

Further research into these distinctions in memory is warranted, as is exploration into educational techniques that could account for delayed encoding in children with FASD.

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Fetal alcohol syndrome related knowledge assessment and comparison in New Jersey health professional groups
Can J Clin Pharmacol Vol 15(1) Winter 2008:e57-e65; January 9, 2008

There is a need to educate health professionals in regard to Fetal Alcohol Syndrome and Fetal Alcohol Spectrum Disorders across many health and allied health fields.

Conduct evaluations of educational programs designed to assess knowledge, attitudes and beliefs in relation to Fetal Alcohol Spectrum Disorders (FASD) among health and allied health professionals in the northeastern United States.


Results showed that a majority of health care professionals in New Jersey possess basic knowledge related to FASD and the effects of alcohol on a child in utero. They also had significant awareness of the importance of early diagnosis and the importance of reducing secondary disabilities. The study did however reveal areas for improvement in some professional groups.

FASD is the most important preventable cause of mental retardation. Health professionals attending workshops typically had a good basic understanding of FASD, though with some weaknesses specific to their discipline. Educational efforts in regard to FASD should be sensitive to the various health professionals engaged in preventing, diagnosing and treating FASD.

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Perspectives of mothers with substance use problems on father involvement
Can J Clin Pharmacol Vol 15(1) Winter 2008:e99-e107; February 1, 2008

A number of complex factors contribute to pregnant and parenting women’s alcohol and substance use. To date, little research has focused on the implications, meaning and experiences of father involvement on mothers with substance use problems.

The current study explores the experiences of mothers with substance use problems with respect to the role, impact and meaning of father involvement.

The meaning of father involvement among this group of women centered on four dimensions: emotional support, financial contributions to the family, amount and quality of time spent with the children and the family, and was dependent upon the particular expectations of the mother involved. Barriers and influences of father involvement were identified. The nature of father involvement had negative and positive impacts on participants.

Maternal use of alcohol is a complex issue, one factor often ignored in father involvement. For mothers with substance use problems father involvement has a number of implications, both positive and negative.

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