White blood cells and patients with psychiatric disorders needing seclusion: A retrospective non-interventional study.

OBJECTIVE: The objective of this retrospective study was to investigate the peripheral immunological markers using leucocyte count, the neutrophil to lymphocyte ratio (NLR), the platelet to lymphocyte ratio (PLR), and the monocyte to lymphocyte ratio (MLR) in patients with aggressive behavior, during and after seclusion. METHODS: Ninety-nine inpatients were included in this retrospective study. Leucocyte count was measured, and NLR, PLR and MLR were calculated and compared between a group of patients who required seclusion and a group who did not. A multivariate analysis was performed using binary logistic regression, including confounding factors such as age, gender, medication, BMI, smoking status and diagnosis. RESULTS: We found the lowest levels of lymphocytes (P=0.01) and basophils (P<0.01) and the highest NLR (P=0.02) and MLR (P=0.04) in the seclusion group. We also found a restoration of these parameters after the end of the seclusion period. Furthermore, we found a positive correlation between the PANSS negative subscore, and PLR (P=0.05), or MLR (P=0.03) after seclusion, and between the MLR variation across the seclusion period and the PANSS general subscore after the end of seclusion (P=0.04). CONCLUSION: This study shows that NLR and MPR are higher in patients with aggressive symptoms and/or agitation who require seclusion. These immunological markers could be considered as state markers.

Cannabidiol in the context of substance use disorder treatment: A systematic review.

INTRODUCTION: Cannabidiol (CBD) is a phytocannabinoid found in the Cannabis plant. CBD has received significant medical attention in relation to its anticonvulsant, anxiolytic, and antipsychotic characteristics. An increasing number of studies focusing on the anti-addictive properties of CBD have recently been published. In this systematic review, we aim to offer a comprehensive overview of animal and human studies regarding the impact of CBD on substance use disorders (SUDs). METHODS: A systematic search was performed on the PubMed database in February 2021. We included all articles assessing the effects of CBD on substance use disorders. RESULTS: The current systematic review suggests that CBD might offer promising therapeutic potential for the treatment of SUD, based on available animal and human studies. Animal studies showed a positive impact of CBD in the context of alcohol, opioids, and methamphetamine use (e.g., diminishing of drug-seeking behaviors). The results for cocaine use were mixed among reviewed studies, and CBD was not found to have an effect in animal studies on cannabis use. No animal study was identified that focused on the impact of CBD on nicotine use. Human studies showed a positive impact of CBD in the context of nicotine, cannabis, and opioid use (e.g., frequency and quantity of consumption). In contrast, CBD was not found to have an effect in human studies on cocaine or alcohol use. No human study was identified that investigated the impact of CBD on methamphetamine use. CONCLUSIONS: CBD might offer promising therapeutic potential for the treatment of SUD, especially for nicotine, cannabis, and opioid use disorders, based on available human studies. The available research evidence is, however, sparse and more research on humans is needed.

Psychological Distress and Tobacco Use Among Hospital Workers During COVID-19.

Background and Aims: This work aims to assess the impact of the COVID-19 pandemic on hospital workers' psychological parameters and attitudes toward substance use, before and during the French COVID-19 lockdown. Methods: An online survey was proposed to the staff of the University Hospital of Nice and Sainte-Marie psychiatric hospital in France from May 18 to June 6, 2020 assessing changes in daily habits, psychological distress and changes in substance use, including smoking. Results: A total of 702 respondents (80.3% female) filled out the survey. Overall, most of the workers reported increased stress, irritability, sadness, decreased motivation, and a worse quality of sleep after the beginning of the COVID-19 lockdown. Additionally, hospital workers who were more likely to use tobacco during the COVID-19 lockdown reported increased sadness (OR = 1.23, p < 0.001), loss of motivation (OR = 0.86, p < 0.05), alcohol consumption (OR = 3.12, p < 0.001), lower incomes (OR = 1.69, p < 0.05), living alone (OR = 1.77, p < 0.001) and doing less physical activity (OR = 0.36, p < 0.001). Conclusion: During the first lockdown, significant psychological changes (sadness, distress, irritability) associated with changes in tobacco use and physical activity were reported. Such results should encourage hospital leaders to implement dedicated policies to better accompany hospital workers' psychological distress.

Clinical and biological predictors of psychedelic response in the treatment of psychiatric and addictive disorders: A systematic review.

BACKGROUND: The use of psychedelic treatments has shown very promising results in some psychiatric and addictive disorders, but not all patients achieved a response. AIM: The aim of this review is to explore the clinical and biological factors which could predict the response to psychedelics in psychiatric and addictive disorders. METHODS: A systematic research was performed on MEDLINE, PsycInfo, Web of science, and Scopus databases from January 1990 to May 2020. All studies investigating the predictive factors of response to psychedelics regardless of psychiatric or addictive disorders, were included. RESULTS: Twenty studies investigating addictive disorder, treatment-resistant depression, obsessive-compulsive disorder and depressive and anxiety symptoms in patients with life-threatening cancer were included in this review. We found that, in all indications, the main predictive factor of response to psychedelics is the intensity of the acute psychedelic experience. Indeed, we found this factor for alcohol and tobacco use disorders, treatment-resistant depression, and anxiety and depressive symptoms in patients with life-threatening cancer, but not for obsessive-compulsive disorder. CONCLUSION: The intensity of the acute psychedelic experience was the main predicting factor of response. The action mechanism of this experience was not clear, but some hypotheses could be made, such as a modulation of serotoninergic system by 5-HT2A receptors agonism, a modulation of the default mode network (DMN) with an acute modular disintegration of the DMN followed by a re-integration of this network with a normal functioning, or an anti-inflammatory effect of this treatment.

Global Changes and Factors of Increase in Caloric/Salty Food Intake, Screen Use, and Substance Use During the Early COVID-19 Containment Phase in the General Population in France: Survey Study.

BACKGROUND: The international outbreak of coronavirus disease (COVID-19) has led many countries to enforce drastic containment measures. It has been suggested that this abrupt lockdown of populations will foster addiction-related habits such as caloric/salty food intake, screen use, and substance use. OBJECTIVE: Our aim was to assess the global changes and factors of increase in addiction-related habits during the early COVID-19 containment phase in France. METHODS: A web-based survey was provided from day 8 to day 13 of the containment and was completed by 11,391 participants. The questions explored sociodemographic features, psychiatric/addiction history, material conditions of lockdown, general stress, mental well-being, and reported changes in several addiction-related behaviors. Global changes were described and factors of increase were explored using population-weighted and adjusted logistic regression models, providing adjusted odds ratios (aORs) and their 95% confidence intervals. RESULTS: Overall, the respondents reported more increases in addiction-related habits than decreases, specifically 28.4% (caloric/salty food intake), 64.6% (screen use), 35.6% (tobacco use), 24.8% (alcohol use), and 31.2% (cannabis use). Reduced well-being scores and increased stress scores were general factors of increase in addiction-related habits (P<.001 for all habits). Factors of increase in caloric/salty food intake (n=10,771) were female gender (aOR 1.62, 95% CI 1.48-1.77), age less than 29 years (P<.001), having a partner (aOR 1.19, 95% CI 1.06-1.35), being locked down in a more confined space (per 1 square meter/person decrease: aOR 1.02, 95% CI 1.01-1.03), being locked down alone (aOR 1.29, 95% CI 1.11-1.49), and reporting current (aOR 1.94, 95% CI 1.62-2.31) or past (aOR 1.27, 95% CI 1.09-1.47) psychiatric treatment. Factors of increase in screen use (n=11,267) were female gender (aOR 1.31, 95% CI 1.21-1.43), age less than 29 years (P<.001), having no partner (aOR 1.18, 95% CI 1.06-1.32), being employed (P<.001), intermediate/high education level (P<.001), being locked down with no access to an outdoor space (aOR 1.16, 95% CI 1.05-1.29), being locked down alone (aOR 1.15, 95% CI 1.01-1.32), living in an urban environment (P<.01), and not working (P<.001). Factors of increase in tobacco use (n=2787) were female gender (aOR 1.31, 95% CI 1.11-1.55), having no partner (aOR 1.30, 95% CI 1.06-1.59), intermediate/low education level (P<.01), and still working in the workplace (aOR 1.47, 95% CI 1.17-1.86). Factors of increase in alcohol use (n=7108) were age 30-49 years (P<.05), a high level of education (P<.001), and current psychiatric treatment (aOR 1.44, 95% CI 1.10-1.88). The only significant factor of increase in cannabis use (n=620) was intermediate/low level of education (P<.001). CONCLUSIONS: The early phase of COVID-19 containment in France led to widespread increases in addiction-related habits in the general population. Reduced well-being and increased stress were universal factors of increase. More specific factors were associated with increases in each of the explored habits.

Chronic smoking and cognition in patients with schizophrenia: A meta-analysis.

BACKGROUND: Patients with schizophrenia display a very high rate of smoking in comparison with the general population. The aim of the present meta-analysis was to assess the association between cognitive performances and smoking status in patients with schizophrenia. METHODS: This review was registered at PROSPERO, number CRD42019126758. After a systematic search on MEDLINE, PsycINFO, and clinicaltrials.gov databases, all studies measuring neurocognitive performances in both smoking and nonsmoking patients with a diagnosis of schizophrenia were included. Original data were extracted. Standardized mean differences (SMD) were calculated with the means and standard deviations extracted using a random-effect model. Cognitive performances were compared between smoking and nonsmoking patients with schizophrenia. Meta-regressions were performed to explore the influence of sociodemographic and clinical variables on SMD. RESULTS: Eighteen studies were included in this meta-analysis. Chronic smoking in patients with schizophrenia, compared to nonsmoking, was associated with a significant more important impairment in attention (p = 0.02), working memory (p < 0.001), learning (p < 0.001), executive function (EF) reasoning/problem solving (p < 0.001) and speed of processing (p < 0.001), but not in delayed memory, EF abstraction/shifting, EF inhibition and language. The meta-regression analysis found that attention impairment could be influenced by age (p < 0.001) and Positive and Negative Syndrome Scale (PANSS) total score (p = 0.006). CONCLUSIONS: This meta-analysis provides strong evidence that, in patients with schizophrenia, chronic smoking is related to cognitive impairment. This association emphasizes the importance of paying careful attention to both tobacco addiction and cognitive functioning in patients with schizophrenia.

Several clock genes polymorphisms are meaningful risk factors in the development and severity of cannabis addiction.

Circadian rhythms have been related to psychiatric diseases and regulation of dopaminergic transmission, especially in substance abusers. The relationship between them remained enigmatic and no data on the role of clock genes on cannabis dependence have been documented. We aimed at exploring the role of clock gene genotypes as potential predisposing factor to cannabis addiction, using a high throughput mass spectrometry methodology that enables the large-scale analysis of the known relevant polymorphisms of the clock genes. We have conducted a case-control study on 177 Caucasians categorizing between cannabis-addicted subjects and casual consumers based on structured interviews recorded socio-demographic data, AUDIT, Fagerström test, MINI, and medical examinations. Alcohol, opiates, and stimulants' consumption was as exclusion criteria. We report an association between several Single Nucleotide Polymorphism (SNP)s in main circadian genes SNPs, especially the gene locus HES7/PER1 on chromosome 17 and cannabis consumption as well as the development of neuropsychiatric and social disorders. This SNP's signature that may represent a meaningful risk factor in the development of cannabis dependence and its severity requires to be deeply explored in a prospective study.

Kinetics of Cytokine Levels during Antipsychotic Treatment in Schizophrenia: A Meta-Analysis.

Background: Immune system dysfunction is a hypothesis in the psychopathology of schizophrenia, but the impact of antipsychotic treatment within this system is not clear. The aim of this meta-analysis was to investigate the impact of antipsychotic treatment on cytokine levels in in vivo studies on schizophrenia. Methods: After a systematic database search, original data were extracted with the help of certain authors. Means and SDs were extracted to calculate standardized mean differences. Cytokine levels were compared in vivo in schizophrenia patients, before and after antipsychotic treatment. Meta-regressions were performed to explore the influence of demographic and clinical variables on cytokine level standardized mean differences. Stratifications by treatment and diagnosis were also performed. Results: Forty-seven studies were included in this meta-analysis. Proinflammatory cytokine level decreases were found for interleukin-1 ß levels (P<.0001) and interferon-γ (P=.01) and a statistical trend towards a decrease in interleukin-6 (P=.08) and tumor necrosis factor-α (P=.07) levels. An antiinflammatory cytokine level increase was found for soluble tumor necrosis factor-R2 (P<.001) and soluble interleukin 2-R (P=.03) levels. A meta-regression analysis found a correlation between interleukin-6 level standardized mean differences and positive schizophrenia symptom score standardized mean differences before and after treatment (P=.01). Stratification by diagnosis or treatment found a possible impact of the kinetics of cytokine levels. Conclusions: The present meta-analysis provides evidence that antipsychotic treatment has an antiinflammatory effect and could normalize immune balance dysfunction in schizophrenia. Interleukin-6 level normalization could be a marker of illness equilibration and thus used in clinical practice.

Tobacco use is associated with increased plasma BDNF levels in depressed patients.

Since serum Brain Derived Neurotrophic Factor (BDNF) levels are higher in tobacco smokers than in non-smokers and since Major Depressive Disorder (MDD) is associated with a 2-fold increased risk of smoking, we assessed the association of smoking and plasma BDNF levels in 359 depressed MDD patients. Plasma BDNF levels were positively correlated with the magnitude of tobacco consumption (current number of cigarettes/day and number of packs/year). Accordingly, current tobacco users had significantly higher plasma BDNF levels than non-users. In further studies of MDD, peripheral measures of BDNF should take into account tobacco use.

The Synthetic Cannabinoids Phenomenon.

« Spice ¼ is generally used to describe the diverse types of herbal blends that encompass synthetic cannabinoids on the market. The emergence of smokable herbal products containing synthetic cannabinoids, which mimic the effects of cannabis, appears to become increasingly popular, in the new psychoactive substances landscape. In 2014, the existence of 134 different types of synthetic cannabinoids were reported by the European Union Early Warning System. These drugs are mainly sold online as an alternative to controlled and regulated psychoactive substances. They appear to have a life cycle of about 1-2 years before being replaced by a next wave of products. Legislation controlling these designer drugs has been introduced in many countries with the objective to limit the spread of existing drugs and control potential new analogs. The majority of the synthetic cannabinoids are full agonists at the CB1 receptor and do not contain tobacco or cannabis. They are becoming increasingly popular in adolescents, students and clubbers as an abused substance. Relatively high incidence of adverse effects associated with synthetic cannabinoids use has been documented in the literature. Numerous fatalities linked with their use and abuse have been reported. In this paper, we will review the available data regarding the use and effects of synthetic cannabinoids in humans in order to highlight their impact on public health. To reach this objective, a literature search was performed on two representative databases (Pubmed, Google Scholar), the Erowid Center website (a US non-profit educational organization that provides information about psychoactive plants and chemicals), and various governmental websites. The terms used for the database search were: "synthetic cannabinoids", "spice", "new psychoactive substances", and/or "substance use disorder", and/or "adverse effects", and/or "fatalities". The search was limited to years 2005 to 2016 due to emerging scientific literature at this period Health professionals should take into account that limited scientific evidence is available regarding the effect of synthetic cannabinoids use in humans. It thus urges to launch more systematic epidemiological studies, to develop and validate screening procedures, and to investigate the neurobiological and psychological correlates and risk factors associated to synthetic cannabinoids use and misuse.

The effects and risks associated to mephedrone and methylone in humans: A review of the preliminary evidences.

New psychoactive substances have drastically modified the world drug scene. An increasingly popular class comprises synthetic or substituted cathinones (legal highs, research chemicals, bath salts). Among the most common psychoactive constituents of bath salts are mephedrone and methylone. Recent reports on the abuse of novel synthetic cathinone derivatives call attention to the serious physical and psychological risks resulting from their consumption, thereby emphasizing the growing use of these drugs might constitute an important public health issue. In this paper, we will review the available data regarding the use and effects of mephedrone and methylone in humans in order to highlight their impact on public health. To reach this objective, a literature search was performed on two representative databases (Pubmed, Google Scholar), the Erowid Center website (a US non-profit educational organization that provides information about psychoactive plants and chemicals), and various governmental websites. The terms used for the database search were "mephedrone", "methylone", "new psychoactive substances", "synthetic cathinones", "substituted cathinones", "substance abuse", "substance use disorder", "adverse effects", "fatalities". The literature search was limited to years 2005-2015 and led to the identification of 71 potentially relevant articles. To date, the actual prevalence rates of their use remains difficult to estimate. Important health-related issues have emerged in relation to the somatic, psychiatric, and addictive consequences of their use. The potential chronic health effects of their prolonged use remain to date unknown (e.g., reproductive toxicity, genotoxicity and carcinogenic potential). Treatment for patients with prolonged exposure to synthetic cathinones should ideally include a drug management plan coupled with psychotherapy taking place in a structured program of care.

Genetics and psychotic disorders: A fresh look at consanguinity.

Consanguineous unions refer to marriages between related individuals who share a common ancestor. These unions are still commonplace in certain regions of the world such as the southern coast of the Mediterranean, throughout the Middle East and South-East Asia. According to available data, couples of second cousins or closer and their offspring currently represent 10.4% of the world's population, thus resulting in increased frequencies of autosomal recessive disorders. Furthermore, consanguinity may be implicated in the increased frequency of multifactorial pathologies such as mental disorders. The few existing epidemiological studies in consanguineous and/or geographically isolated populations confirm that there is a significant association between consanguinity and mental disorders and a higher risk of schizophrenia or bipolar disorders among offspring from consanguineous couples. There exists a strong and complex genetic component in the predisposition to psychotic disorders that has been confirmed in numerous studies. However, the genetic basis of these disorders remains poorly understood. GWAS studies (Genome Wide Association Studies) over the past 10 years have identified a few weak associations, thus refuting the "common diseases-common variants" hypothesis. A model implicating numerous rare variants has been supported by the recent discovery of CNVs (Copy Number Variants) and their statistically significant association with psychiatric disorders such as schizophrenia, bipolar disorders and autism. The study of consanguineous families may contribute to identifying rare variants in homogenous populations who have conserved certain alleles. Major developments in molecular biology techniques would facilitate these studies as well as contributing to identifying major genes. These results emphasize the need for genetic counseling in high-risk communities and the importance of implementing preventive actions and raising awareness concerning the risk of consanguineous unions.

Smoker's identity scale: Measuring identity in tobacco dependence and its relationship with confidence in quitting.

BACKGROUND AND OBJECTIVES: Persistent smoking behaviours are associated with numerous motives, explaining the absence of a single treatment for quitting. One of these motives may include that of identification. The threat of losing their smoker's identity may represent a significant obstacle to lasting abstinence. The objective of this study is to design a specific identity questionnaire and examine correlations between the degree of smoking identity and persistent smoking. METHODS: Patients attending a smoking cessation seminar completed the Modified Reasons for Smoking Scale, Barriers to smoking cessation checklist and our 6-item Smoker's Identity Scale (SIS) (n = 170 questionnaires). RESULTS: SIS showed good internal consistency, calculated by a Chronbach test (α = .785) with no redundant questions. There was a correlation between strong tobacco dependence (measured by the Fagerström questionnaire) and strong smoking identity (p = .0001). Strong identity was associated with less confidence in quitting at both 1 and 6 months (p = .037 and p = .002, respectively). We showed that identity represents an obstacle to quitting in 32% of our patients and is associated with decreased confidence in quitting. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Our study shows that measuring identity in smokers who wish to make a quit attempt may help to identify specific obstacles to abstinence. This may also help in elaborating improved quitting strategies and patient management. Further research is necessary to confirm these results.

Self-medication of achalasia with cannabis, complicated by a cannabis use disorder.

Achalasia is a rare esophagus motility disorder. Medical, endoscopic and surgical treatments are available, but all endorse high relapse rates. No data has been published to date reporting a therapeutic effect of cannabis use neither in achalasia nor on its influence on manometric measurements. We report the case of a patient diagnosed with achalasia. He could benefit from a large panel of therapeutic interventions, but none of them was effective over the time. He first used cannabis at age 20 and identified benefits regarding achalasia symptoms. He maintained regular moderate cannabis use for 9 years, with minimal digestive inconvenience. A manometry performed without cannabis premedication was realized at age 26 and still found a cardiospasm. Cannabis use could explain the gap between functional symptoms assessment and manometry measurement. Further investigations are warranted to explore a therapeutic effect of cannabis in achalasia and possible influence on outcome measurements.

[Therapeutic use of cannabis derivatives]. / Usage thérapeutique des dérivés du cannabis.

The therapeutic use of cannabis has generated a lot of interest in the past years, leading to a better understanding of its mechanisms of action. Countries like the United States and Canada have modified their laws in order to make cannabinoid use legal in the medical context. It's also the case in France now, where a recent decree was issued, authorizing the prescription of medication containing "therapeutic cannabis" (decree no. 2013-473, June 5, 2013). Cannabinoids such as dronabinol, Sativex and nabilone have been tested for the treatment of acute and chronic pain. These agents are most promising to relieve chronic pain associated with cancer, with human immunodeficiency virus infection and with multiple sclerosis. However, longer-term studies are required to determine potential long-term adverse effects and risks of misuse and addiction.

A damage/benefit evaluation of addictive product use.

AIMS: To obtain damage/benefit assessments of eight commonly used addictive products and one addictive behaviour from French addiction experts and link these to overall evaluations. DESIGN AND SETTING: Criteria-based evaluation by experts in addiction. Specific statistical modelling to estimate the relative contribution of various criteria to formulating expert general opinion on products. PARTICIPANTS: Forty-eight French experts in addiction. MEASUREMENTS: Twelve criteria covering the whole spectrum of damages and benefits to users and to society evaluated using visual analogue scales (VAS). Direct measure of expert overall subjective opinions on products from user and from social perspectives. FINDINGS: Damage scoring identified alcohol (damage score = 48.1), heroin (damage score = 44.9) and cocaine (damage score = 38.5) as the most harmful products to users and to society; gambling was considered the least harmful (score = 22.5), replicating previous results. Damage scoring correlated poorly with legal status or with overall subjective expert opinions of products. Benefit perception scores indicated alcohol as a clear outlier (benefit score = 45.5) followed by tobacco (benefit score = 34.3) and cannabis (benefit score = 31.1). Statistical modelling suggested that experts attributed 10 times more importance to benefit perception than to damages when making their subjective opinion from a user perspective and two times more importance to benefit perception than to damages in formulating their opinion from a social perspective. CONCLUSIONS: The perceived benefits of addictive products appear to have a major impact on the opinion of those products expressed by a number of French addiction experts.

Striatal and extrastriatal dopamine transporter in cannabis and tobacco addiction: a high-resolution PET study.

The dopamine (DA) system is known to be involved in the reward and dependence mechanisms of addiction. However, modifications in dopaminergic neurotransmission associated with long-term tobacco and cannabis use have been poorly documented in vivo. In order to assess striatal and extrastriatal dopamine transporter (DAT) availability in tobacco and cannabis addiction, three groups of male age-matched subjects were compared: 11 healthy non-smoker subjects, 14 tobacco-dependent smokers (17.6 ± 5.3 cigarettes/day for 12.1 ± 8.5 years) and 13 cannabis and tobacco smokers (CTS) (4.8 ± 5.3 cannabis joints/day for 8.7 ± 3.9 years). DAT availability was examined in positron emission tomography (HRRT) with a high resolution research tomograph after injection of [11C]PE2I, a selective DAT radioligand. Region of interest and voxel-by-voxel approaches using a simplified reference tissue model were performed for the between-group comparison of DAT availability. Measurements in the dorsal striatum from both analyses were concordant and showed a mean 20% lower DAT availability in drug users compared with controls. Whole-brain analysis also revealed lower DAT availability in the ventral striatum, the midbrain, the middle cingulate and the thalamus (ranging from -15 to -30%). The DAT availability was slightly lower in all regions in CTS than in subjects who smoke tobacco only, but the difference does not reach a significant level. These results support the existence of a decrease in DAT availability associated with tobacco and cannabis addictions involving all dopaminergic brain circuits. These findings are consistent with the idea of a global decrease in cerebral DA activity in dependent subjects.

Pharmacological treatments of opiate dependence.

Opiate substitution therapies have largely contributed to improving outcomes in opiate dependent patients. Their impact has significantly diminished HIV transmission rates, decreased incidence of overdose and reduced delinquency due to heroin trafficking. Since then, some advances have been made in the formulations and dosing regimen of these treatments. They have also largely facilitated opiate withdrawal. However, concerning the maintenance of opiate abstinence, very few new treatments have been proposed. Despite considerable advances in our knowledge of the neurobiological mechanisms of opiate dependence, few clinical trials have been proposed to test new molecules both in accompanying opiate substitution and in maintaining abstinence from illicit opiate use. The objective of this article is to examine the evidence concerning the treatment of opiate dependent patients, especially new treatments and to examine the eventual gaps between currently knowledge, available treatment and demands.

Association of inflammation genes with alcohol dependence/abuse: a systematic review and a meta-analysis.

The aim of the present work was to systematically review all association studies of inflammation genes with alcohol dependence/alcohol abuse (AD/AA) and to perform a meta-analysis. Odds ratios (ORs) were estimated by contrasting the ratio of counts of the 'high-risk' versus 'low-risk' alleles in AD/AA cases versus controls. Data reported in at least three published studies were available for four genetic polymorphisms [TNF-α-238 (rs361525, G/A); TNF-α-308 (rs1800629, G/A); IL-1RA (VNTR [86 bp]n); IL-10-592 (rs1800896, C/A)]. In total, nine meta-analyses were performed. Of these, only the TNF-α-238 polymorphism showed a significant association with AD/AA (OR=1.36, 95% CI: 1.05-1.76). This risk remained significant and increased slightly when we considered only patients with advanced alcohol-related liver disease (AALD) (OR=1.5, 95% CI: 1.13-1.98) but not when we considered only patients without AALD (OR=1.08, 95% CI: 0.5-2.35). Sensitivity analysis showed that this genetic association is derived from the AALD phenotype rather than from AD. Our approach is limited by our phenotype definition; some studies included chronic heavy drinkers (minimal daily consumption of 80 g for a minimal duration of 10 years) but without a standardized psychiatric assessment.