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Background: people suffering from substance use disorders (SUD) often die by suicide, so that the prevention of suicide attempts (SA) remains a top priority in this population. SA recurrence is common and is associated with suicide death, but this phenotype has been overlooked in SUD populations. Thus, we aimed at identifying the risk factors of SA recurrence in SUD, controlling for both gender and levels of exposure to addictive substances, including tobacco.Methods: we consecutively recruited 433 treatment-seeking outpatients with either opiate or cocaine use disorder and assessed their lifetime history of addictive and suicidal symptoms by standardized questionnaires. They were reliably classified as never, single or recurrent (≥ 2) suicide attempters, whose characteristics were identified by multinomial regression, stratified by gender; and compared to our previous work on serious SA in order to identify common or different risk profiles.Results: 86/140 (61%) suicide attempters reported recurrence. The mean number of SA was 3.1. Recurrence was independently associated with psychiatric hospitalization in both genders, with nicotine dependence in men and with sedative use disorders in women.Limitations: psychiatric diagnoses were derived from the current medication regimen.Conclusion: specific and possibly avoidable/treatable risk factors for the recurrence of SA in SUD have been identified for the first time, opening new avenues for research and prevention in this high-risk population. Apart from nicotine dependence, these risk factors were very similar to those of serious SA. Although this comparison is indirect for now, it suggests a common liability towards suicidal behavior. [ABSTRACT FROM AUTHOR]

Abstract: Staff members of psychiatric facilities are at high risk of secondhand smoking. Smoking exposure was assessed in 41 nonsmoking employees of a psychiatry department before and after a ban. Subjective exposure measures decreased in 76% of the subjects. Salivary cotinine decreased in the subsample of seven subjects with high pre-ban levels (32±8 vs 40±17ng/ml, p =.045). [Copyright &y& Elsevier]

Abstract: Addiction to drugs is an important public health concern. Describing the frequency of dependence, abuse and use of substances in a country allows a monitoring and helps in the design of an appropriate healthcare system. We will present studies describing the prevalence of use of tobacco, alcohol, and illicit drugs in France, with a comparison to European or International studies. They show a decrease in the use of tobacco and cannabis, while there is an increase in alcohol use in young adults. We also observe that the difference in substances use between females and males is tightening, especially in young people. We have less studies of analytic epidemiology trying to describe risk or protective factors associated with substances’ use in France. Further studies on addicted people''s pathway (from use to abuse and to dependence, as well as from dependence to recovery, with or without medical support) are warranted. [Copyright &y& Elsevier]

Objectives: Bipolar Disorder (BD) is frequently comorbid with other psychiatric disorders. However, few studies systematically examine which disorders are more likely to occur pre- or post-BD onset. We examine the prevalence and Age At Onset (AAO) of psychiatric conditions in adults with BD.Methods: A structured clinical interview was used to assess lifetime history and AAO of alcohol and cannabis misuse, suicide attempts, anxiety and eating disorders in a French sample of euthymic patients with BD (n = 739). Regression analyses were used to test for statistically significant associations between rates and AAO of comorbidities in BD groups stratified by sex or subtype.Results: Prevalence of alcohol and cannabis misuse was associated with male sex and BD-I subtype; whilst most anxiety and eating disorders were associated with female sex. The AAO of most comorbid conditions preceded that of BD, except for panic disorder, agoraphobia and alcohol misuse. Few variations were observed in AAO of comorbidities according to groups.Limitations: All assessments were retrospective, so estimates of prevalence rates and especially exact AAO of some comorbidities are at risk of recall bias.Conclusions: Sex and BD subtype are associated with different rates of comorbid disorders. However, there were minimal between group differences in median AAO of comorbidities. By describing the chronological sequence of comorbidities in BD we were able to demonstrate that a minority of comorbidities typically occurred post-onset of BD. This is noteworthy as these disorders might be amenable to interventions aimed at early secondary prevention. [ABSTRACT FROM AUTHOR]

Abstract: Cocaine is known to induce stereotyped movements and psychotic symptoms. We measured stereotyped movements in a clinical sample of 89 cocaine addicts in an outpatient setting with the cocaine induced-psychosis (CIP) questionnaire. The rate of lifetime stereotyped behaviour associated with cocaine use was 67.4%. They were more severe in cocaine injectors. [Copyright &y& Elsevier]

Rationnel La méthadone est prescrite comme traitement de substitution de la dépendance aux opiaces depuis les années 1960 [1] . Néanmoins, l’expérience des cliniciens montre que la réponse thérapeutique est obtenue à des doses extrêmement variables d’un patient à l’autre et qu’il est également difficile de prédire les effets secondaires. Méthode En collaboration avec plusieurs centres de soins d’Île-de-France (CSAPA Espace Murger, AP–HP, hôpital Fernand-Widal, Dr Gaël Dupuy ; clinique Liberté, hôpital Paul-Guiraud, Dr Didier Touzeau ; CSAPA Moreau de Tours, centre hospitalier Sainte-Anne, Dr Xavier Laqueille ; CSAPA Monte Cristo, AP–HP, HEGP, Dr Cyrille Orizet ; CSAPA EGO, association Aurore, Dr Philippe Coeuru ; ECIMUD, AP–HP, hôpital Louis-Mourier, Dr Anne-Marie Simonpoli ; CSAPA 110 Les Halles, PSA 75, Dr Pierrre Polomeni ; Bus Méthadone Gaia, Dr Elisabeth Avril) nous avons conduit une étude recueillant des données cliniques et génétiques chez des patients héroïnomanes stabilisés sous traitement par méthadone. Résultats Deux cent seize patients ont été inclus entre 2008 et 2013. Nous présenterons ici des résultats concernant la prédiction des doses nécessaires à l’équilibre thérapeutique chez 80 patients ayant complété une hospitalisation de jour comprenant une exploration fonctionnelle du métabolisme hépatique [2] . Nous présenterons également des résultats sur 161 patients ayant bénéficié d’une mesure de l’espace Qt par un cardiologue et du recueil de facteurs de risque cliniques et génétiques de Torsades de pointes, complétant des données préliminaires que nous avons publié [3] . Ces résultats permettront de discuter les données à recueillir pour une prescription optimisée de méthadone à l’heure de la médecine personnalisée. [ABSTRACT FROM AUTHOR]

Introduction: Methadone, a Mu-opioid receptor agonist, is currently used as a maintenance treatment in opioid dependant patients. However, its therapeutic index is narrow, and side effects are life threatening. Non-optimal dosing results in withdrawal symptoms and further heroin craving and use. The optimal dose is defined as the dose necessary to obtain a stable substitution. This optimal maximal dose can then be decreased, the final goal being to stop substitution. Objectives: To identify factors to optimize the methadone optimal daily dose. Aims: We aimed to identify genetic variants (SNP) associated with the methadone optimal dose. In a candidate gene approach, we focused on OPRM1, which encodes the opioid receptor Mu, and on DRD2/ANKK1 SNP''s, implied in the reward dopaminergic signalling. Methods: Caucasians patients (n=98) followed for methadone maintenance treatment were included in this prospective study. Candidate SNPs were genotyped (ANKK1: TaqI A; DRD2: c.957C>T; OPRM1: c.A118G). The plasmatic methadone level was determined using mass spectrometry in 59 patients. Results: Two polymorphisms were significantly associated to the optimal methadone doses: OPRM1 c.A118G (p=0.03) and DRD2 TaqI A (p=0.035). The TaqIA polymorphism is located within ANKK1, which encodes a serine threonine kinase which role remains elusive. Its molecular link to methadone pharmacodynamy remains to be established. None of these polymorphisms was associated neither to the current methadone doses, nor to the methadone plasmatic concentration. Conclusion: This description is the first step to optimize the prescription of methadone in caucasian populations. [Copyright &y& Elsevier]

Introduction: Mephenesin is a central muscle relaxant, acting through a depression of the activity of some neurones in the caudate nucleus. It was proposed as a potential treatment of alcohol withdrawal syndrome in the 50s. This over the counter medicine is now mainly prescribed to treat spasticity or as an adjunctive treatment of painful muscle spasm. We know little about this substance except that side effects are venous thrombosis, haemolysis or cutaneous intolerance. Yet, no case of abuse or dependence has been reported. Aims: To report a series of 5 clinical cases in patients who developed abuse or dependence to mephenesin. Methods: We performed a systematic search in data bases of both Paris addictovigilance and poison centres from 1999 to 2010. Clinical details were obtained from clinicians when possible. A literature search was also performed to describe mephenesin mechanisms of actions that could be implied. Results: Three (3) women et 2 men aged 35 to 52 years (m : 43.6) were identified as abusing mephenesin, among which 4 patients had a full DSM IV criteria of dependence. All had a previous history of abuse or substance dependence (alcohol, heroin, codeine, ketamine…).The average mephenesin daily intake was 13g (9 to 24g) when the maximum recommended dosage is 3gr/d. In one case, a withdrawal syndrome was observed (tremor, aggressiveness). Conclusion: Mephenesin may be abused by patients with previous risk factors, especially a personal history of alcohol dependence. [ABSTRACT FROM AUTHOR]

Aims: Animal studies suggest that in alcohol withdrawal the balance of neurotransmitters gamma aminobutyric acid (GABA) and glutamate is altered. To test this in humans, we aimed to measure plasma levels of glutamate, GABA and glutamate/GABA ratio in alcoholic patients presenting with complicated AWS with the same values in non-alcohol abuser/dependent controls and to determine prognostic factors for severe withdrawal. Methods: 88 patients admitted to the emergency room for acute alcohol intoxication (DSM-IV) were prospectively included. Measurements of GABA and glutamate were performed on admission (Time 1, T1) and after 12 ± 2 h (T2). The experimental group (EG) was composed of 23 patients who presented at T2 with a severe AWS. The control group (CG) consisted of healthy subjects paired with the EG (gender and age). Logistic regression was performed in order to compare associated clinical and biological variables that could predict severe withdrawal. Results: The concentration of GABA in the EG at T1 was significantly lower than that in the CG. The concentration of glutamate in the EG at T1 was significantly higher than that in the CG. The glutamate/GABA ratio in the EG at T1 was significantly higher than the ratio in the CG. With a multivariate logistic regression model, glutamate level at admission remained the only criterion identified as a predictor of AWS at 12 h. Conclusion: Decreased synthesis of GABA and increased synthesis of glutamate might be related to withdrawal symptoms experienced on brutal cessation of chronic alcohol intake. [ABSTRACT FROM AUTHOR]

Aims: Animal studies suggest that in alcohol withdrawal the balance of neurotransmitters gamma aminobutyric acid (GABA) and glutamate is altered. To test this in humans, we aimed to measure plasma levels of glutamate, GABA and glutamate/GABA ratio in alcoholic patients presenting with complicated AWS with the same values in non-alcohol abuser/dependent controls and to determine prognostic factors for severe withdrawal. Methods: 88 patients admitted to the emergency room for acute alcohol intoxication (DSM-IV) were prospectively included. Measurements of GABA and glutamate were performed on admission (Time 1, T1) and after 12 ± 2 h (T2). The experimental group (EG) was composed of 23 patients who presented at T2 with a severe AWS. The control group (CG) consisted of healthy subjects paired with the EG (gender and age). Logistic regression was performed in order to compare associated clinical and biological variables that could predict severe withdrawal. Results: The concentration of GABA in the EG at T1 was significantly lower than that in the CG. The concentration of glutamate in the EG at T1 was significantly higher than that in the CG. The glutamate/GABA ratio in the EG at T1 was significantly higher than the ratio in the CG. With a multivariate logistic regression model, glutamate level at admission remained the only criterion identified as a predictor of AWS at 12 h. Conclusion: Decreased synthesis of GABA and increased synthesis of glutamate might be related to withdrawal symptoms experienced on brutal cessation of chronic alcohol intake. [ABSTRACT FROM AUTHOR]

Background: Suicide is a major public health concern and suicide attempts (SA) are frequent and burdensome in people suffering from substance use disorders (SUDs). In particular, serious SAs are a preoccupying form of attempt, which remain largely overlooked in these populations, especially regarding basic risk factors such as gender, addictive comorbidity and substance use patterns. Thus, we undertook a gender-specific approach to identify the risk factors for serious SAs in outpatients with multiple SUDs.Material and Methods: 433 Treatment-seeking outpatients were consecutively recruited in specialized care centers and reliably classified as serious, non-serious and non-suicide attempters. We also characterized lifetime exposure to SUDs, including tobacco smoking, with standardized instruments. Current medication, including psychotropic treatments were collected, which informed psychiatric diagnoses. Multinomial regression identified independent factors specifically associated with serious SAs in each gender, separately.Results: 32% Participants (N=139, 47% Women and 27% Men) reported lifetime SA. There were 82 serious attempters (59% of attempters), without significant gender difference. Sedative dependence was an independent risk factor for serious SA compared to non-SA in Women and compared to non-serious SA in Men, respectively. Other risk factors included later onset of daily tobacco smoking in Men and history of psychiatric hospitalizations in Women, whose serious SA risk was conversely lower when reporting opiate use disorder or mood disorder, probably because of treatment issues.Conclusions: Despite several study limitations, we identified subgroups for a better-tailored prevention of serious SAs among individuals with SUDs, notably highlighting the need to better prevent and treat sedative dependence. [ABSTRACT FROM AUTHOR]

Compulsive behavior is a core symptom of both obsessive compulsive disorder (OCD) and cocaine addiction (CA). Across both pathologies, one can identify a priori goal-directed actions (purportedly anxiolytic checking or washing in OCD and pleasure-seeking drug use in addiction) that turn into rigid, ritualized and repetitive behaviors over which the patient loose control. One possible psychopathological mechanism underlying compulsivity is behavioral inflexibility, namely a deficit in the aptitude to dynamically adapt to novel contexts and changing reward rules. The probabilistic reversal learning paradigm allows to objectively assess behavioral flexibility by challenging participants with a task where they have to learn through trials-and-errors which of two stimuli is the most-often rewarded one, while adjusting to sudden inconspicuous contingency reversals. We therefore hypothesized that both OCD and CA would be associated with impaired cognitive flexibility, as measured through perseverative response rate following contingency reversals in this task. Interestingly, impulsivity may also be assessed within this task via the tendency of participants to switch from one stimulus to the other following probabilistic errors. To investigate cognitive inflexibility in relation to CA and OCD respectively, we first compared the performance in a probabilistic reversal learning task of cocaine users, ex cocaine users (abstinent for 2 months or more), and controls, as well as that of participants from the general population whose obsessive-compulsive traits were assessed using the OCI-R, a well-validated self-questionnaire. Our task yielded results similar to those found in the literature: cocaine addicts changed their responses more often, and learned less effectively. Ex-cocaine addicts performed better than addicts but worse than controls, suggesting that addicts’ poor results may be in part explained by reversible cognitive consequences of addiction. Addicts with less cognitive impairments may also be less likely to relapse. Regarding the relationship of flexibility to subclinical OCD traits, we found no link between OCI-R score and perseveration, or between impulsiveness and excessive switching. [ABSTRACT FROM AUTHOR]

Tonically active cholinergic interneurons (TANs) from the nucleus accumbens (NAc) are centrally involved in reward behavior. TANs express a vesicular glutamate transporter referred to as VGLUT3 and thus use both acetylcholine and glutamate as neurotransmitters. The respective roles of each transmitter in the regulation of reward and addiction are still unknown. In this study, we showed that disruption of the gene that encodes VGLUT3 (Slc17a8) markedly increased cocaine self-administration in mice. Concomitantly, the amount of dopamine (DA) release was strongly augmented in the NAc of VGLUT3−/− mice because of a lack of signaling by metabotropic glutamate receptors. Furthermore, dendritic spines and glutamatergic synaptic transmission on medium spiny neurons were increased in the NAc of VGLUT3−/− mice. Increased DA and glutamate signaling in the NAc are hallmarks of addiction. Our study shows that TANs use glutamate to reduce DA release and decrease reinforcing properties of cocaine in mice. Interestingly, we also observed an increased frequency of rare variations in SLC17A8 in a cohort of severe drug abusers compared with controls. Our findings identify VGLUT3 as an unexpected regulator of drug abuse. [ABSTRACT FROM AUTHOR]

Contexte Dans une cohorte de patients traités par méthadone, nous avons retrouvé 35 % de tentatives de suicide (TS) sur la vie, 53 % un trouble anxieux et 61 % un trouble de l’humeur. Presque tous étaient fumeurs quotidiens de tabac, les trois quart avaient soit une dépendance au cannabis, à l’alcool ou à la cocaïne associée sur la vie. Dans ce contexte, l’identification de facteurs de variabilité interindividuelle de sévérité et de comorbidité pourrait prédire le risque d’évolution péjorative chez les sujets jeunes ou moins comorbides. Outre les traumas dans l’enfance [1] , les styles parentaux [2] semblent avoir un rôle important dans ces trajectoires, tout comme un âge de début (ADD) plus précoce des consommations de substances [3] . Objectif/méthodes Nous avons ainsi recherché chez 85 patients stabilisés sous méthadone des associations entre les scores à la Measure of Parental Style (MOPS) [4] (séparés pour chaque parent) et l’ADD de tabac, alcool, cannabis, sédatifs et cocaïne ainsi que la présence de comorbidités addictives. Les caractéristiques sociodémographiques, les conduites suicidaires et les comorbidités addictives et psychiatriques (DSM IV) étaient évaluées par entretien semi-structuré. Résultats Nous avons retrouvé des associations significatives ( p < 0,00625) après corrections de Bonferroni pour huit tests effectués) entre indifférence paternelle et ADD inférieur du tabac, et entre abus maternel et ADD inférieur des sédatifs, mais pas entre MOPS et présence d’un TA comorbide. Après ajustement sur âge, sexe, dépression majeure et troubles anxieux en régression linéaire, l’abus maternel restait prédictif d’un ADD plus précoce des sédatifs (bêta = –0,24, p = 0,039), tout comme la dépression (bêta = –0,24, p = 0,045). Discussion Malgré des limites dues à notre évaluation rétrospective et à la faible taille de l’échantillon, ces résultats soulignent l’importance de l’environnement précoce dans la variabilité des trajectoires addictives. Cela suggère l’intérêt d’une prévention primaire chez des patients jeunes présentant ces dysfonctionnements parentaux. [ABSTRACT FROM AUTHOR]

La littérature suggère qu’une enfance instable engendrerait une résilience plus faible, et qu’une résilience faible serait prédictrice d’un plus haut risque de dépendance et de complications psychiatriques [1,2] . Dans ce contexte, notre objectif a été d’étudier l’ensemble de ces facteurs en une même étude afin d’affiner les trajectoires des patients consommateurs de cocaïne. Nous avons réalisé une étude préliminaire sur 200 patients régulièrement suivis dans 6 centres de soin parisiens. Nous avons évalué la résilience à l’aide de la CD-RISC [3] qui est un auto-questionnaire en 25 questions évaluant 5 dimensions et donnant lieu à un score total. De plus, nous avons procédé à des hétéro-évaluations concernant les variables psychiatriques et les antécédents familiaux (évalués rétrospectivement) et mesuré les dépendances aux différentes substances à l’aide des critères du DSM-IV. Les facteurs de vulnérabilité nous montrent que l’abus (ou dépendance) d’alcool du père, ainsi que le nombre de ruptures parentales sont associés à une plus faible résilience. L’étude des variables psychiatriques révèle qu’une faible résilience serait associée à un plus haut risque de commettre au moins une tentative de suicide dans sa vie, à un plus haut risque d’hospitalisation en service de psychiatrie et de diagnostic de schizophrénie. S’agissant des comorbidités addictives, une faible résilience est prédictrice d’un plus haut risque de dépendance aux opiacés, ainsi qu’aux benzodiazépines, et d’injection de cocaïne. Enfin, les facteurs du CD RISC sont associés à plus de sevrages hospitaliers. En reprenant la théorie de Didier, les adolescents s’intègrerait dans un groupe de pairs dépendants pour palier à une cellule familiale insecure [2] . Une faible résilience de ces patients pourrait conduire à plus de dépendance aux produits anesthésiants comme stratégie de coping . Pour aller plus loin, il pourrait être pertinent d’étudier conjointement résilience, traumatismes et style parentaux. [ABSTRACT FROM AUTHOR]

Introduction: Cocaine users often experience transient psychotic symptoms following cocaine use (Smith et al. 2009). The severity of such psychotic symptoms is influenced by cocaine dose (Vorspan et al. 2011). Several authors observed a higher prevalence of childhood trauma in cocaine addicts than control subjects (Enoch et al. 2010). Objective: Describe cocaine induced psychosis and evaluate if it is associated with childhood trauma. Aim: Define the population of cocaine users who experiment cocaine induced psychotic symptoms. Method: We did a transversal retrospective study. 100 outpatient cocaine users were evaluated with Scale for the Assessment of Positive Symptoms of Crack Induced Psychosis (SAPS-CIP) and Childhood Trauma Questionnaire (CTQ). Informations were obtained about lifetime cocaine use (age of onset, DSM IV dependence criteria, route of administration, daily dose, days of use per month). Results: We did not observe any link between SAPS-CIP and CTQ or CTQ and cocaine consumption. About cocaine consumption, more often patients took cocaine during the worst period, higher is the SAPS-CIP score. If patients are (or were) dependent to cocaine, they have higher scores on SAPS-CIP. Moreover, if patients took cocaine intravenously, they have higher scores on SAPS-CIP than if they took it by snorting, or smoking. Conclusion: In the conditions of our study, childhood trauma isn’t a mediator for cocaine induced psychosis. About psychotic symptoms, they seem to be more severe among daily cocaine dependents who take it intravenously. [Copyright &y& Elsevier]

Introduction: Withdrawal syndrome occurs in 50% of cannabis dependant patients. In our clinical practice, we observed that few patients recognize and attribute abstinence symptoms to cannabis cessation. Insight or awareness of cannabis dependence remains poorly studied. Objectives: We propose to study the relationship between insight and cannabis withdrawal syndrome. Our hypothesis is that patients showing a higher score on a cannabis withdrawal scale would have a higher score on an insight scale. Methods: We recruited 35 cannabis dependent outpatients between October 2008 and April 2009 in an addiction clinic. Insight of cannabis dependance was assessed with the insight Q8 scale ranging [0–8]. We designed a cannabis withdrawal scale by checking DSM V withdrawal symptoms, and each symptom was retrospectively scored by an analogue scale (from 0 to 5). Correlation between insight and withdrawal scores was calculated using Spearman''s ρ. Results: Sex ratio was 2.5. Mean age was 35.9±1.4 years. Most patients (85.7%) reported at least one withdrawal symptom. Sleep disturbances (95.8%) and craving (75.8%) were the most frequent. Mean score of insight was of 4.2±0.4 points. The intensity of withdrawal syndrome and insight score were positively correlated (ρ=0.594, p<0.001). Conclusion: Our results show an association between experiencing more withdrawal symptoms and insight or awareness of cannabis dependence. These results could be used in the treatment of cannabis dependent patients. [Copyright &y& Elsevier]

Introduction: Impulsivity and decision making are impaired in cocaine addicts. However, most studies were performed in the USA. Objectives: To assess impulsivity and decision making in a sample of French cocaine addicts. Methods: Subjects: 40 current cocaine addicts and 21 control subjects with no history of drug abuse were compared using the Barratt Impulsiveness Scale (BIS) and Iowa Gambling Task (IGT). Subjects from the cocaine addicted group were evaluated for cocaine craving with the Obessive Compulsive Cocaine Scale (OCCS), and for their pattern of use. Statistical analysis: The mean scores of impulsivity and decision making were compared in the two groups (Mann-Whitney U test). In the group of 40 cocaine addicts, clinical factors that could be associated with high impulsivity and poor decision making scores were tested (Spearman’ s rho, Chi-square and Mann-Whitney U tests). Result: Compared to controls, cocaine addicts had a higher impulsivity score (BIS: 72±11 vs 57±8, U=138, p<.001) and had more disadvantageous choices on the decision making test (IGT) (advantageous minus disadvantageous choices -4 ±19 vs 24±35, U=234, p=.005). There was a significant correlation between high impulsivity scores on the BIS and high cocaine craving as well as heavy cocaine use (more than 4 times a week). No correlation was found between poor decision making and high craving or frequent cocaine use. Discussion: The discrepancy between impulsivity and poor decision making in cocaine addicts is discussed. [ABSTRACT FROM AUTHOR]