Bruno Millet

Prevalence of smoking in psychiatric patients

Compelling evidence that tobacco-smoking is a form of drug addiction exists. The aim of this study is to determine the following: (1) prevalence of tobacco-smoking and of nicotine dependence in French psychiatric patients; (2) rates and patterns of tobacco smoking and of nicotine dependence according to diagnosis; (3) relationship between current smoking status and antipsychotic medications; and (4) relationship between cigarette smoking and neurological side effects induced by neuroleptics. A population of 711 psychiatric in- and outpatients was assessed using: (1) a detailed smoking self-questionnaire for smoking history and nicotine dependence; and (2) a questionnaire for staff covering treatments and DSMIII-R diagnoses. Data were analyzed using chi2 analysis of variance (ANOVA) tests (one factor) for quantitative comparisons between groups of patients, and analysis of covariance (ANCOVA) test with age covariate was performed for age-dependent variables. Prevalence of smoking in the population of psychiatric patients was significantly higher than in the French general population. Diagnoses among current smokers were mainly substance-related disorder and schizophrenia. The authors established correlations between prevalence of smoking and age, sex, marital and socioeconomic status, alcohol use, coffee consumption and other psychoactive substance use or abuse. The authors did not find relationship between smoking prevalence and institutionalization. Neuroleptic neurological side effects were significantly fewer among smokers compared to nonsmokers. However, the rate of smokers was significantly higher in psychiatric patients receiving neuroleptic drugs. Nicotine abuse in psychiatric patients, and especially in schizophrenic patients, could support the hypothesis that smoking is consistent with self-medication.

5HTTLPR polymorphism in schizophrenic patients: Further support for association with violent suicide attempts

Previous studies testing the functional polymorphism in the promoter of the serotonin‐transporter gene (5HTTLPR) in various psychiatric conditions have suggested that the association could be with an intermediate phenotype, impulsivity and/or violence rather than with a diagnosis. Schizophrenia is associated with a high risk of suicide, especially in patients with high impulsivity. We examined whether this polymorphism could be associated with violent suicide and/or impulsivity in schizophrenic patients. We genotyped the 5HTTLPR polymorphism in 185 unrelated schizophrenic patients from a French Caucasian population. The genotype frequencies significantly differed between patients who made violent suicide attempts and both, those who attempted suicide with a non‐violent method (P = 0.013) and those who never attempted suicide (P = 0.026). The genotypes containing the low activity “short” allele was significantly more frequent in violent suicide attempters (P = 0.007) than in non‐violent suicide attempters. No evidence was found for an association either with schizophrenia itself, when compared to gender and ethnically matched controls (n = 159) or with impulsivity, assessed using Barratts Impulsivity Scale. Although replication studies are warranted, these results in schizophrenia further support the hypothesis that 5HTTLPR polymorphism is a risk factor for violent suicidal behavior.

Prospects for anxiolytic therapy: a reflection from different viewpoints

Abstract Benzodiazepines are the most commonly used and effective treatment of symptoms of anxiety, but they have drawbacks. The current challenge is to discover partial agonists that do not cause the adverse effects characteristic of benzodiazepines. The authors discuss the main drugs that are used in the treatment of acute anxiety and some of the current or future alternatives and also highlight several problems that need to be resolved in the development of new anxiolytics.

1 – Place de la chimiothérapie dans les stratégies thérapeutiques des troubles psychiatriques

L’avènement de la psychiatrie biologique constitue une des avancées majeures de notre spécialité au cours des soixante dernières années. L’utilisation de la chlorpromazine (1954-1956) a réduit la souffrance de milliers de patients hospitalisés depuis de longues années en hôpital psychiatrique. Les conséquences spectaculaires en termes d’atténuation des troubles du comportement, de diminution de l’agressivité, de disparition de la symptomatologie délirante ont contribué à modifi er les opinions sur la nature de la maladie psychiatrique. Les principales classes de psychotropes se sont ainsi développées, révolutionnant l’évolution et le pronostic des grandes maladies mentales, le psychiatre hospitalier passant en un siècle d’un rôle de taxinomiste à celui d’authentique thérapeute. La connaissance des propriétés pharmacologiques des substances a largement contribué à l’émergence d’hypothèses étiopathogéniques pour les principales pathologies : • action antidopaminergique centrale des neuroleptiques à l’origine de l’hypothèse de Carlson sur une hyperdopaminergie prévalente dans le déclenchement des productions délirantes du schizophrène, désormais à intégrer dans un déséquilibre de la balance dopaminergique entre excès de dopamine en région limbique et défi cit en région corticale préfrontale ; • action des antidépresseurs sur la neurotransmission ayant abouti à diverses hypothèses : catécholaminergique, sérotoninergique... dans les états dépressifs ; • action intracellulaire complexe du lithium sur le système second messager à l’origine de ses propriétés thymorégulatrices ; • action des anticomitiaux dans les troubles de l’humeur conduisant à l’extrapolation de leur effet antikindling dans l’épilepsie à une action assimilable dans la bipolarité. De telles découvertes ont une indéniable valeur heuristique : ainsi, la découverte de récepteurs spécifi ques et de ligands endogènes, à partir des propriétés anxiolytiques des benzodiazépines, a-t-elle favorisé la découverte de nouveaux principes actifs. De même, la mise au point d’un neuroleptique de troisième génération, agoniste partiel possédant une action sélective « région-dépendante » sur la dopamine traduit-elle le développement d’une psychopharmacologie de plus en plus sophistiquée. Au contraire, l’espoir 1