Antipsychotic drug dose in real-life settings results from a Nationwide Cohort Study.

Despite national and international recommendations and while there is no evidence for increased efficacy of higher doses, several studies suggested that the prescribed doses in routine practice are higher than the maximal recommended doses in 20-40% of schizophrenia patients worldwide. METHODS: the aims of the present study were: (1) to describe the patterns of antipsychotic daily dose prescriptions in routine clinical practice in a large and representative cohort of French schizophrenia patients and, (2) to study the characteristics of patients receiving higher doses. RESULTS: in all cases, regardless of the antipsychotic treatment used, the average dose was greater than 1.0 defined daily dose (DDDeq), which is the average recommended dose. For SGA, the mean DDDeq ranged from 1.2 for aripiprazole to 1.6 for olanzapine and clozapine, respectively. For a given patient, the mean ± S.D. total daily cumulative dose (TCD) of antipsychotic was 1.9 ± 2.4 DDDeq. A "high dose" was defined as a TCD ≥ 1.5 DDDeq, 789 (45.2%) patients received a "high dose". Patients in the "high dose" group were more frequently suffering from a more severe paranoid schizophrenia, had more often a comorbid antisocial personality disorder and/or a substance use disorder. CONCLUSIONS: the present study suggests that in France, antipsychotic drugs doses prescribed by psychiatrists are higher, compared to other countries. All recommendations agree on the fact that the preferential dose should be the "minimum-effective" dose. Optimizing prescribing practices would be important to optimize the benefit/risk ratio and to minimize the risks side effects.

[The concept of paedophilia. Part 2: Etiologies, forensic aspects and therapeutic options]. / Le concept de pédophilie. Partie 2 : Hypothèses étiologiques, aspects médico-légaux et stratégies thérapeutiques.

Paedophilia is a paraphilia characterised by behaviour, drives or sexual fantasies that are intense and recurring and that generally involve children. This sexual deviation is often linked to personal distress, to a significant alteration of personal, family, professional and social life, in a general sense. In our modern Western societies, paedophilia and the perversions associated with it are punishable by law. Paedophilia is a concept that is very ancient, complex and particularly diverse in its many clinical presentations. Its societal impact is very important and contrasts with the real knowledge of this issue among non-specialists, or even among specialists. In this second part of the article, the authors will develop the aetiologies of paedophilia, the therapeutic options and the forensic aspects.

La pédophilie est une paraphilie caractérisée par des comportements, des pulsions ou des fantasmes sexuels intenses et récurrents qui impliquent, de manière générale, les enfants. Cette déviance sexuelle s'accompagne souvent d'une souffrance personnelle, d'une altération significative du fonctionnement personnel, familial, professionnel et, au sens large, social. Dans nos sociétés occidentales modernes, la pédophilie et les perversions s'y rapportant sont condamnées par la loi. La pédophilie est un concept très ancien, complexe et surtout hétérogène. Son impact sociétal est très important et contraste avec le degré de connaissance réel de cette déviance parmi les non spécialistes et même parmi les spécialistes. Dans la seconde partie de cet article, les auteurs vont développer les hypothèses étiologiques, les principales options thérapeutiques et quelques aspects médico-légaux.

[The concept of paedophilia. Part 1 : Historical background and nosology]. / Le concept de pédophilie. Partie 1: Historique et nosologie.

Paedophilia is a paraphilia characterised by behaviour, drives or sexual fantasies that are intense and recurring and that involve children, in a general sense. This sexual deviation is often linked to personal distress, to a significant alteration of personal, family, professional and social life, in a general sense. In our modern Western societies, paedophilia and the perversions associated with it are punishable by law. Paedophilia is a concept that is very ancient, complex and particularly diverse in its many clinical presentations. Its societal impact is very important and contrasts with the real knowledge of this issue among non-specialists, or even among specialists. Based on expert clinical experience gathered at the courts and on an exhaustive review of current literature on the subject, the authors propose an update of the concept of paedophilia. In the first part of this work, the authors will discuss several aspects such as the historical background and the clinical aspects and nosography of paedophilia. This literature review will be accompanied by short clinical vignettes, based on the authors' clinical experience.

La pédophilie est une paraphilie caractérisée par des comportements, des pulsions ou des fantasmes sexuels intenses et récurrents qui impliquent, de manière générale, les enfants. Cette déviance sexuelle s'accompagne souvent d'une souffrance personnelle, d'une altération significative du fonctionnement personnel, familial, professionnel et, de manière générale, social. Dans nos sociétés occidentales modernes, la pédophilie et les perversions s'y rapportant sont condamnées par la loi. La pédophilie est un concept très ancien, complexe et surtout hétérogène. Son impact sociétal est très important et contraste avec le degré de connaissance réel de cette déviance parmi les non-spécialistes et même parmi les spécialistes. En se basant sur une expérience clinique d'expert auprès des tribunaux et sur une revue exhaustive de la littérature actuelle, les auteurs proposent une actualisation du concept de pédophilie. Cette revue de littérature sera accompagnée de courtes vignettes cliniques issues de l'expérience clinique des auteurs.

[Psychopathological consequences of confinement]. / Conséquences psychopathologiques du confinement.

The psychological effects of isolation have already been described in the literature (polar expeditions, submarines, prison). Nevertheless, the scale of confinement implemented during the COVID-19 pandemic is unprecedented. In addition to reviewing the published studies, we need to anticipate the psychological problems that could arise during or at a distance from confinement. We have gone beyond the COVID-19 literature in order to examine the implications of the known consequences of confinement, like boredom, social isolation, stress, or sleep deprivation. Anxiety, post-traumatic stress disorder, depression, suicidal or addictive behaviours, domestic violence are described effects of confinement, but the mechanisms of emergence of these disorders and their interrelationships remain to be studied. For example, what are the mechanisms of emergence of post-traumatic stress disorders in the context of confinement? We also remind the reader of points of vigilance to be kept in mind with regard to eating disorders and hallucinations. Hallucinations are curiously ignored in the literature on confinement, whereas a vast literature links social isolation and hallucinations. Due to the broad psychopathological consequences, we have to look for these various symptoms to manage them. We quickly summarize the diagnostic and therapeutic approaches already in place, such as telemedicine, which is undergoing rapid development during the COVID-19 crisis.

CASE-REPORT Case study of a patient presenting both type II bipolar affective disorder and Klinefelter syndrome.

Klinefelter syndrome (KS) is the most common sex chromosomal disorder with an estimated prevalence of 1 in 500-1000. Increased incidences of anxiety, depression, substance abuse, psychotic and behavioral disorders, and sexual disorders have been reported in patients with KS. The aim of this case study was to report a case of a man with untreated KS who was also diagnosed with type II bipolar disorder. This case report raises awareness regarding psychiatric diagnoses that may be associated with such a highly prevalent condition. A 46-year-old man who had previously been diagnosed with an untreated KS was examined in our Psychiatric Department with an acute hypomanic episode. Clinical improvement was observed within 4 days and psychiatric symptoms were resolved in 7 days without use of medication. A psychiatric history of a depressive episode and at least two hypomanic episodes, as well as a family history of two relatives diagnosed with bipolar disorder, strongly suggest that our patient has type II bipolar disorder. Bipolar disorder may be a comorbid disorder in patients with KS. Routine screening for mood disorders and appropriate referral and evaluation should be performed. Future genetic research is warranted to explore why some chromosomal abnormalities (e.g., duplications), especially those located on the X chromosome, such as Klinefelter syndrome, may be associated with a bipolar or psychotic disorder in some individuals but not in others.

[Consequences of tobacco, cocaine and cannabis consumption during pregnancy on the pregnancy itself, on the newborn and on child development: A review]. / Conséquences potentielles de la consommation de tabac, de cannabis et de cocaïne par la femme enceinte sur la grossesse, le nouveau-né et l'enfant : revue de littérature.

BACKGROUND: Substance use has increased worldwide. Based on these data, we may think that substance use has also increased during pregnancy, but epidemiological data are scarce in this population. The potential consequences of tobacco, cocaine or cannabis use during pregnancy are a major public health concern. The combined use of different substances during pregnancy may have serious consequences on the pregnancy and on child development. METHODS: In this paper, we will describe the potential consequences for the newborn, child and adolescent after being exposed to tobacco, cannabis and cocaine in utero. For this purpose, we will review all retrospective and prospective studies (in English and French) referenced in PubMed reporting on the somatic or psychiatric consequences of alcohol, tobacco and drug consumption by pregnant women on newborn and children. Consumption during pregnancy was assessed in these studies using simple questionnaires, biomarkers analysis or both. RESULTS: Generally speaking, these pregnancies are at high risk for both the mother and the foetus: for example, an increased risk of miscarriage or of reduced length of gestation, an increased risk of uterine apoplexy and placenta praevia, more premature births and/or hypotrophy were reported. The occurrence of a newborn's withdrawal syndrome may be misdiagnosed. Many consequences on child development may be observed such as growth disorders, learning or motor disorders, language disorders, cognitive disorders (attention, memory, executive functions), attention deficit disorders with impulsivity or with hyperactivity (ADHD), and memory disorders. The prevalence of depressive or anxiety disorders may also be increased in these children. The risk of addictive disorders or schizophrenia in children exposed in utero to illicit drugs or tobacco is still unknown. The combined use of different substances increases, consequently it is difficult to disentangle the consequences on child development of each of the drugs used during pregnancy owing to potential interactions between these drugs. The consequences on child development will also depend on the dose and on the time of drug use during pregnancy. DISCUSSION: The National Institute of Drug Abuse reported that 75% of the infants exposed in utero to one or more substances will present medical problems during childhood, as compared to only 27% of the non-exposed infants. However, the medical consequences are still a matter of controversies. Methodological biases, such as the use of different rating scales among studies, and the heterogeneity of the populations included are main limitations. Further studies are needed using larger cohorts and longer follow-up periods.

[Assessment of a new law for sex offenders implemented in France in 1998]. / Loi du 17 juin 1998 : bilan de l'expérience des médecins coordonnateurs de Haute Normandie.

OBJECTIVES: Most people recognize that incarceration alone will not solve sexual violence. Treating the offenders is critical in an approach to preventing sexual violence and reducing victimization. The Law of June 17, 1998, on the prevention and repression of sexual offences, as well as the protection of minors, makes a provision for the possibility of medical and psychological monitoring adapted to these particular individuals. Sex offenders may well be constrained, after their incarceration, to social and judicial follow-up, which may include coerced treatment in order to reduce the risk of recidivism. In order to control this follow-up, the legislature has created the position of medical coordinator, who acts as an interface between justice and care in conjunction with the treating physician. This study is the first attempt to evaluate the activity of physician coordinators conducted in France since the implementation in 2004 of the 1998 law on monitoring sex offenders. METHODS: An interview of all the physician coordinators in Upper Normandy was conducted. The files of all sex offenders subjected to coerced treatment were studied. RESULTS: In our sample of 100 sex offenders who were subjected to coerced treatment (any kind of treatment) (99% men, 60% of sexual assaults on minors, 14% of cases of indecent exposure), minor victims of sexual assault were: 78% females; in 90% of cases the victim was aged under 14 years (under 10 in 52% of cases), 60% of cases were intrafamilial incest; the victim was an unknown aggressor in only one case out of 60. The constraint follow-up contributed to reducing the risk of recidivism (three cases of recidivism in 100 individuals over an average duration of follow-up of five years), although it remains difficult to assess the recidivism over a duration of time as short as five years. A diagnosis of paraphilia was only applied in 19% of cases (in 10 cases pedophilia, exhibitionism in nine cases). Only six subjects were receiving antiandrogen treatment. A diagnosis based on Axis I DSM was established in 57% of cases. Personality disorders were mentioned in the medical records in 65% of cases. An antisocial personality disorder was not prominent (20%). In 56 cases, the individuals had been victims of physical, psychological or sexual abuse. Nearly half of the individuals had a past history of sexual or non sexual offences, among those, 16 subjects had previously been convicted at least three times. The seniority of the prior conviction was more than 10 years in 43% of cases. Physician coordinators interviewed were satisfied with their work and felt they had contributed to improving the care of patients who had committed sexual offences. CONCLUSION: However, this study shows the need to create a national reference centre, which could enable a multidisciplinary evaluation of difficult cases and could also boost the development of research in this area where many questions remain unanswered, particularly regarding the determinants of deviant sexual behaviour and risk factors for recidivism.

Chemical sex (chemsex) in a population of French university students.

Introduction: Chemsex is defined by the use of psychoactive substances to facilitate or improve sexual relations. Our objectives were to assess the prevalence of the practice of 'chemsex' in a population of French university students and to identify socio-demographic and clinical factors associated with this practice. Material and methods: We have used an anonymous online questionnaire comprising 15 questions on socio-demographic characteristics, chemsex use, sexual satisfaction, the type of substances used in this sexual context and their route of administration. Results: A total of 680 people were included in our study. Among them, 22.5% reported chemsex behaviour in the past year. Using a multivariate analysis, factors associated with chemsex were dating application use (p = 0.049) and pornography use [viewing more than once per month (p = 0.002)]. Having a sexual partner involved in chemsex (p < 0.0001), celibacy (p = 0.007), sexual orientations other than heterosexual (p = 0.0013) and especially bisexuality (p = 0.0002) were also significantly associated with chemsex. Conclusion: This is the first study reporting a high prevalence of chemsex in a university student population. Further larger studies should be conducted to confirm these results showing a high prevalence of this at-risk behaviour.

Safety of sertindole versus risperidone in schizophrenia: principal results of the sertindole cohort prospective study (SCoP).

OBJECTIVE: To explore whether sertindole increases all-cause mortality or cardiac events requiring hospitalization, compared with risperidone. METHOD: Multinational randomized, open-label, parallel-group study, with blinded classification of outcomes, in 9858 patients with schizophrenia. RESULTS: After 14147 person-years, there was no effect of treatment on overall mortality (sertindole 64, risperidone 61 deaths, Hazard Ratio (HR) = 1.12 (90% CI: 0.83, 1.50)) or cardiac events requiring hospitalization [sertindole 10, risperidone 6, HR = 1.73 (95% CI: 0.63, 4.78)]: Of these, four were considered arrhythmia-related (three sertindole, one risperidone). Cardiac mortality was higher with sertindole (Independent Safety Committee (ISC): 31 vs. 12, HR=2.84 (95% CI: 1.45, 5.55), P = 0.0022; Investigators 17 vs. 8, HR=2.13 (95% CI: 0.91, 4.98), P = 0.081). There was no significant difference in completed suicide, but fewer sertindole recipients attempted suicide (ISC: 68 vs. 78, HR=0.93 (95% CI: 0.66, 1.29), P = 0.65; Investigators: 43 vs. 65, HR=0.67 (95% CI: 0.45, 0.99), P = 0.044). CONCLUSION: Sertindole did not increase all-cause mortality, but cardiac mortality was higher and suicide attempts may be lower with sertindole.

[Psychoactive substance use during pregnancy: a review]. / Etat des lieux de la consommation de substances psychoactives par les femmes enceintes.

All around the world, the potential consequences of the increasing use of psychoactive substances during pregnancy are a major public health concern. It is estimated that 20 to 30% of pregnant women use tobacco, 15% use alcohol, 3 to 10% use cannabis and 0.5 to 3% use cocaine. The estimation of tobacco consumption during pregnancy is better known as compared with alcohol and substance use prevalence during pregnancy, which remains under estimated or unknown. For example, in France, the prevalence of cannabis and cocaine use during pregnancy is unknown. In general, the prevalence of drug or alcohol use during pregnancy is estimated by extrapolating data from epidemiological studies conducted in the general population (in France or in other countries). However, drug or alcohol use in the general population may dramatically vary from one country to another. Even if some studies have reported the prevalence of alcohol or substance use in different countries around the world, most of them were based on the mother's interview. In most cases, the mother did not report exactly the amount of drugs or alcohol used. Further studies measuring alcohol or substance use in the mother's blood, hair or in the newborn's meconium are needed. In addition, different methodologies have been used in the literature (different types of interview, with or without biological measurements; different subjects included (in- or out-pregnant women, psychiatric comorbidities or not, different economic status, etc). Despite these methodological biases, the prevalence of drug or alcohol use increases in pregnant women, and in most cases, several drugs are associated. Most of the studies have used structured or semi-structured interviews such as the addiction severity index (ASI) or the alcohol use disorders identification test (AUDIT) to assess alcohol or drug consumption. In addition, the identification of risk factors for substance or alcohol use during pregnancy would allow the early detection of these high-risk pregnancies. Environmental factors such as low economic status or marital status may play an important role. Personality disorders may also contribute to substance or alcohol use during pregnancy. In fact, in most studies the quality of the obstetrical survey is lower in pregnant women using drugs or alcohol but it remains difficult to describe a specific at-risk profile in these pregnant women. Consumption of alcohol or of one or more psychoactive substances during pregnancy may have serious consequences on the pregnancy and on the child's development. Fetal alcoholism syndrome is the main etiology of mental retardation in France. We need to improve our knowledge of alcohol and substance use during pregnancy in order to target information for prevention campaigns and to implement specific mother and child medical care in high-risk populations.

Proposed diagnostic criteria for apathy in Alzheimer's disease and other neuropsychiatric disorders.

There is wide acknowledgement that apathy is an important behavioural syndrome in Alzheimer's disease and in various neuropsychiatric disorders. In light of recent research and the renewed interest in the correlates and impacts of apathy, and in its treatments, it is important to develop criteria for apathy that will be widely accepted, have clear operational steps, and that will be easily applied in practice and research settings. Meeting these needs is the focus of the task force work reported here. The task force includes members of the Association Française de Psychiatrie Biologique, the European Psychiatric Association, the European Alzheimer's Disease Consortium and experts from Europe, Australia and North America. An advanced draft was discussed at the consensus meeting (during the EPA conference in April 7th 2008) and a final agreement reached concerning operational definitions and hierarchy of the criteria. Apathy is defined as a disorder of motivation that persists over time and should meet the following requirements. Firstly, the core feature of apathy, diminished motivation, must be present for at least four weeks; secondly two of the three dimensions of apathy (reduced goal-directed behaviour, goal-directed cognitive activity, and emotions) must also be present; thirdly there should be identifiable functional impairments attributable to the apathy. Finally, exclusion criteria are specified to exclude symptoms and states that mimic apathy.

[Self-mutilating behaviour: a study on 30 inpatients]. / Les conduites automutilatrices: étude portant sur 30 patients.

INTRODUCTION: Deliberate self-injury is defined as the intentional, direct injuring of body tissue without suicidal intent. There are different types of deliberate self-mutilating behaviour: self cutting, phlebotomy, bites, burns, or ulcerations. Sometimes, especially among psychotic inpatients, eye, tongue, ear or genital self-mutilations have been reported. In fact, self-mutilation behaviour raises nosological and psychopathological questions. A consensus on a precise definition is still pending. Many authors consider self-mutilating behaviour as a distinct clinical syndrome, whereas others hold it to be a specific symptom of borderline personality disorder. Self-mutilating behaviour has been observed in 10 to 15% of healthy children, especially between the age of 9 and 18 months. These self mutilations are considered as pathological after the age of 3. Such behaviour is common among adolescents, with a higher proportion of females, and among psychiatric inpatients. Patients use different locations and methods for self-mutilation. Deliberate self harm syndrome is often associated with addictive behaviour, suicide attempt, and personality disorder. CLINICAL MATERIAL: We report on an observational study including 30 inpatients and we compared the data with the existing literature. As a matter of fact, until now, most of the papers deal with case reports or with very specific patterns of self-mutilation (eye, tongue or genital self-mutilations). Otherwise, papers report the relationships between self-mutilation and somatic or personality disorders (Lesh Nyhan syndrome, borderline personality disorder, dermatitis artefacta, self-mutilation in children following brachial plexus related to birth injury, mental retardation...). Our study included all self harmed patients who had been admitted to our psychiatric hospital (whatever the location and type of self-mutilation). Patients suffering from brain injury or mental retardation were excluded. RESULTS: In our sample, there was a higher percentage of women (29 women and 1 man) and the mean age was 18 (12 to 37). More than half of the patients were aged under 18. Single parent families were reported in 30% of cases. Thirty percent of patients had been physically or sexually abused during childhood. Sixty percent had a comorbid psychiatric disorder, 63% had been hospitalised previously (half of them twice or more). Seventy-three percent of patients had previously attempted suicide (notably deliberate self-poisoning and cutting) that was not considered as self-mutilating behaviour by the patients themselves. Each patient had self harmed themselves at least twice and most often different methods and locations were used (deliberate self harm of forearms 90%, thighs 26.7%, legs 16.7%, chest 10%, belly 10%, hands 6.9%, face 6.9%, arms 6.7%, and feet 3.3%). Addictive disorders, such as substance abuse (tobacco 46.7%; alcohol 23.3%; illicit drugs 16.7% mostly cannabis or cocaine) and eating disorders (33.3% and among them 50% of cases were restrictive anorexia nervosa) were often associated with a deliberate self harm syndrome. Three psychiatric diagnoses were often observed in our cohort: depressive disorder 36.7%; personality disorder 20%; psychosis 10% and depressive disorder associated with personality disorder 33.3%. In our sample, psychotic patients differed on several clinical aspects: the atypical location (abdomen, nails) and method (needles) of self-mutilating behaviour. None of them had been abused during childhood and none was suffering from addictive disorders.

[Renal transplantation, anxiety and depressive disorders and quality of life]. / Transplantation rénale, troubles anxiodépressifs et qualité de vie.

Until now there are few data in the literature describing psychiatric comorbidity in patients waiting for renal transplantation. We have conducted a cross sectional study estimating the prevalence of anxiety and depressive disorders in three groups of renal transplant patients, before transplantation, six months and one year after. The MINI was used to estimate the prevalence of anxiety and depressive disorders. Anxiety and depressive symptoms were assessed using the HAD. Patients' quality of life was also assessed using the SF-36. This study did not find any major impact of renal transplantation on the prevalence of structured psychiatric disorders. Indeed, the prevalence of depressive and anxiety disorders did not differ significantly between the three groups. The mean scores of anxiety did not differ significantly between the three groups in contrast to the mean scores of depression, which differed significantly between the group "before transplantation" and the group "one year after transplantation". We did not find any significant difference concerning the scores of patient's quality of life between the three groups, except for the item "health perceived by the patients themselves". Health perceived by the patients was greater in the group "after transplantation". The quality of life of dialysed or transplant patients was strongly correlated with anxiety and depressive symptoms scores, emphasizing the major interest of a multidisciplinary approach for these patients.

The pathophysiological mechanisms of motivational deficits in Parkinson's disease.

Parkinson's disease (PD) is a progressive degenerative disorder that leads to disabling motor symptoms and a wide variety of neuropsychiatric symptoms. Apathy is the most common psychiatric disorder in the early stages of untreated PD and can be defined as a hypodopaminergic syndrome, which also includes anxiety and depression. Apathy is also considered the core feature of the parkinsonian triad (apathy, anxiety and depression) of behavioural non-motor signs, including a motivational deficit. Moreover, apathy is recognised as a distinct chronic neuropsychiatric behavioural disorder based on specific diagnostic criteria. Given the prevalence of apathy in approximately 40% of the general Parkinson's disease population, this appears to be a contributing factor to dementia in PD; also, apathy symptoms are factors that potentially contribute to morbidity, leading to a major impairment of health-related quality of life, thus stressing the importance of understanding the pathophysiology of this disease. Several studies have clearly established a prominent role for DA-mediated signals in PD apathy. However, synergistic interaction between dopaminergic impairment resulting from the neurodegenerative process and deep brain stimulation of the subthalamic nucleus may cause or exacerbate apathy. Furthermore, serotoninergic mechanism signalling is also likely to be of importance in this pathophysiology.

[Pulmonary mucormycosis: difficulties in diagnosis and treatment]. / Mucormycoses pulmonaires: difficultés diagnostiques et thérapeutiques.

INTRODUCTION: Mucormycosis is a rare opportunistic fungal infection due to filamentous fungi of the order Mucorales in the class Zygomycetes. Rhino-cerebral and pulmonary manifestations predominate on account of the airborn spread of the spores. Gastro-intestinal, cutaneous and disseminated disease is less common. The principal risk factors are immuno-suppression and diabetic keto-acidosis. CASE REPORTS: One case of fatal pulmonary mucormycosis and two cases of colonisation illustrate both the extreme severity of this disease and the diagnostic difficulties facing the physician. The ubiquitous nature of the organism leads to frequent colonisation and, moreover, the symptomatology readily mimics that of invasive pulmonary aspergillosis. The diagnosis of mucormycosis can only be confirmed by pathological and mycological examination of biopsy specimens. These requirements conflict with the need for urgent treatment with surgical debridement, amphotericin B and control of the underlying pathology. Sadly the mortality remains very high, between 50 and 80% in published series. CONCLUSION: Currently there is hope of new therapeutic approaches with posaconozole but the ineffectiveness of voriconozole and the echinocandines, used more and more against aspergillus, raises the possibility of an increase in mucormycosis by selection.

To what extent is it possible to dissociate the anxiolytic and sedative/hypnotic properties of GABAA receptors modulators?

The relatively common view indicates a possible dissociation between the anxiolytic and sedative/hypnotic properties of benzodiazepines (BZs). Indeed, GABAA receptor (GABAAR) subtypes have specific cerebral distribution in distinct neural circuits. Thus, GABAAR subtype-selective drugs may be expected to perform distinct functions. However, standard behavioral test assays provide limited direction towards highlighting new action mechanisms of ligands targeting GABAARs. Automated behavioral tests, lack sensitivity as some behavioral characteristics or subtle behavioral changes of drug effects or that are not considered in the overall analysis (Ohl et al., 2001) and observation-based analyses are not always performed. In addition, despite the use of genetically engineered mice, any possible dissociation between the anxiolytic and sedative properties of BZs remains controversial. Moreover, the involvement the different subtypes of GABAAR subtypes in the anxious behavior and the mechanism of action of anxiolytic agents remains unclear since there has been little success in the pharmacological investigations so far. This raises the question of the involvement of the different subunits in anxiolytic-like and/or sedative effects; and the actual implication of these subunits, particularly, α-subunits in the modulation of sedation and/or anxiety-related disorders. This present review was prompted by several conflicting studies on the degree of involvement of these subunits in anxiolytic-like and/or sedative effects. To this end, we explored the GABAergic system, particularly, the role of different subunits containing synaptic GABAARs. We report herein the targeting gene encoding the different subunits and their contribution in anxiolytic-like and/or sedative actions, as well as, the mechanism underlying tolerance to BZs.

5-HT2C receptors in psychiatric disorders: A review.

5-HT2Rs have a different genomic organization from other 5-HT2Rs. 5HT2CR undergoes post-transcriptional pre-mRNA editing generating diversity among RNA transcripts. Selective post-transcriptional editing could be involved in the pathophysiology of psychiatric disorders through impairment in G-protein interactions. Moreover, it may influence the therapeutic response to agents such as atypical antipsychotic drugs. Additionally, 5-HT2CR exhibits alternative splicing. Central serotonergic and dopaminergic systems interact to modulate normal and abnormal behaviors. Thus, 5HT2CR plays a crucial role in psychiatric disorders. 5HT2CR could be a relevant pharmacological target in the treatment of neuropsychiatric disorders. The development of drugs that specifically target 5-HT2C receptors will allow for better understanding of their involvement in the pathophysiology of psychiatric disorders including schizophrenia, anxiety, and depression. Among therapeutic means currently available, most drugs used to treat highly morbid psychiatric diseases interact at least partly with 5-HT2CRs. Pharmacologically, 5HT2CRs, have the ability to generate differentially distinct response signal transduction pathways depending on the type of 5HT2CR agonist. Although this receptor property has been clearly demonstrated, in vitro, the eventual beneficial impact of this property opens new perspectives in the development of agonists that could activate signal transduction pathways leading to better therapeutic efficiency with fewer adverse effects.

Spasticity in disorders of consciousness: a behavioral study.

BACKGROUND: Spasticity is a frequent complication after severe brain injury, which may impede the rehabilitation process and diminish the patients' quality of life. AIM: We here investigate the presence of spasticity in a population of non-communicative patients with disorders of consciousness. We also evaluate the correlation between spasticity and potential factors of co-morbidity, frequency of physical therapy, time since insult, presence of pain, presence of tendon retraction, etiology and diagnosis. DESIGN: Cross-sectional study. SETTING: University Hospital of Liège, Belgium. POPULATION: Sixty-five patients with chronic (>3 months post insult) disorders of consciousness were included (22 women; mean age: 44±14 y; 40 with traumatic etiology; 40 in a minimally conscious state; time since insult: 39±37 months). METHODS: Spasticity was measured with the Modified Ashworth Scale (MAS) and pain was assessed using the Nociception Coma Scale-Revised (NCS-R). RESULTS: Out of 65 patients, 58 demonstrated signs of spasticity (89%; MAS≥1), including 40 who showed severe spasticity (61.5%; MAS≥3). Patients with spasticity receiving anti-spastic medication were more spastic than unmedicated patients. A negative correlation was observed between the severity of spasticity and the frequency of physical therapy. MAS scores correlated positively with time since injury and NCS-R scores. We did not observe a difference of spasticity between the diagnoses. CONCLUSION: A large proportion of patients with disorders of consciousness develop severe spasticity, possibly affecting their functional recovery and their quality of life. The observed correlation between degrees of spasticity and pain scores highlights the importance of pain management in these patients with altered states of consciousness. Finally, the relationship between spasticity and treatment (i.e., pharmacological and physical therapy) should be further investigated in order to improve clinical care. CLINICAL REHABILITATION IMPACT: Managing spasticity at first signs could improve rehabilitation of patients with disorders of consciousness and maximize their chances of recovery. In addition, decreasing this trouble could allow a better quality of life for these non-communicative patients.

SPEM impairment in drug-naive schizophrenic patients: evidence for a trait marker.

Smooth-pursuit eye movements (SPEM) were assessed in healthy subjects and in drug-naive, chronic, and residual schizophrenic patients. SPEM gain was found to be decreased in all the schizophrenic patients who also exhibited a significant increase in the rate of saccades. The frequency of square-wave jerks was the same in schizophrenic patients and normal controls, suggesting that the primary abnormality in schizophrenic patients was a low gain rather than a defect of the saccadic system. Patients were retested 1 month later, and stability of gain was high even in formerly drug-naive subjects who had been treated for 1 month with neuroleptic drugs. Altogether these results confirm the conclusions of most previous studies, extend them to drug-naive schizophrenic patients, and favor the hypothesis that SPEM impairment is a trait marker in schizophrenia.