Franck J. Baylé

Efficacy of the novel antidepressant agomelatine on the circadian rest-activity cycle and depressive and anxiety symptoms in patients with major depressive disorder: a randomized, double-blind comparison with sertraline.

OBJECTIVE This study evaluates the efficacy of agomelatine, the first antidepressant to be an agonist at MT(1)/MT(2) receptors and an antagonist at 5-HT(2C) receptors, versus sertraline with regard to the amplitude of the circadian rest-activity cycle and depressive and anxiety symptoms in patients with major depressive disorder (MDD). METHOD Outpatients with DSM-IV-TR-defined MDD received either agomelatine 25 to 50 mg (n = 154) or sertraline 50 to 100 mg (n = 159) during a 6-week, randomized, double-blind treatment period. The study was conducted from 2005 to 2006. The main outcome measure was the relative amplitude of the individual rest-activity cycles, expressed as change from baseline to week 6 and collected from continuous records using wrist actigraphy and sleep logs. Secondary outcome measures were sleep efficiency and sleep latency, both derived from actigraphy, and efficacy on depression symptoms (17-Item Hamilton Depression Rating Scale total score and Clinical Global Impressions scale scores) and anxiety symptoms (Hamilton Anxiety Rating Scale total score and subscores). RESULTS A significant difference in favor of agomelatine compared to sertraline on the relative amplitude of the circadian rest-activity cycle was observed at the end of the first week (P = .01). In parallel, a significant improvement of sleep latency (P <.001) and sleep efficiency (P <.001) from week 1 to week 6 was observed with agomelatine as compared to sertraline. Over the 6-week treatment period, depressive symptoms improved significantly more with agomelatine than with sertraline (P <.05), as did anxiety symptoms (P <.05). CONCLUSIONS The favorable effect of agomelatine on the relative amplitude of the circadian rest-activity/sleep-wake cycle in depressed patients at week 1 reflects early improvement in sleep and daytime functioning. Higher efficacy results were observed with agomelatine as compared to sertraline on both depressive and anxiety symptoms over the 6-week treatment period, together with a good tolerability profile. These findings indicate that agomelatine offers promising benefits for MDD patients. TRIAL REGISTRATION www.isrctn.org: ISRCTN49376288.

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.

Inattentive Symptoms of ADHD Are Related to Evening Orientation.

Objective: Morningness is a stable characteristic of individuals, related to impulsivity and novelty seeking. The evening orientation is a risk factor for psychiatric conditions such as depression and personality disorders. The authors hypothesized that adults suspected of having ADHD are more evening oriented than adults without ADHD. Method: Exploratory factor analyses were performed on the polychoric correlation matrices of the full Adult Self-Report Scale for ADHD (ASRS) and the Composite Scale of Morningness (CSM). Results: As expected, two factors for the ASRS—Inattention and Impulsivity— Hyperactivity—and three factors for the CSM were retrieved. All three CSM factors correlated negatively with ASRS Inattention, none with ASRS Impulsivity—Hyperactivity. Conclusion: Inattention is more strongly related to eveningness than is Impulsivity—Hyperactivity, and therefore eveningness may constitute an endophenotype of the predominantly inattentive subtype of ADHD. These findings need to be replicated in a patient population with a standardized assessment of sleep quality.

Understanding impulsivity in severe depression? A psychometrical contribution

BACKGROUND Depression, especially severe depression, is strongly associated with suicidality. Impulsivity is one of the main dimensions of suicidality. The objective of this study was to assess the structure of impulsivity in severe depression and its relationships to suicide attempts. METHODS 127 depressed in-patients were assessed at admission and after 4 weeks of treatment for depression and impulsivity with the Impulsivity Rating Scale (IRS) and the Impulse Control Scale (ICS) or the Baratt Impulsivity Scale (BIS). RESULTS Three dimensions of impulsivity were evidenced in these severely depressed patients, i.e., behavioral loss of control, nonplanning and cognitive. These three dimensions are state dependent. Recent suicide attempts in severe depression are related to loss of control and cognitive impulsivity but not to nonplanning. IRS ad ICS may assess primarily behavioral impulsivity, i.e., loss of control and nonplanning, whereas BIS may assess primarily cognitive impulsivity. CONCLUSIONS In the future, these three dimensions should be correlated to biological and genetic markers of impulsivity [serotonergic (5-HT) system] and prospective studies should assess the predictive value of the three dimensions of impulsivity in the occurrence of suicide attempts in depressed patients.

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.

Clinical features of panic attacks in schizophrenia.

Since reports have underscored that panic attacks (PA) may be an identifiable state occurring in schizophrenia, we studied the symptomatology of PA in a group of schizophrenic patients. Of 40 patients (21 males and 19 females) attending a clinic for maintenance therapy of schizophrenia, 19 (36.8%) had a lifetime history of PA. Seven among those 19 patients (36.8%) had or had had spontaneous panic attacks, not related to phobic fears or delusional fears, and for the 12 remaining patients, the PA were related to paranoid ideas. Moreover, the paranoid subtype of schizophrenia tends to be more often associated with a history of panic attack than other subtypes of schizophrenia (52.6% vs 23.8%; chi2 = 3.5, P =.06). It seems that there are at least two types of PA in schizophrenic patients. The first one could be independent from the psychotic feature, with no psychopathological link. The second kind of PA could be directly related to a schizophrenic disorder, and found in patients with the paranoid subtype.

Cross-cultural study of the impulsiveness-venturesomeness-empathy questionnaire (IVE-7)

The construct of impulsivity has gained interest in the last decades, and has been developed from different theoretical positions. Among these, the Eysencks proposed a specific self-administered questionnaire (IVE-7) for measuring two components, Impulsiveness (IMP) and Venturesomeness (VENT), which are included within their psychoticism-extraversion-neuroticism (P-E-N) system of personality. In the current study, the IVE-7 was translated into French and back-translated into English. Students filled out the French version, and data were analyzed for males and females separately. The scales reliabilities are similar between languages for IMP and VENT. The exploratory factor analyses revealed two acceptable three-factor solutions, although they failed to clearly identify the third factor. The factor similarity between genders was found very satisfactory using three different methods. The French and English factorial solutions also showed a very good level of similarity in each gender. Finally, the IMP was positively correlated with the Motor Impulsivity subscale of the Barratt Impulsivity Scale-10 (BIS-10) and with Dickmans Dysfunctional Impulsivity scale, and independent of the Spielberger Trait-Anxiety Inventory (TAI). We conclude that IMP and VENT are relatively stable between cultures and can be used reliably in French-speaking samples.

An aid for diagnosing attention-deficit/hyperactivity disorder at adulthood: psychometric properties of the French versions of two Wender Utah Rating Scales (WURS-25 and WURS-K).

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects up to 4% of the adults in the general population. The Utah criteria were devised in the 1970s to help a retrospective diagnosis of ADHD during childhood, a necessary but not sufficient condition for diagnosing ADHD at adulthood. A sample of 466 adults was collected from a referral center and a large university. We investigated the psychometric properties (reliability and factor structure) of the original WURS-25 and the WURS-K, two shortened versions of the Wender Utah Rating Scale. These scales have similar psychometric properties; both have a 3-factor structure with only the first two factors highly and positively correlated. The third factor in the WURS-K, antisocial behavior, is less specific to the construct of ADHD than the third factor in the WURS-25, mood/self-esteem. The 18-item Adult ADHD Self-Rating Scale (ASRS) was used as a screening tool for actual ADHD. The composite total scores and the factorial scores correlated moderately with ASRS total and subscores. Research is warranted to assess the cutoff scores against a diagnosis of ADHD using a structured interview.

Dépistage et prise en charge du trouble bipolaire : Résultats

La premiere strategie therapeutique recommandee est soit l’initiation en monotherapie d’un antipsychotique de seconde generation (AP2G) soit l’association d’un AP2G avec le lithium (Li) ou un anticonvulsivant (AC). Si vous decidez l’utilisation d’une monotherapie par AP2G : un delai avant reevaluation de 3 semaines vous est conseille ; • en cas d’absence d’efficacite, on vous recommande de • verifier l’observance, d’optimiser la posologie, et enfin d’associer un second SH.

Mechanisms of insight in schizophrenia and impact of cognitive remediation therapy.

The origins of poor insight in schizophrenia are still unclear. We contrasted the changes in clinical insight, basic cognitive processes, autobiographical memory and metacognition in 63 outpatients with schizophrenia pseudo-randomly assigned to one of three cognitive remediation groups: one targeting basic cognitive processes (RECOS), a second autobiographical memory (REMAu), and a third metacognitive deficits (MBCT). Three dimensions of insight (awareness of: mental illness, benefit of treatment, psychosocial consequences) improved after treatment, regardless of the group. In addition, the REMAu and MBCT showed an improvement on other dimensions of insight (symptomatic awareness and symptomatic attribution, respectively). Poor insight and its improvement after treatment were best predicted by a combination of basic cognitive, autobiographical and metacognitive measures. This study supports a multidimensional conception of insight and recommends the combination of remediation therapies to improve clinical insight in schizophrenia.