Patrice Boyer

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 Alzheimers 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 Alzheimers 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.

Common and distinct neural correlates of emotional processing in Bipolar Disorder and Major Depressive Disorder: A voxel-based meta-analysis of functional magnetic resonance imaging studies

Neuroimaging studies have consistently shown functional brain abnormalities in patients with Bipolar Disorder (BD) and Major Depressive Disorder (MDD). However, the extent to which these two disorders are associated with similar or distinct neural changes remains unclear. We conducted a systematic review of functional magnetic resonance imaging studies comparing BD and MDD patients to healthy participants using facial affect processing paradigms. Relevant spatial coordinates from twenty original studies were subjected to quantitative Activation Likelihood Estimation meta-analyses based on 168 BD and 189 MDD patients and 344 healthy controls. We identified common and distinct patterns of neural engagement for BD and MDD within the facial affect processing network. Both disorders were associated with increased engagement of limbic regions. Diagnosis-specific differences were observed in cortical, thalamic and striatal regions. Decreased ventrolateral prefrontal cortical engagement was associated with BD while relative hypoactivation of the sensorimotor cortices was seen in MDD. Increased responsiveness in the thalamus and basal ganglia were associated with BD. These findings were modulated by stimulus valence. These data suggest that whereas limbic overactivation is reported consistently in patients with mood disorders, future research should consider the relevance of a wider network of regions in formulating conceptual models of BD and MDD.

A double-blind comparison of sertraline and fluoxetine in the treatment of major depressive episode in outpatients

Depression is associated with considerable morbidity and mortality. As depressive disorders carry a high risk of relapse, treatment strategies include the use of a 6-month continuation period after resolution of the acute episode. Tolerability is of major importance when determining compliance and outcome during long-term therapy. Due to the superior tolerability profile of the selective serotonin reuptake inhibitors (SSRIs) over the older tricyclic antidepressants (TCAs), the former may be more suitable for extended therapy. Comparative studies have not shown differences between the SSRIs in terms of efficacy, but side-effect profiles may vary. A multicenter, double-blind, comparative study of sertraline and fluoxetine was carried out in outpatients fulfilling DSM-III-R criteria for major depressive disorder. Patients were randomised to receive sertraline (50-150 mg, n = 118) or fluoxetine (20-60 mg, n = 120) for 24 weeks. Assessments for depression (HAM-D, HAD, CGI-I, CGI-S), anxiety (Covi), sleep (Leeds Sleep Evaluation scale) and quality of life (SIP) were made at study entry and at weeks 2, 4, 8, 12, 18 and 24. All adverse events were recorded to allow evaluation of tolerability. In total, 88 patients in the sertraline group completed the study compared with 79 in the fluoxetine group. Side effects were responsible for the premature treatment withdrawal of seven (6%) sertraline patients and 12 (10%) fluoxetine patients. Two-hundred and thirty-four patients were included in an ITT analysis up to last visit (116 sertraline, 118 fluoxetine). At study endpoint, both treatments produced a significant improvement over baseline on all efficacy variables (P < 0.001). Although the magnitude of global changes in depression, anxiety, and quality of life was larger with sertraline than fluoxetine, none of the between-group differences reached statistical significance. However, significant differences in favour of sertraline were observed for individual HAM-D items including item 4 (insomnia onset) (P = 0.04), item 9 (agitation) (P = 0.02), and item 13 (general somatic symptoms) (P = 0.008). In addition, sertraline was associated with significantly superior performance on the Leeds Sleep Evaluation scale and on SIP items relating to sleep and rest, emotional behaviour and ambulation. Both sertraline and fluoxetine were well tolerated with no significant differences between treatments.

Functional and dysfunctional impulsivity: contribution to the construct validity

Objective: Impulsivity has been found to be an important trait of personality, whose consequences are not always negative although available questionnaires focused on its ‘dysfunctional’ aspect.

Clinical and Economic Comparison of Sertraline and Fluoxetine in the Treatment of Depression: A 6-Month Double-Blind Study in a Primary-Care Setting in France

SummaryIn a double-blind study in a primary-care setting in France, outpatients fulfilling DSM IV criteria for a major depressive episode were randomised to receive sertraline (50 to 150 mg/day; n = 122) or fluoxetine (20 to 60 mg/day; n = 120). Assessments, including clinical evaluation [Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global Impressions (CGI)] and quality of life [Functional Status Questionnaire (FSQ)], were made at study entry and after 4 and 6 months of treatment. Use of medical services, absences from work and productivity losses were recorded for calculation of direct and indirect costs from both the overall societal perspective and in terms of sickness insurance. In total, 231 patients (116 receiving sertraline, 115 receiving fluoxetine) were included in an intention-to-treat analysis assessed up to the last visit. Statistically significant clinical and quality-of-life improvements from baseline were observed in both treatment groups, with no between-group differences. Utilisation of medical resources was higher in fluoxetine-treated patients, with significantly more consultations with specialists. The 2 treatment groups were similar in terms of number of hospitalisations and duration of stay, whether related to depression or not. There were no significant differences between groups for work or productivity losses. Cost comparisons favoured sertraline treatment from both the societal (FF7780 vs FF8706) and sickness insurance (FF2936 vs FF3224) viewpoints, with cost differentials of FF926 and FF288, respectively. From the societal perspective, the total cost per patient over the 6-month course of the trial, irrespective of the study treatment given, was FF8241, and the corresponding sickness insurance cost was FF3079. At the time of the study, FF1 =

The composite scale of morningness: further psychometric properties and temporal stability.

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Anhedonia, Alexithymia and Locus of Control in Unipolar Major Depressive Disorders

OBJECT To assess the temporal stability of the French version of the Composite Scale of Morningness (CSM), and to replicate our previous findings in an independent sample in order to confirm the good internal properties of this instrument. METHOD Sixty nursing students (11 males and 49 females) filled out the Composite Scale of Morningness on two occasions over a 13-month period. RESULTS The scales reliability is high: Cronbachs alpha = 0.874 in males and 0.904 in females. The CSM total scores are normally distributed and independent of gender. They do not differ between occasions, and are highly correlated: r = +0.885 in males and r = +0.930 in females. CONCLUSION The French version of the CSM is stable over time and psychometrically reliable. These are the characteristics of a personality trait. Further studies should explore its personality, biological and genetic correlates.

Psychometric properties of the French version of the Composite Scale of Morningness in adults

The relationship between anhedonia, alexithymia and locus of control was studied in a group of healthy subjects (n = 56) and in a group of unipolar major depressives (n = 59). These dimensions were rated using the Physical Anhedonia Scale (PAS), the Toronto Alexithymia Scale (TAS) and the Internal Powerful others and Chance Scale. The unipolar major depressives were divided into two subgroups using the endogenomorphic subscale of the Hamilton Depression Rating Scale. There are respectively 25 and 17 depressives in the nonendogenomorphic (NENDO) and endogenomorphic (ENDO) subgroups. The unipolar major depressives were significantly more anhedonic, alexithymic and externalized than the controls. In the ENDO group the PAS and TAS Feelings scores were positively correlated suggesting that a third variable of emotional deficit could characterize endogenomorphic depression. In the NENDO group the PAS, TAS Daydreaming, Powerful others and Chance scores were positively correlated. In nonendogenomorphic depression anhedonia could be related to a poverty of imagery and could be interpreted as a consequence of external causes.

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

The objective of this study was to provide a reliable instrument to measure morningness for upcoming studies in French samples, using the Composite Scale of Morningness (CSM), which has been translated into French. Nursing students (n = 356) completed the questionnaire between February and March 1997. The total score obtained was independent of age and gender, and normally distributed. The reliability was high (Cronbachs alpha = 0.85), and factorial analysis confirmed the unidimensionality of the scale. Evening-type subjects are thought to score under 31, and morning-type subjects are thought to score above 44. As an external validation, morningness was associated, on weekdays and weekends, with early rising times and bedtimes and early peak times of physical and mental performance. In conclusion, we found that the English and the French versions of the Composite Scale of Morningness gave identical results. The scale is reliable and can be used for French-speaking adult samples. Nevertheless, normative data and other external validity criteria are needed.

Anhedonia in the deficit syndrome of schizophrenia.

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.