Search

Antidepressants effectiveness in major depressive disorder (MDD) is still questioned because the extrapolation of randomized controlled trial (RCT) results to "real life" settings is problematic. The application of the RCT paradigm in a disorder of this type, where global care plays a central role, raises questions regarding the internal and external validity of this type of study. Outcome measurement, attrition rates, the ability of the double-blind design to control for expectations, placebo response, the representativeness of trial participants and publication bias are major methodological pitfalls. This review discusses these issues. It is illustrated using original data and proposes some alternatives for assessing antidepressant effectiveness via different approaches. Some are easy to implement, such as ecological measures, qualitative approaches, improvement of analytical strategy and improvement of blinding procedures. Some are sophisticated, involving temporary deception to deal with the confounding effect of expectations, and they raise ethical issues. Others resort to external validity, this being the case in observational studies. But all are necessary to explore antidepressant effectiveness., (Copyright © 2013 John Wiley & Sons, Ltd.)

Bipolar disorder is a chronic mental illness associated with high levels of somatic morbidity, comorbidity and mortality. Treatment guidelines for bipolar mania generally recommend initiating first-line therapy with a second-generation antipsychotic or mood stabiliser, either alone or in combination. Asenapine is a second-generation antipsychotic with a unique receptor binding profile, licensed for the treatment of manic episodes in adults with bipolar I disorder. 'Real-world' data are needed to complement evidence from clinical trials, in order to provide clinicians with pragmatic information regarding the likely risks and benefits of using a new agent in clinical practice. Evidence from real-world case reports demonstrates that - as in clinical trials - asenapine is effective in treating mania and mixed episodes associated with bipolar I disorder, whether used as monotherapy or in combination with a mood stabiliser. It has a rapid onset of antimanic effect and an early improvement is associated with treatment outcome. Asenapine also shows promise in controlling depressive symptoms and clinically challenging mixed states. Asenapine has a favourable tolerability profile, compared with other first-line agents, having a minimal impact on weight and metabolic parameters. Asenapine should be considered a first-line treatment option for adults with bipolar I disorder.

Background: Deep brain stimulation has shed new light on the central role of the prefrontal cortex (PFC) in obsessive compulsive disorder (OCD). We explored this structure from a functional perspective, synchronizing neuroimaging and cognitive measures., Methods and Findings: This case-control cross-sectional study compared 15 OCD patients without comorbidities and not currently on serotonin reuptake inhibitors or cognitive behavioural therapy with 15 healthy controls (matched for age, sex and education level) on resting-state (18)FDG-PET scans and a neuropsychological battery assessing executive functions. We looked for correlations between metabolic modifications and impaired neuropsychological scores. Modifications in glucose metabolism were found in frontal regions (orbitofrontal cortex and dorsolateral cortices), the cingulate gyrus, insula and parietal gyrus. Neuropsychological differences between patients and controls, which were subtle, were correlated with the metabolism of the prefrontal, parietal, and temporal cortices., Conclusion: As expected, we confirmed previous reports of a PFC dysfunction in OCD patients, and established a correlation with cognitive deficits. Other regions outside the prefrontal cortex, including the dorsoparietal cortex and the insula, also appeared to be implicated in the pathophysiology of OCD, providing fresh insights on the complexity of OCD syndromes.

Objective: We sought to identify apathy metabolic bases in Parkinson disease (PD)., Methods: A total of 45 patients with PD who were not clinically depressed (Montgomery-Åsberg Depression Rating Scale [MADRS] <21) and had no dementia (Mattis Dementia Rating Scale [MDRS] >130) were assessed with the Apathy Evaluation Scale (AES) and underwent a resting-state F-18 fluorodeoxyglucose PET (FDG-PET) scan. A motor assessment comprising the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) was conducted and total levodopa equivalent daily dose (LEDD) was calculated. Imaging data were analyzed with statistical parametric mapping. Age, LEDD, and MDRS scores were introduced as covariates., Results: Positive correlations were observed between the AES score and cerebral metabolism in the right inferior frontal gyrus (Brodmann area [BA] 47), right middle frontal gyrus (BA 10), right cuneus (BA 18), and right anterior insula (BA 13). Negative correlations were observed between the AES score and cerebellar metabolism in the semilunar lobules bilaterally, within the posterior lobe. Using an AES score equal to or above 42 to define clinical apathy, prevalence in our patient group was 17.8%. The AES score was negatively correlated with the MDRS score and positively correlated with the "retardation" subscore of the MADRS. It was not correlated with either UPDRS III or LEDD., Conclusions: Results indicate that the frontal, temporal, and cerebellar areas known to be involved in reward, emotion, and cognition are also implicated in apathy in patients with PD without dementia or depression. Their roles in the etiopathology of apathy are discussed.

Deep brain stimulation was first developed for movement disorders but is now being offered as a therapeutic alternative in severe psychiatric disorders after the failure of conventional therapies. One of such pathologies is obsessive-compulsive disorder. This disorder which associates intrusive thoughts (obsessions) and repetitive irrepressible rituals (compulsions) is characterized by a dysfunction of a cortico-subcortical loop. After having reviewed the pathophysiological evidence to show why deep brain stimulation was an interesting path to take for severe and resistant cases of obsessive-compulsive disorder, we will present the results of the different clinical trials. Finally, we will provide possible mechanisms for the effects of deep brain stimulation in this pathology., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

An accurate treatment of first episodes in schizophrenia and bipolar disorders has a significant impact on compliance and prognosis. However, existing therapeutic guidelines may be poorly respected and may concern only typical clinical situations. Medical attitudes in clinical practice have been collected and structured on the basis of small interactive meetings (Focus Group [FG]), and a synthesis of practical attitudes has been compared with updated guidelines. The FG method applied to treatment initiation in schizophrenia and bipolar disorder is seen as complementary to evidence-based guidelines. It reveals that, in a reflexive manner, clinical attitudes are often more diverse and frequently consider first treatments after global evaluation, taking more into account external factors such as clinicians' experience, patient's history and willingness, clinical setting, and environment. A symptomatic approach is sometimes preferred, and a better alliance is always considered as a main objective. The FG method could be a supplementary support to continuous medical education., (Copyright © 2012 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Unlabelled: Despite the advantages of antipsychotic treatments via the injectable route of administration, there are still reservations regarding this type of therapy, notably among health professionals. A survey conducted with patients suffering from schizophrenic disorders revealed the positive opinion that they had of their treatment. Another survey showed that nearly half of the patients preferred an injectable form, and two thirds felt they were cared for better, because of the injectable treatment. The slow release form of risperidone allows a choice between two injection sites: the deltoid muscle or the gluteal muscle. A recent study showed the satisfaction of the health professionals towards this novel form. The survey presented here was aimed at collecting the opinion of patients regarding the possibility of choosing the injection site, and the changes it would make., Objectives and Methods: The survey was carried out by the BVA Institute during the first half of 2011. The interviews with the schizophrenic patients, followed-up as out patients and treated with long lasting antipsychotics (n=281), were conducted face to face at the hospital by BVA interviewers specialised in the field of health, without the presence of any health professionals. A total of 32 centres participated in the survey; 38% of the interviews took place in the Paris area and 62% in various regions., Results: Different dimensions were analysed. (1) The perception of injectable treatment was largely positive: among all the patients, 75% claimed they currently felt better once they had started the injectable treatment. (2) The choice of the injection site appeared important to a majority of patients (70% of the total sample; 79% of patients had experienced both sites of injection), 56% claimed that it was legitimate that they be given the choice and they felt that they were thus able to participate in their treatment (58%), their treatment was more acceptable (54%), and they found that their relationship with the doctor or nurse was enhanced (53%). (3) The preference regarding the injection site went to the deltoid muscle, among those who had experienced both sites. (4) The perception of the injection sites confirms this preference, the positive qualifications often being associated with the deltoid site, and the negative qualifications with the gluteal site., Conclusion: The survey presented here could contribute in convincing the health professionals to propose the choice to patients between the two injection sites in order to improve their compliance to treatment. Patients would therefore play a role in the choice of their treatment and hence become more involved in the follow-up., (Copyright © 2012. Published by Elsevier Masson SAS.)

Background: The primary objective of this prospective observational study was to evaluate changes in self-reported disability in patients with anxiety or mood disorders 3 months after initiating antidepressant treatment., Methods: This study included 8396 patients consulting 2433 general practitioners in France for a major mood episode, generalized anxiety disorder, social anxiety disorder, panic disorder, or obsessive-compulsive disorder. Treatment was initiated with the antidepressant that the physician considered appropriate. Patients were evaluated with the Sheehan Disability Scale (SDS), Hospital Anxiety and Depression Scale, and Clinical Global Impression-Severity (CGI-S) at baseline and after 6 and 12 weeks., Results: At 12 weeks, 6617 patients (78.8%) were evaluable. At inclusion, the mean SDS subscores were 6.5 ± 2.2 on the work/school activities dimension, 6.8 ± 1.9 on the social activities dimension, and 6.5 ± 2.0 on the family life dimension. At the 12-week follow-up visit, the mean change in score on these three dimensions was -3.9 ± 2.6, -4.2 ± 2.5, and -4.0 ± 2.5, respectively. At the 12-week follow-up visit, 90.0% of patients were responders (defined as patients whose SDS dimension scores decreased by at least one point) on the work/school SDS subscores; 92.8% were responders on the social life SDS subscores, and 91.1% were responders on family life/home responsibilities SDS subscores. Functional remission (defined as an SDS subscore of 0 at study end) rates were 18.0% for the work/school dimension, 16.8% for the social activities dimension, and 19.5% for the family life dimension. Using a cutoff of ≤2, remission rates were 56.8%, 55.0%, and 58.0%, respectively. Improvements in self-rated disability were correlated with improvements in symptoms measured with clinician-rated CGI-S., Conclusion: Patients consulting for anxiety or mood disorders report significant disability, which can be effectively reduced by antidepressant treatment.

Compelling evidence suggests that both schizophrenia and obsessive compulsive disorder (OCD) are related to deviant neurodevelopment. Neurological soft signs (NSS) have been proposed to be a marker of abnormal brain development in schizophrenia. The purpose of this study is to examine whether NSS are also a marker in patients with OCD, in particular, in early-onset OCD. The authors included 162 subjects and compared patients with OCD, patients with schizophrenia (SCZ), and healthy control subjects. They were all examined for NSS (Krebs' Scale), extrapyramidal symptoms (Simpson-Angus Scale), and were rated on the Abnormal Involuntary Movements Scale (AIMS). The authors found no differences between NSS total scores and subscores in OCD versus controls, whereas total NSS, motor coordination, and motor integration were significantly lower in OCD than in SCZ. OCD patients with early-onset (before age 13) did not differ from those with later-onset OCD. These results support the idea that NSS, as determined by current scales, is relatively specific to schizophrenia, although they do not preclude the existence of a neurological dysfunction in OCD. Further studies are required to determine the type of neurological signs that could be useful trait-markers in the phenotypic characterization of subtype OCD.

Purpose: Only a few European countries have carried out large, community-based, national surveys about psychiatric morbidity. Here is presented the first national French survey, aiming to estimate the prevalence of anxiety disorders and associated comorbidities according to sociodemographic characteristics., Materials and Methods: The Mental Health in General Population (MHGP) database is derived from a representative national survey of the French adult population (n=36,105), conducted between 1999 and 2003. Data collection was done using an anonymous face-to-face interview. The presence of anxiety disorders (generalized anxiety disorder, panic disorder, agoraphobia, social phobia and post-traumatic stress disorder) was assessed using the Mini International Neuropsychiatric Interview., Results: The overall prevalence of anxiety disorders was estimated to be 21.6%, generalized anxiety disorder being the most prevalent one (12.8%). Women, young people, and people earning low income were identified as the more at risk. Major depressive episode, alcohol abuse and drug addiction frequently co-occur with anxiety disorders (28.3, 4.4 and 2.8% respectively)., Conclusion: The MHGP study showed that anxiety disorders are highly prevalent in France with a high frequency of comorbidities. Our results highlight the need for considering anxiety disorders as a public health priority in France as well as in other European countries., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Three common missense variants of the Disrupted in Schizophrenia 1 (DISC1) gene, rs3738401 (Q264R), rs6675281 (L607F) and rs821616 (S704C), have been variably associated with the risk of schizophrenia. In a case-control study, we examine whether these gene variants are associated with schizophrenia and ultra-resistant schizophrenia (URS) in a population of French Caucasian patients. The URS phenotype is characterized according to stringent criteria as patients who experience no clinical, social and/or occupational remission in spite of treatment with clozapine and at least two periods of treatment with distinct conventional or atypical antipsychotic drugs. We find a significant association between DISC1 missense variants and URS. The association with rs3738401 remains significant after appropriate correction for multiple testing. These results suggest that the DISC1 rs3738401 missense variant is statistically linked with ultra-resistance to antipsychotic treatment.

Objective: Dysfunctions of saccadic and/or smooth pursuit eye movements have been proposed as markers of obsessive compulsive disorder (OCD), but experimental results are inconsistent. The aim of this paper was to review the literature on eye movement dysfunctions in OCD to assess whether or not saccades or smooth pursuit may be used to diagnose and characterize OCD., Method: Literature was searched using PubMed, ISI Web of Knowledge, and PsycINFO databases for all studies reporting eye movements in adult patients suffering from OCD., Results: Thirty-three articles were found. As expected, eye movements of the patients with OCD were mostly assessed with simple oculomotor paradigms involving saccadic and/or smooth pursuit control. In contrast to patients with schizophrenia, however, patients with OCD only displayed rather unspecific deficits, namely slight smooth pursuit impairments and longer response latencies on antisaccade tasks. There was no relationship between these deficits and the severity of patients' symptoms. Interestingly, eye movements of the patients with OCD were almost never recorded during more complex cognitive tasks., Conclusion: As in schizophrenia and autism, eye movement recordings during more complex tasks might help to better characterize the cognitive deficits associated with OCD. Such recordings may reveal specific OCD-related deficits that could be used as reliable diagnostic and/or classification tools., (© 2011 John Wiley & Sons A/S.)

Schizophrenia is a severe psychiatric disorder that profoundly affects cognitive, behavioral and emotional processes. The wide spectrum of symptoms and clinical variability in schizophrenia suggest a complex genetic etiology, which is consistent with the numerous loci thus far identified by linkage, copy number variation and association studies. Although schizophrenia heritability may be as high as ∼80%, the genes responsible for much of this heritability remain to be identified. Here we sequenced the exomes of 14 schizophrenia probands and their parents. We identified 15 de novo mutations (DNMs) in eight probands, which is significantly more than expected considering the previously reported DNM rate. In addition, 4 of the 15 identified DNMs are nonsense mutations, which is more than what is expected by chance. Our study supports the notion that DNMs may account for some of the heritability reported for schizophrenia while providing a list of genes possibly involved in disease pathogenesis.

Objective: Major depressive disorder (MDD) is associated with abnormalities in the recognition of emotional stimuli. MDD patients ascribe more negative emotion but also less positive emotion to facial expressions, suggesting blunted responsiveness to positive emotional stimuli. To ascertain whether these emotional biases are modality-specific, we examined the effects of MDD on the recognition of emotions from voices using a paradigm designed to capture subtle effects of biases., Methods: Twenty-one MDD patients and 21 healthy controls (HC) underwent clinical and neuropsychological assessments, followed by a paradigm featuring pseudowords spoken by actors in five types of emotional prosody, rated on continuous scales., Results: Overall, MDD patients performed more poorly than HC, displaying significantly impaired recognition of fear, happiness and sadness. Compared with HC, they rated fear significantly more highly when listening to anger stimuli. They also displayed a bias toward surprise, rating it far higher when they heard sad or fearful utterances. Furthermore, for happiness stimuli, MDD patients gave higher ratings for negative emotions (fear and sadness). A multiple regression model on recognition of emotional prosody in MDD patients showed that the best fit was achieved using the executive functioning (categorical fluency, number of errors in the MCST, and TMT B-A) and the total score of the Montgomery-Asberg Depression Rating Scale., Conclusions: Impaired recognition of emotions would appear not to be specific to the visual modality but to be present also when emotions are expressed vocally, this impairment being related to depression severity and dysexecutive syndrome. MDD seems to skew the recognition of emotional prosody toward negative emotional stimuli and the blunting of positive emotion appears not to be restricted to the visual modality., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Transcranial magnetic stimulation (TMS) is a non-invasive technique used in the treatment of major depression. Meta-analyses have shown that it is more efficient than a placebo and that its efficacy is enhanced by the optimum tuning of stimulation parameters. However, the stimulation target, the dorsolateral prefrontal cortex (DLPFC), is still located using an inaccurate method. In this study, a neuronavigation system was used to perform a comprehensive quantification of target localization errors. We identified and quantified 3 sources of error in the standard method: cap repositioning, interexpert variability in coil positioning and distance between the stimulated point and the expected target. For cap repositioning, the standard deviation was lower than 5mm in the 3 axes. For interexpert variability in coil positioning, the spatial dispersion of the points was higher than 10mm in 2 of the 3 axes. For interindividual anatomical variability, the distance between the actual "reference" DLPFC and its standard determination was greater than 20mm for 54% of the subjects, while one subject out of eleven was correctly targeted which means 10mm or less from the reference. Results showed that interindividual anatomical variability and interexpert variability were the two main sources of error using the standard method. Results demonstrate that a neuronavigation system is mandatory to conduct reproducible and reliable studies., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Aims: Neuronal uncoupling proteins are involved in the regulation of reactive oxygen species production and intracellular calcium homeostasis, and thus, play a neuroprotective role. In order to explore the potential consequences of neuronal uncoupling proteins variants we examined their association in a sample of Caucasian patients suffering from schizophrenia and phenotyped them according to antipsychotic response., Materials & Methods: Using a case-control design, we compared the frequencies of 15 genetic variants spanning UCP2, UCP4 and UCP5 in 106 French Caucasian patients suffering from schizophrenia and 127 healthy controls. In addition, patients with schizophrenia who responded to antipsychotic treatment were compared with patients with ultra-resistant schizophrenia (URS). This latter population presented no clinical, social and/or occupational remission despite at least two periods of treatment with conventional or atypical antipsychotic drugs and also with clozapine., Results: There were no differences in the distribution of the respective alleles between URS and responding patients. However, one haplotype spanning UCP4 was found to be significantly under-represented in URS patients. This relationship remained significant after multiple testing corrections., Conclusion: Although our sample is of limited size and not representative of schizophrenia as a whole, the association found between the URS group and the UCP4 haplotype is noteworthy as it may influence treatment outcome in schizophrenia.

Background: High-frequency bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) is a promising treatment in refractory obsessive-compulsive disorder (OCD)., Method: Using the crossover, randomized, and double-blind procedure adopted by the STOC study, 10 patients treated with high-frequency bilateral STN DBS underwent am 18-fluorodeoxyglucose positron emission tomography (PET) investigation to highlight the neural substratum of this therapeutic approach., Results: The median Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores for all 10 patients were 31 (minimum = 18, maximum = 36) with "Off-Stimulation" status and 19 (minimum = 0, maximum = 30) with "On-Stimulation" status (p = .05). The OCD patients in Off-Stimulation status showed a hypermetabolism in the right frontal middle and superior gyri, right parietal lobe, postcentral gyrus, and bilateral putamen compared with healthy control subjects. A significant decrease in cerebral metabolism was observed in the left cingulate gyrus and the left frontal medial gyrus in On-Stimulation conditions compared with Off-Stimulation conditions. In addition, the improvement assessed by Y-BOCS scores during the On-Stimulation conditions was positively correlated with PET signal changes at the boundary of the orbitofrontal cortex and the medial prefrontal cortex, between PET signal changes and the Y-BOCS scores modifications in On-Stimulation status., Conclusion: This study suggests that the therapeutic effect of STN DBS is related to a decrease in prefrontal cortex metabolism., (Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: The Scale to assess Unawareness of Mental Disorder (SUMD) is a semi-structured interview based on a dimensional and quantitative approach of insight. Different forms of insight are assessed: global insight into mental illness, insight into symptoms and insight into symptom aetiology (i.e. attribution). The SUMD divides the recognition of mental disorders into two concepts: awareness of, and attribution for mental disorders. Awareness relates to the subject's ability to recognize that the phenomenon in question is present, whereas attribution refers to explanations as to cause or source of these signs or symptoms. Thus, the scale distinguishes between the recognition of a symptom and its explanation. For example, the scale allows the investigator to distinguish between a patient's ability to recognize visual hallucinations as such (false perceptions), from his/her ability to explain their cause (e.g. due to mental illness or not)., Objective: The aim of this study was to translate the SUMD (version 3.1 revised) and test its convergent validity among 43 French adult inpatients diagnosed with schizophrenia according to DSM-IV-TR criteria., Methods: Awareness of mental disorder was assessed using the SUMD and the Hamilton Rating Scale for Depression (HAMD) insight item (item 17) respectively, as done in the original English validation study. The SUMD was translated into French then back-translated into English. The back-translation was performed by both English and French native speakers who had no prior knowledge of the scale (the back translation was reviewed by one of the SUMD's authors, Dr Amador, for accuracy). The SUMD manual (v.2/14/99) was also translated into French. Concerning the SUMD directions followed in this study, the first three SUMD items, which are called general items: G1 "Awareness of mental disorder", G2 "Awareness of the achieved effects of medication" and G3 "Awareness of the social consequences of mental disorder" were systematically rated. However, symptom items (four through 20) are not always relevant for every patient. Indeed, for each symptom-item on the scale, it must first be ascertained that the patient has exhibited the particular symptom during the period under investigation. Therefore, for every patient, the symptom checklist was completed prior to filling out the scale, in order to determine which symptom-items were relevant. In addition, symptom attribution items are rated only if the subject received a score between 1 and 3 on the awareness item. Two periods of time of insight were assessed: "current" insight involved rating the highest level of awareness obtained at the time of the interview for the psychopathology present at anytime during the past 7 days. "Past" insight was defined as the present level of awareness during the period of time preceding the current period of investigation., Results: The French translation of the SUMD achieved good convergent validity with the insight item of the Hamilton rating scale for depression., Discussion: The SUMD has proven to be a reliable and valid instrument to assess insight into schizophrenia. The more psychometrically sound rating tools we have at our disposal, many of which have been published in non French journals, the more we will be able to sharpen our assessment of insight into schizophrenia. We are facing an epistemic paradox in which quantification helps description, i.e. we need to have access to different rating tools to measure insight in order to improve our knowledge of the causes, course and treatment of poor insight into mental disorders., (Copyright © 2010 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Background: Schizophrenia (SCZ) is one of the most disabling psychiatric disorders. It is thought to be due to a complex interplay between polygenic and various environmental risk factors, although recent reports on genomic copy number variations suggest that a fraction of the cases could result from variably penetrant de novo variants. The gene encoding the synaptic motor protein kinesin 17 (KIF17) involved in glutamatergic synapse is a candidate gene for SCZ., Methods: As part of our Synapse to Disease project, we resequenced KIF17 in a cohort of individuals with sporadic SCZ (188 subjects). Additional populations included autism spectrum disorder (142 subjects), nonsyndromic mental retardation (95 subjects), and control subjects (568 subjects). Functional validation of the human mutation was done in developing zebrafish., Results: Here we report the identification of a de novo nonsense truncating mutation in one patient with SCZ, in kinesin 17, a synaptic motor protein. No de novo or truncating KIF17 mutations were found in the additional samples. We further validated the pathogenic nature of this mutation by knocking down its expression in zebrafish embryos, which resulted in a developmental defect., Conclusions: Together our findings suggest that disruption of KIF17, although rare, could result in a schizophrenia phenotype and emphasize the possible involvement of rare de novo mutations in this disorder., (Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objectives: The present publication sets out to evaluate the position of psychopathology in the 21st century and should also serve as a basis for defining the framework for the future tasks of the WFSBP Task Force., Methods: Review of publications on the various approaches of psychopathology in general and of different tasks, theories and tools of psychopathology approaches in particular., Results: The main tasks of psychopathology are, to record and describe experiential and behavioral abnormalities in their intersubjective context, to explain their origin from an objective scientific perspective, and to attempt to understand them from the subjective perspective of the patient. In order to provide stable fundaments for the work in clinical and scientific psychiatry all three components are indispensable., Conclusions: The future of psychiatry hence lies in the hands of a type of psychopathology that we will call Integrative Psychopathology. The main tasks of psychopathology can only be pursued in close cooperation with other branches of science interested in studying psychiatric issues. Whereas contemporary psychopathology must lay the foundations for that cooperation, Integrative Psychopathology must be complemented by further advancements in Theoretical Psychopathology, so as to enable conceptual new developments, which can then be fruitful for cooperative research and psychiatric clinical practice.

The role of de novo mutations (DNMs) in common diseases remains largely unknown. Nonetheless, the rate of de novo deleterious mutations and the strength of selection against de novo mutations are critical to understanding the genetic architecture of a disease. Discovery of high-impact DNMs requires substantial high-resolution interrogation of partial or complete genomes of families via resequencing. We hypothesized that deleterious DNMs may play a role in cases of autism spectrum disorders (ASD) and schizophrenia (SCZ), two etiologically heterogeneous disorders with significantly reduced reproductive fitness. We present a direct measure of the de novo mutation rate (μ) and selective constraints from DNMs estimated from a deep resequencing data set generated from a large cohort of ASD and SCZ cases (n = 285) and population control individuals (n = 285) with available parental DNA. A survey of ∼430 Mb of DNA from 401 synapse-expressed genes across all cases and 25 Mb of DNA in controls found 28 candidate DNMs, 13 of which were cell line artifacts. Our calculated direct neutral mutation rate (1.36 × 10(-8)) is similar to previous indirect estimates, but we observed a significant excess of potentially deleterious DNMs in ASD and SCZ individuals. Our results emphasize the importance of DNMs as genetic mechanisms in ASD and SCZ and the limitations of using DNA from archived cell lines to identify functional variants., (2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Introduction: The Brief Psychiatric Rating Scale was initially developed as a rapid method to assess symptom change in psychiatric inpatients of various diagnoses. The original version was expanded to an 18-item version and thereafter to a 24-item version to increase sensitivity to a broader range of psychotic and affective symptoms. The latest version of the expanded 24- item BPRS provides probe questions and detailed anchor points for the ratings for each item., Literature Findings: Studies have shown the expanded and anchored 24-item BPRS to be a sensitive and effective measure of psychiatric symptoms with good interrater reliability that can be maintained over time. To our knowledge, there are eight published papers including factor analyses of the BPRS-E(A). While many similarities are evident between these studies, inconsistencies are apparent that may have been due to sample size, characteristics and / or methodological differences in the factor analysis computation. Among these studies, six provided a four-factor solution. There was no French version of this scale available., Methods: After its translation into French and back translation, we investigated the validity of the French BPRS-E(A) version. We carried out a component analysis on the data of 111 participants of various diagnoses, mostly hospitalised for a first psychotic episode, yielding to a three-factor solution (positive symptoms--disorganisation; depression-anxiety and negative symptoms)., Results: A good internal consistency and interrater reliability were found. These results confirm the psychometric value of the BPRS-E(A) in its French version. We compared those findings to earlier reports; similarities and differences are discussed., (Copyright © 2009 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Purpose: Although high-frequency deep brain stimulation of the subthalamic nucleus (STN DBS) improves motor symptoms in advanced Parkinson's disease (PD), clinical studies have reported cognitive, motivational and emotional changes. These results suggest that the STN forms part of a broadly distributed neural network encompassing the associative and limbic circuits. We sought to pinpoint the cortical and subcortical brain areas modulated by STN DBS, in order to assess the STN's functional role and explain neuropsychological modifications following STN DBS in PD., Methods: We studied resting state glucose metabolism in 20 PD patients before and after STN DBS and 13 age-matched healthy controls using (18)F-FDG PET. We used statistical analysis (SPM2) first to compare pre-stimulation metabolism in PD patients with metabolism in healthy controls, then to study metabolic modifications in PD patients following STN DBS., Results: The first analysis revealed no pre-stimulation metabolic abnormalities in associative or limbic circuitry. After STN DBS, metabolic modifications were found in several regions known for their involvement in the limbic and associative circuits., Conclusion: These metabolic results confirm the STN's central role in associative and limbic basal ganglia circuits. They will provide information for working hypotheses for future studies investigating neuropsychological changes and metabolic modifications related to STN DBS, with a view to improving our knowledge of this structure's functional role.

The aim of the present study was to compare patients displaying chronic and treatment-resistant depression with healthy controls, using the resting-state perfusion with arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) technique at 3T. The study focused on the subgenual anterior cingulate cortex (sACC), which is a key component in the pathophysiology of depression. Six patients with chronic and treatment-resistant depression and six healthy control subjects were included. ASL is an innovative imaging technique which sidesteps the limitations of other functional neuroimaging techniques (functional MRI, positron emission tomography). A statistical analysis of perfusion maps was performed using SPM2 software. Statistically significant hyperperfusion regions were found in the depressed patient group compared with the healthy control group in the following: the bilateral sACC, left prefrontal dorsomedian cortex, left ACC and left subcortical areas (putamen, pallidum and amygdala). This study confirmed the involvement of the sACC in depression, particularly chronic and treatment-resistant depression, using ASL at 3T, a safe perfusion technique that seems to be appropriate for investigating functional abnormalities in psychiatric disorders., (Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: There appears to be an overlap between the limbic system, which is modulated by subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD), and the brain network that mediates theory of mind (ToM). Accordingly, the aim of the present study was to investigate the effects of STN DBS on ToM of PD patients and to correlate ToM modifications with changes in glucose metabolism., Methodology/principal Findings: To this end, we conducted (18)FDG-PET scans in 13 PD patients in pre- and post-STN DBS conditions and correlated changes in their glucose metabolism with modified performances on the Eyes test, a visual ToM task requiring them to describe thoughts or feelings conveyed by photographs of the eye region. Postoperative PD performances on this emotion recognition task were significantly worse than either preoperative PD performances or those of healthy controls (HC), whereas there was no significant difference between preoperative PD and HC. Conversely, PD patients in the postoperative condition performed within the normal range on the gender attribution task included in the Eyes test. As far as the metabolic results are concerned, there were correlations between decreased cerebral glucose metabolism and impaired ToM in several cortical areas: the bilateral cingulate gyrus (BA 31), right middle frontal gyrus (BA 8, 9 and 10), left middle frontal gyrus (BA 6), temporal lobe (fusiform gyrus, BA 20), bilateral parietal lobe (right BA 3 and right and left BA 7) and bilateral occipital lobe (BA 19). There were also correlations between increased cerebral glucose metabolism and impaired ToM in the left superior temporal gyrus (BA 22), left inferior frontal gyrus (BA 13 and BA 47) and right inferior frontal gyrus (BA 47). All these structures overlap with the brain network that mediates ToM., Conclusion/significance: These results seem to confirm that STN DBS hinders the ability to infer the mental states of others and modulates a distributed network known to subtend ToM.

Introduced at the end of the 1980s, high-frequency deep brain stimulation has shown its efficacy in several neurological disorders, including Parkinson's disease, dystonia and essential tremor, in which cortico-subcortical circuit dysfunction is strongly implicated. The existence of psychiatric symptoms in patients with these syndromes has led to the use of this technique in psychiatric disorders, and especially in severe refractory obsessive-compulsive disorders, even though the anatomical target is still controversial. Other potential indications include refractory chronic depression.

The authors present their surgical experience with the management of patients with dorsum deformities using a precise technique: the external percutaneous approach. The indications for this technique have still not been set out very clearly in the rhinological textbooks or manuals, and so novices (and not only novices) have difficulty in understanding and applying it. We therefore try to systematise and clarify these indications in brief, together with the technical details, providing a comparison with another technique that is in very widespread use at present: the internal lateral osteotomy. Although the external percutaneous approach is not used very often--in our experience in 30% of cases only--we find the results very satisfactory and we recommend it when it is required by the anatomic conditions.

Impulsivity may be induced by therapeutic interventions (dopamine replacement therapies and sub-thalamic nucleus (STN) stimulation) in patients with Parkinson's disease (PD). The present review has two goals. First, to describe the most frequently encountered facets of cognitive impulsivity and to stress the links between cognitive impulsivity and aspects such as reward-related decision making, risk-taking, and time-processing in healthy population. The most widely used related cognitive impulsivity paradigms are presented. Second, to review the results of studies on cognitive impulsivity in healthy volunteers and in patients with PD, the latter support the applicability and clinical relevance of this construct in PD population. Data show that PD treatments may favor impulsivity via different mechanisms. Suggestions on the roles of dopamine and STN in the pathophysiology of cognitive impulsivity are proposed., ((c) 2009 Movement Disorder Society.)

Electroconvulsivotherapy represents a key indication for severe Major Depressive Episode (MDE). However, an hospitalization with a general anaesthesia allowing a seizure induction followed by an almost systematic post-epileptic delirium justifies the development of other brain electrostimulation techniques. Trans-cranial Magnetic Stimulation (TMS) is a technique which offers to transform an electromagnetic field within the brain in an electric one. This therapeutic has been approved in 2008 in the MDE indication by the Food and Drug Administration. However a better knowledge of brain stimulation parameters such as the number of sequences, intensity, frequency, and the brain target, is necessary. Indeed it could enable to get some more homogeneous clinical results which will drive to the use of this technique in daily practice. Neurosurgical procedures represent also a stake for a better treatment of severe chronic and resistant depression. Whereas Vagus Nerve Stimulation (DBS) failed to be developed in France, Deep Brain Stimulation (DBS) is currently under development in this indication with some promising preliminary results., (Copyright 2009 L'Encéphale. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: Apathy may be induced by subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson disease (PD). We therefore wished to test the hypothesis that apathy induced by STN-DBS correlates with changes in glucose metabolism, using (18)FDG-PET., Methods: Twelve patients with PD were assessed 3 months before (M-3) and 3 months after (M+3) STN-DBS with (18)FDG-PET and the Apathy Evaluation Scale., Results: Apathy had significantly worsened at M+3 after STN-DBS. Positive correlations were observed between this variation in apathy scores and changes in glucose metabolism, especially in the right frontal middle gyrus (Brodmann area [BA] 10) and right inferior frontal gyrus (BA 46 and BA 47). Negative correlations between the two were observed in the right posterior cingulate gyrus (BA 31) and left medial frontal lobe (BA 9)., Conclusion: These preliminary results confirm the role of the subthalamic nucleus in associative and limbic circuitry in humans and suggest that it is a key basal ganglia structure in motivation circuitry.

Alzheimer's disease (AD) is an age-related neurodegenerative disease that affects approximately 24 million people worldwide. A number of different risk factors have been implicated in AD; however, neuritic (amyloid) plaques are considered as one of the defining risk factors and pathological hallmarks of the disease. In the past decade, enormous efforts have been devoted to understand the genetics and molecular pathogenesis leading to neuronal death in AD, which has been transferred into extensive experimental approaches aimed at reversing disease progression. Modern medicine is facing an increasing number of treatments available for vascular and neurodegenerative brain diseases, but no causal or neuroprotective treatment has yet been established. Almost all neurological conditions are characterized by progressive neuronal dysfunction, which, regardless of the pathogenetic mechanism, finally leads to neuronal death. The particular emphasis of this review is on risk factors and mechanisms resulting in neuronal loss in AD and current and prospective opportunities for therapeutic interventions. This review discusses these issues with a view to inspiring the development of new agents that could be useful for the treatment of AD.

An emerging area of research in engineering psychology is the evaluation of text entry for mobile devices using a small number of keys for the control of cursor direction and character selection from a matrix of characters (i.e., selection-based data entry). The present article describes a software tool designed to reduce time and effort in the development of prototypes of alternative selection-based text-entry schemes and their empirical evaluation. The tool, available for distribution to researchers, educators, and students, uses Action Script code compiled into an executable file that has an embedded Adobe Flash Player and is compatible with most operating systems (including Microsoft Windows, Apple OSX, and Linux).

This paper aims at providing a selective review of the major issues and findings concerning suicide in Huntington's disease. Most of the authors found a four times higher suicidal occurrence in Huntington patients than in the general population. No specific individual risk factor was found except the lack of offspring and psychological support. This paper emphasizes the need of appropriate psychiatric cares for Huntington patients in order to prevent, as much as possible, their suicidal behaviors.

Background: Severe, refractory obsessive-compulsive disorder (OCD) is a disabling condition. Stimulation of the subthalamic nucleus, a procedure that is already validated for the treatment of movement disorders, has been proposed as a therapeutic option., Methods: In this 10-month, crossover, double-blind, multicenter study assessing the efficacy and safety of stimulation of the subthalamic nucleus, we randomly assigned eight patients with highly refractory OCD to undergo active stimulation of the subthalamic nucleus followed by sham stimulation and eight to undergo sham stimulation followed by active stimulation. The primary outcome measure was the severity of OCD, as assessed by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), at the end of two 3-month periods. General psychopathologic findings, functioning, and tolerance were assessed with the use of standardized psychiatric scales, the Global Assessment of Functioning (GAF) scale, and neuropsychological tests., Results: After active stimulation of the subthalamic nucleus, the Y-BOCS score (on a scale from 0 to 40, with lower scores indicating less severe symptoms) was significantly lower than the score after sham stimulation (mean [+/-SD], 19+/-8 vs. 28+/-7; P=0.01), and the GAF score (on a scale from 1 to 90, with higher scores indicating higher levels of functioning) was significantly higher (56+/-14 vs. 43+/-8, P=0.005). The ratings of neuropsychological measures, depression, and anxiety were not modified by stimulation. There were 15 serious adverse events overall, including 1 intracerebral hemorrhage and 2 infections; there were also 23 nonserious adverse events., Conclusions: These preliminary findings suggest that stimulation of the subthalamic nucleus may reduce the symptoms of severe forms of OCD but is associated with a substantial risk of serious adverse events. (ClinicalTrials.gov number, NCT00169377.), (2008 Massachusetts Medical Society)

Objective: To test the hypothesis that emotion recognition and apathy share the same functional circuit involving the subthalamic nucleus (STN)., Methods: A consecutive series of 17 patients with advanced Parkinson's disease (PD) was assessed 3 months before (M-3) and 3 months (M+3) after STN deep brain stimulation (DBS). Mean (+/-S.D.) age at surgery was 56.9 (8.7) years. Mean disease duration at surgery was 11.8 (2.6) years. Apathy was measured using the Apathy Evaluation Scale (AES) at both M-3 and M3. Patients were also assessed using a computerised paradigm of facial emotion recognition [Ekman, P., & Friesen, W. V. (1976). Pictures of facial affect. Palo Alto: Consulting Psychologist Press] before and after STN DBS. Prior to this, the Benton Facial Recognition Test was used to check that the ability to perceive faces was intact., Results: Apathy had significantly worsened at M3 (42.5+/-8.9, p=0.006) after STN-DBS, in relation to the preoperative assessment (37.2+/-5.5). There was also a significant reduction in recognition percentages for facial expressions of fear (43.1%+/-22.9 vs. 61.6%+/-21.4, p=0.022) and sadness (52.7%+/-19.1 vs. 67.6%+/-22.8, p=0.031) after STN DBS. However, the postoperative worsening of apathy and emotion recognition impairment were not correlated., Conclusions: Our results confirm that the STN is involved in both the apathy and emotion recognition networks. However, the absence of any correlation between apathy and emotion recognition impairment suggests that the worsening of apathy following surgery could not be explained by a lack of facial emotion recognition and that its behavioural and cognitive components should therefore also be taken into consideration.

Rationale: Within the framework of an evaluation program for the prevention of suicide in Brittany conducted by the academic department of psychiatry (University of Rennes, Brittany, France), we have addressed the issue of the potential usefulness of psychological autopsy as a tool for the better comprehension of suicide risk factors., Method: We reviewed the appropriate literature in 30 articles found amongst those obtained from the "Medline" database. These articles were selected according to the quality of their methodology. For the Medline data retrieval search, the following keywords were used: "psychological autopsy", "psychiatric autopsy", "psychological autopsy and methodology", "psychiatric autopsy and methodology". This review's objective was to determine, firstly the nature and the content of psychological autopsies, secondly to evaluate their use as a methodological tool to assist the comprehension and prevention of suicide. Finally, it was also to assess its feasibility for use in France., Results: The majority of the published studies using psychological autopsy for the evaluation of suicide expertise came from Scandinavian or Anglo-Saxon countries. Schneidman [Schneidman ES. The psychological autopsy. Suicide Life Threat Behav 1981;11:325-40], whose aim was to clarify the causes of sudden death related to psychological circumstances, focused on suicidal intentions and the symptoms exhibited. He coined the term: "psychological autopsy". Gradually, the definition of psychological autopsy has evolved and is now being used for the evaluation of death by suicide with a single goal in mind: to retrospectively identify any suicidal predictive and risk factors available at the time of the event. At present, no unequivocal definition of "psychological autopsy" has been put forth. However, this formerly only descriptive procedure is now becoming more analytical in nature (comparison of psychiatric profiles between pre- and postmortem assessments, research on precipitating factors, comorbidity studies...). Presently, it corresponds to a methodological tool to be used essentially for case reports that vary a great deal and do not permit cross-comparisons with other case-studies. For the past fifteen years, case-control studies in this field have become more frequent with various choices of control groups: healthy subjects with no psychiatric history, as well as attempted suicides, with or without a psychiatric history. Partial standardization of autopsy procedures is now possible with some data extracted from police inquiries, medical charts, or data gathered following interviews with the deceased patient's relatives., Conclusion: In the aggregate, the literature review showed that the aims of psychological autopsy include understanding and prevention of suicide in a population-based sample. It seems difficult to generalize with results from other population references. In France, the use of psychological autopsy as a standardized tool for the assessment of suicidal behaviors would be difficult, due to the complexity of the procedures involved: data coming from external sources, such as medical sources, is nearly impossible to obtain. Practitioners would be required to overcome administrative rules and regulations, plus incurring the high costs of such procedures. They must also take into account ethical considerations that make such interviews with the deceased patient's relatives difficult to obtain. Be this as it may, the French Ministry of Health is presently attempting to find a solution in order to alleviate the all too frequent problem of suicide in the population at large and to promote suicide prevention in France.

Escitalopram has shown some different pharmacologic properties compared to its racemic molecule, citalopram. When comparing with venlafaxine, similar efficacy of this drug was observed, notably when considering the frequency of responders [50% of decrease on the Montgomery and Asberg Depression rating Scale (MADRS)] and the frequency of remitters (MADRS<12), even when the doses of both drugs were increased up to 20 mg per day for escitalopram and 225 mg per day for venlafaxine. In addition, a recent study conducted by Jonas et al. (2006) [Jonas J, Bose A, Alexopoulos G, et al. Double blind comparison of escitalopram and duloxetine in the acute treatment of Major Depressive Disorder 45th Annual Meeting of the American College of Neuropsychopharmacology December 2006] suggested a better efficacy of escitalopram in comparison to duloxetine. When considering severe major depressive episodes, the efficacy of escitalopram compared to noradrenalin and serotonin reuptake inhibitors (NaSRI) could be superior, with a more important rate of remitters in the escitalopram group. Regarding the tolerance of both types of drugs, the percentage of patients who withdrew the drug for side-effects would be higher in patients on venlafaxine. This increase in frequency of side-effects has been observed in different studies conducted with venlafaxine and duloxetine. All these data highlight the advantages of escitalopram in the treatment of major depressive episodes and escitalopram has, therefore, obtained marketing approval in France with some specific mentions in favour of this drug.

Deep brain stimulation (DBS) of the bilateral subthalamic nucleus (STN) in Parkinson's disease is thought to produce adverse events such as emotional disorders, and in a recent study, we found fear recognition to be impaired as a result. These changes have been attributed to disturbance of the STN's limbic territory and would appear to confirm that the negative emotion recognition network passes through the STN. In addition, it is now widely acknowledged that damage to the orbitofrontal cortex (OFC), especially the right side, can result in impaired recognition of facial emotions (RFE). In this context, we hypothesized that this reduced recognition of fear is correlated with modifications in the cerebral glucose metabolism of the right OFC. The objective of the present study was first, to reinforce our previous results by demonstrating reduced fear recognition in our Parkinson's disease patient group following STN DBS and, second, to correlate these emotional performances with glucose metabolism using (18)FDG-PET. The (18)FDG-PET and RFE tasks were both performed by a cohort of 13 Parkinson's disease patients 3 months before and 3 months after surgery for STN DBS. As predicted, we observed a significant reduction in fear recognition following surgery and obtained a positive correlation between these neuropsychological results and changes in glucose metabolism, especially in the right OFC. These results confirm the role of the STN as a key basal ganglia structure in limbic circuits.

Aripiprazole is indicated for the treatment of schizophrenia in Europe and the United States, and for bipolar disorders in the latter. Nevertheless, a review of recent literature has shown that aripiprazole has been studied in many other disorders, notably resistant depression, anxiety, obsessive-compulsive disorder, borderline personality, Tourette syndrome, addiction, psychotic symptoms in children and adolescents, and neurological and psychiatric disorders in the elderly (late onset delusional disorders, Alzheimer, Parkinson, and delirium). The study of aripiprazole in these numerous indications is motivated by its excellent tolerance and original pharmacological effect (partial agonistic effect on the D2 and 5-HT1A receptors, and antagonistic effect on the 5-HT2A receptors). This paper reviews the recent literature, with particular attention paid to the level of proof provided by these various studies.

Introduction: Insight is more than frequently altered in schizophrenia, rupture of treatment being one the most known consequences of this impairment. Two different types of scales can be used to assess consciousness: self-questionnaires directly filled-in by the patient or questionnaires assessed by a psychiatrist after an interview. AIM OF THE STUDIES: The goal of this study was first to assess insight in schizophrenic patients with these two different types of scales and then try to find a link between insight impairment and schizophrenic symptoms. The self-questionnaire was the Marks et al. Self Appraisal of Illness Questionnaire (SAIQ) [Schizophr Res 45 (2000) 203-11], 17 items finally giving four scores (consciousness of illness, consequences of schizophrenia, need for treatment and worrying about illness) plus a total score of insight. The other questionnaire was the Amador Scale for assessment of Unawareness of Mental Disease [Amador XF, Strauss DH. The scale to assess unawareness of mental disorder (SUMD). Columbia University and New-York State Psychiatric Institute;1990], consisting in an interview with a psychiatrist who finally assesses four dimensions (consciousness of illness, symptoms, need for treatment and consequences of illness) plus a total score. In addition to these scores, Amador's scale gives the opportunity to score attribution a patient gives to illness for his symptoms., Patients: Thirty-one patients whose schizophrenia diagnosis had been previously made according to DSM-IV criteria were included. Half were outpatients, half inpatients. Drug prescriptions were controlled; all of the patients being medicated with an antipsychotic, a benzodiazepine and a sleep inducer. They were all assessed by the two scales previously mentioned and the Positive And Negative Syndrome Scale [Kay SR, Opler LA, Fiszbein A. Positive and negative syndrome scale. Traduction de Lepine JL. In: Guelfi JD, éditeur. Evaluation clinique standardisée, tome II. Castres : Editions médicales Pierre Fabre;1996]., Results: Total scores of insight scales were significantly correlated (p<0.001). For each questionnaire, the four different scores were independent from each other (p<0.001). There was no correlation found between insight scales and schizophrenic symptoms intensity., Conclusion: Considering symptom attribution, being unconscious of a symptom and being enable to attribute it to schizophrenia were linked, which could refer to Frith's theory of schizophrenia [Frith CD. Neuropsychologie de la schizophrénie. Psychiatrie ouverte. Paris: PUF;1996 (208p.)] and attribution impairment as a main dysfunction. The two different types of scales seem to be effective. The significant correlation between them suggests they assess the same dimension. This preliminary study will be followed by a validation study of the french translation of the SAIQ.

Among the second generation antipsychotics, aripiprazole presents a new pharmacological profile, basically differentiated by a partial agonist effect on the D2 and D3 dopaminergic receptors. Five short-term efficacy studies, conducted on 1648 patients presenting with schizophrenia or acute relapse of schizoaffective disorders, demonstrated the greater efficacy of aripiprazole than the placebo and comparable efficacy to that of haloperidol and risperidone. The short-term tolerance profile was characterised by a lesser incidence of the extrapyramidal side effects and drowsiness than with haloperidol. Two thousand six hundred and eighty five patients were followed-up over a period of 26 to 52 weeks in five clinical trials versus a placebo and haloperidol, olanzapine, quetiapine and risperiodone: demonstrated efficacy in maintaining the response to treatment and on the delay before relapse was comparable to the other antipsychotics. The classical side effects of antipsychotics decreased in the long-term. Versus olanzapine, a glucid and lipid profile, clearly in favour of aripiprazole, was completed by a lesser incidence of hyperprolactinaemia. Aripiprazole is effective on all the dimensions of schizophrenia: the positive and negative and depressive and anxious symptomatology. It appears to be of interest, notably on the cognitive dimension, which should motivate more in-depth exploration of its place in the treatment in the early stages of schizophrenia. Its therapeutic schedule and the methods of initiation are an essential criterion to the success of treatment, notably during the substitution of other antipsychotics. The clinical and pharmacological originality of aripiprazole would justify the terminology of a "third generation antipsychotic".

Background: Naturalistic effectiveness trials of atypical antipsychotics are needed to provide broader information on efficacy, safety, and tolerability in patients with schizophrenia treated in a community practice setting., Method: In this 26-week, open-label, multicentre study, patients with schizophrenia requiring a switch in antipsychotic medication because current medication was not well tolerated and/or clinical symptoms were not well controlled were randomized to receive aripiprazole or an atypical antipsychotic standard of care (SOC) treatment (i.e., olanzapine, quetiapine, or risperidone based on the investigator's judgment of the optimal treatment for the individual patient and the patient's prior response to antipsychotic medication). The primary objective was to compare the effectiveness of a 26-week treatment of aripiprazole versus SOC, as measured by the Investigator Assessment Questionnaire (IAQ) total score at Week 26 last observation carried forward (LOCF) (primary endpoint), a validated measure that monitors relief or worsening of 10 key symptoms associated with the psychopathology of schizophrenia and side effects of antipsychotic treatment. Secondary objectives were to further assess effectiveness using the Clinical Global Impression - Global Improvement (CGI-I) and Clinical Global Impression - Severity of Illness scale, to assess time to treatment discontinuation, patient preference of medication, quality of life, and the tolerability of aripiprazole compared with SOC., Results: Aripiprazole treatment (n=268) resulted in significantly better effectiveness than SOC treatment (n=254; P<0.001; Week 26 LOCF) as evidenced by the IAQ total score beginning at Week 4 (the first assessment point) and sustained through Week 26. A similar relationship was demonstrated among patients who completed the study (observed cases analysis); aripiprazole was associated with significantly better effectiveness at all time points with a greater differential effect from SOC over time. Patients treated with aripiprazole also demonstrated significantly greater improvements on the CGI-I scale (responder rate, P=0.009 at Week 26 LOCF), as well as on quality of life (Quality of Life scale total score; P<0.001 at Week 26). Furthermore, a significantly higher proportion of patients receiving aripiprazole rated their study medication as "much better" on the Preference of Medication Questionnaire (POM) scale than their pre-study medication compared with SOC patients (P<0.001; Week 26). Time to treatment discontinuation and rates of discontinuation due to adverse events were similar in both treatment groups. The incidence of patients with one or more extrapyramidal symptom (e.g., akathisia, dystonia, parkinsonian events, and residual events) was higher in patients receiving aripiprazole compared with patients treated with SOC (13.5% vs. 5.6%); however, a higher proportion of patients in the SOC-treated group had clinically significant weight gain (21.2% vs. 7.3% for aripiprazole) and potentially clinically relevant elevated fasting levels of total cholesterol, low-density lipoprotein cholesterol, triglycerides, and serum prolactin compared with patients receiving aripiprazole., Conclusions: Aripiprazole is an effective atypical antipsychotic for the treatment of schizophrenia, demonstrating better effectiveness than SOC agents used in this study in patients for whom a switch in antipsychotic medication was warranted.

Introduction: In this study, we present seven case reports concerning patients suffering from schizophrenia or schizo-affective disorders, treated by aripiprazole., Study Design: Through these patient case reports, we have attempted to highlight the specificities of aripiprazole's action on schizophrenic symptoms, especially in the cognitive dimension. In acting as a regulator more than as a brake on the translation messages between neurons, aripiprazole does not increase cognitive disorders, but may have a procognitive affect., Results: We particularly noticed an improvement in attention abilities, both in selective attention - in order to take into account the context of the situation - and in sustained attention allowing patients to maintain a stable and appropriate level of efficiency while performing an activity. Case reports (n 2, n 3 and n 5) also seem to show the ability of aripiprazole to improve working memory: indeed, abilities of patients to maintain and recall information regarding different cognitive activities required in rehabilitation psychiatric care were noticed with aripiprazole while they were not with previous antipsychotic drugs used in the same patients., Discussion: Our sample, although too small for global consideration, suggests that aripiprazole provides stimulating properties for schizophrenic patients including those with primary deficient syndrome. This action, probably through cognitive improvement, needs some clarification in more precisely defining deficit features as juxtaposed by the classical criteria used on the SANS-SAPS and PANSS scales. Finally, we should stress aripiprazole's rapidity of effect. In half the cases, the reported improvement in our patients occurred during the first week of treatment. Hence, the patient should be informed of the short time-span effect for aripiprazole, in order to prevent the emergence of symptoms due to the rapid switch of medication and eventual side effects., Conclusion: Aripiprazole acts as a partial agonist of D2 receptors as well as a partial agonist of 5HT1A and an antagonist of 5HT2A. This drug constitutes the first that permits regulation of both the dopamine and serotonine systems: dopamine activity is blocked when D2 receptors are over-stimulated and increased when D2 receptors require stimulation; on the other hand, in the cortical region, the inactivation of 5HT2A allows for a release of dopamine firing, whereas in the striatum where the 5HT2A receptors density is increased, their blockage inhibits dopamine release and limits extrapyramidal symptoms. In addition, the synergy between 5HT1A antagonism and 5HT2A antagonism seems to provide aripiprazole with both anxiolytic and affective properties. Finally, the absence of an affinity for histamine, muscarinic and adrenergic alpha-1 receptors limits the side effects compared to other antipsychotic drugs.