Social cognition in schizophrenia: Validation of an ecological fMRI task.

Neuroimaging studies have revealed brain regions involved in social cognition, which reportedly show functional alterations in schizophrenia. However, the social neural network has not been investigated with regards to language perception and social interactions in daily life. Here we developed and validated an integrative fMRI task to explore the neural basis of social cognition with regards to language perception in schizophrenia. The task comprised listening to film extracts and inferring mental states to characters. We first identified the functional network activated during the task in 28 healthy controls (HC). Next, we evaluated the reproducibility of Blood-Oxygen-Level Dependent (BOLD) variations in 14 HC participants. Finally, we investigated network impairment in 20 patients with schizophrenia (SZ) compared to HC. The HC group exhibited bilateral activation in the superior and middle temporal gyri (including the poles and the temporo-parietal junction). Overall, our novel integrative task induced activation of a functional network with good reproducibility and involved in language conveying social information. Compared to the HC group, the SZ group showed decreased recruitment of the right temporo-parietal junction. These findings may be useful for testing the impact of remediation on the brain, particularly on the network of language conveying social information.

[Cost-effectiveness analysis of aripiprazole once-monthly versus paliperidone palmitate once-monthly in the treatment of schizophrenia in France]. / Analyse coût-efficacité de l'aripiprazole injectable à libération prolongée (AILP) comparé au palmitate de palipéridone (PP) dans le traitement de la schizophrénie en France.

OBJECTIVE: The aim of the study was to estimate the cost-effectiveness ratio of aripiprazole once-monthly compared to once-monthly injectable paliperidone palmitate in the treatment of schizophrenia in France on the basis of results and data from the QUALIFY study. METHODS: Consumed resources data measured with a dedicated questionnaire and results on the quality of life scales from the QUALIFY study were combined with French standard unit costs of each collected consumed resources during QUALIFY to estimate the cost-effectiveness ratios of the two products. Multivariate sensitivity analyses were performed to test the combined impact of the different assumptions. RESULTS: Findings of the study showed greater efficacy on the quality of life (QLS) and psychiatric evaluation scales (CGI-S and CGI-I) observed in QUALIFY of aripiprazole compared with paliperidone palmitate. Findings also suggest a trend (P=0.0733) in the reduction of total costs linked to a statistical decrease (P<0,0001) in drug costs in the aripiprazole group. These findings are reinforced by the probabilistic sensitivity analyses. CONCLUSION: Aripiprazole appeared to be more cost-effective than paliperidone palmitate in the French context. Limits of this study are mainly related with the duration of the clinical trial and to assumptions on the transposability of measured consumed resources in the international clinical trial to the French healthcare system.

[Pseudo-pheochromocytoma due to iproniazid: A case report]. / Pseudo-phéochromocytome médicamenteux sous iproniazide : à propos d'un cas.

INTRODUCTION: Pheochromocytoma is suggested by the presence of severe and paroxysmal hypertension associated with hyperadrenergy clinical signs. If the diagnosis of pheochromocytoma is ruled out, a pseudo-pheochromocytoma should be considered. We report a clinical observation of pseudo-pheochromocytoma due to iproniazid, a non-selective irreversible monoamine oxidase (MAO) A and B inhibitor in a patient with bipolar disorder. CASE REPORT: A 78-year-old Caucasian male patient treated by iproniazid was hospitalized for depressive relapse. After several episodes of syncopes related to orthostatic hypotension, the patient presented hypertensive crisis. Urinary normetanephrines were increased to twice the upper limit of the normal range. Iproniazid was discontinued. Patient hemodynamic was rapidly stabilized and sympathetic hypertonia diminished. The urinary measurements normalized within two months. The abdominal imaging eliminated an adrenal tumor. CONCLUSION: Iproniazid could be responsible for severe irregular blood pressure associated with abnormal catecholamine metabolism (i.e. pseudo-pheochromocytoma).

[The quality of life in schizophrenia]. / La qualité de vie en schizophrénie.

The World Health Organization defines quality of life as individuals' perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards, and concerns. Quality of life (QoL) is a concept, which reflects multiple as well subjective as objective dimensions. In patients with schizophrenia, quality of life has been negatively correlated with depressive and anxiety symptoms (results seem more unconvincing concerning positive symptoms and cognitive deficits); the remission of positive and negative symptoms has been associated with a better quality of life, but the persistence of depressive symptoms decreases quality of life even when patients were or not in remission; second generation antipsychotics significantly increase more quality of life than first generation antipsychotics; and psychotherapies (rehabilitation, case management...) improve quality of life. Several general and disease-specific QoL scales have been developed and successfully tested in patients with schizophrenia. The most appropriate disease-specific scale is the Quality of Life Scale (Heinrichs et al., 1984) since it takes patients' cognitive deficits into account and because it allows to subtly measuring the patients' subjective feeling during a hetero-evaluation. The Quality of Life Scale is a 21-item scale based on a semi-structured interview, which is comprised of four subscales: interpersonal relations, instrumental role functioning, intra-psychic foundations, and use of common objects and activities. It has been designed initially to assess deficit symptoms in schizophrenia. It is a simple and quite short tool, which is intended for the use as an outcome criterion, a measure of change and an indicator of the efficacy of therapeutic interventions. Convincing metrological qualities have been described: content, construct and nomological validities; inter-raters and test-retest fidelities; it is sensitive to change and to treatments and negatively correlated with symptoms (PANSS) and with clinical state (CGI). Two of the recent major antipsychotic efficacy trials, CATIE and CUtLASS, both adopted the Quality of Life Scale as a measure of quality of life.

[Management of bipolar 1 disorder in children and adolescents]. / Prise en charge du trouble bipolaire de type 1 chez l'enfant et l'adolescent.

Lifetime prevalence of child and adolescent bipolar 1 disorder (BD1) is nearly 0.1 %. Even though it is not a frequent disorder in young people, there is an increased interest for this disorder at this age, because of the poor outcome, the severe functional impairments and the major risk of suicide. Diagnosis is complex in view of the more frequent comorbidities, the variability with an age-dependant clinical presentation, and the overlap in symptom presentation with other psychiatric disorders (e.g. disruptive disorders in prepubertal the child and schizophrenia in the adolescent). The presentation in adolescents is very similar to that in adults and in prepubertal children chronic persistent irritability and rapid mood oscillation are often at the foreground. For a while, such presentations were considered as BD-not otherwise specified (BD-NOS), which can explain the outburst of the prevalence of bipolar disorder in children in the US. Longitudinal studies that look for the outcome of such emotional dysregulations have not revealed an affiliation with bipolar disorder spectrum, but with depressive disorders in adulthood. The diagnosis of Disruptive Mood Dysregulation Disorder was proposed in the DSM-5 to identify these children and to prevent confusion with bipolar disorder. The goals of the pharmacological and psychosocial treatments are to control or ameliorate the symptoms, to avoid new episodes or recurrences, to improve psychosocial functioning and well-being, and to prevent suicide. In the US, lithium and four atypical antipsychotics have been approved by the FDA for 10 to 13-year-olds (risperidone, olanzapine, aripiprazole and quetiapine). In France, only lithium salts (after the age of 16) and aripiprazole (after the age of 13) are recommended. Psychosocial treatments, such as a familial or individual approach are developing.

[Cognitive behavior therapy after first-episodes psychosis]. / Thérapies cognitives et comportementales après les premiers épisodes psychotiques.

Cognitive behavior therapy (CBT) is recommended for the treatment of first-episode psychosis (FEP) patients. It can be offered in acute state or during the remission of the episode. Up to date, effects of CBT have been examined in several controlled and randomized trials in FEP. Combined with antipsychotic medications, results have demonstrated that CBT decreases positive psychotic symptoms, enhances quality of live, self-esteem and insight, and diminishes the intensity of comorbide symptoms, such as trauma or suicide behavior. CBT might be particularly efficient in individuals wishing to reintegrate premorbide functioning and those with low duration of untreated psychosis. Despite these encouraging results, psychosis orientated CBT are underused in France. The validation of group CBT specifically designed for FEP should enhance the range of patients receiving this treatment. Moreover, early CBT interventions for people at ultra high-risk for psychosis and assertive community treatments should be developed.

[Cognitive deficits in first episode psychosis patients and people at risk for psychosis: from diagnosis to treatment]. / Troubles cognitifs des sujets présentant un premier épisode psychotique et à haut risque de transition vers la psychose: du repérage à la prise en charge.

BACKGROUND: Up to now, studies have not demonstrated significant efficacy of antipsychotics on cognitive impairments in patients with psychotic disorders. These cognitive deficits are of particular interest since they traditionally start early before the diagnosis of psychosis. They are observed during premorbid and prodromal stages, and during the first episode of psychosis. Moreover, cognitive impairments may be detected without any psychotic symptoms (such as positive symptoms) suggesting their development independently of the psychotic symptoms. Cognitive disturbances consist of impairments of episodic and working memories, intellectual functioning, executive functions (planning, inhibition, and cognitive flexibility), selective and sustained attentions and social cognition (emotion, recognition, theory of mind). The altered cognitive functions observed in schizophrenia are the same as in earlier stages but at a lower level of severity. LITERATURE FINDINGS: Data suggest that cognitive deficits can be considered as vulnerability markers of psychosis since they have been described in healthy relatives of psychotic patients with high genetic risk. Cognitive deficits might also be considered as predictive of the occurrence of the disease after the first episode of psychosis. Indeed, retrospective studies suggest cognitive impairments in patients with schizophrenia during premorbid and prodromal phases but not in bipolar patients. Cognitive assessment might be of particular interest in people at risk for psychosis, in order to differentiate diagnostic outcomes. Cognitive functioning impairs until the diagnosis of first episode psychosis, even though cognitive profiles are quite heterogeneous in these patients. Once the diagnosis of schizophrenia is considered, cognitive deficits may be stable, although the literature is still controversial. Several factors such as symptoms and gender can contribute in diversifying the cognitive profiles. Moreover, age of onset might worsen the prognosis because of a disruption of the cognitive development and the disturbance of scholarship in young individuals. DISCUSSION: Considering these results, the treatment of cognitive deficits should be initiated as soon as possible, e.g. in people at risk for psychosis in order to reinforce the normal cognitive development, prevent cognitive decline and to preserve the educational, professional and social status. Since antipsychotic medications do not impact on cognitive functioning, alternative therapeutics should be developed such as cognitive remediation. Several studies and meta-analyses have shown that cognitive remediation programs are particularly efficient in patients with schizophrenia or bipolar disorders. Contrary to antipsychotics, these techniques should be used in patients with a first psychotic episode, but also in individuals with subpsychotic symptoms, subthreshold to the diagnosis of schizophrenia.

[Schizophrenia and semantic priming effects]. / Schizophrénie et effets d'amorçage sémantique.

INTRODUCTION: This article is a review of studies using the semantic priming paradigm to assess the functioning of semantic memory in schizophrenic patients. CONTEXT: Semantic priming describes the phenomenon of increasing the speed with which a string of letters (the target) is recognized as a word (lexical decision task) by presenting to the subject a semantically related word (the prime) prior to the appearance of the target word. This semantic priming is linked to both automatic and controlled processes depending on experimental conditions (stimulus onset asynchrony (SOA), percentage of related words and explicit memory instructions). Automatic process observed with short SOA, low related word percentage and instructions asking only to process the target, could be linked to the "automatic spreading activation" through the semantic network. Controlled processes involve "semantic matching" (the number of related and unrelated pairs influences the subjects decision) and "expectancy" (the prime leads the subject to generate an expectancy set of potential target to the prime). These processes can be observed whatever the SOA for the former and with long SOA for the later, but both with only high related word percentage and explicit memory instructions. LITERATURE FINDINGS: Studies evaluating semantic priming effects in schizophrenia show conflicting results: schizophrenic patients can present hyperpriming (semantic priming effect is larger in patients than in controls), hypopriming (semantic priming effect is lower in patients than in controls) or equal semantic priming effects compared to control subjects. DISCUSSION: These results could be associated to a global impairment of controlled processes in schizophrenia, essentially to a dysfunction of semantic matching process. On the other hand, efficiency of semantic automatic spreading activation process is controversial. These discrepancies could be linked to the different experimental conditions used (duration of SOA, proportion of related pairs and instructions), which influence on the degree of involvement of controlled processes and therefore prevent to really assess its functioning. In addition, manipulations of the relation between prime and target (semantic distance, type of semantic relation and strength of semantic relation) seem to influence reaction times. However, the relation between prime and target (mediated priming) frequently used could not be the most relevant relation to understand the way of spreading of activation in semantic network in patients with schizophrenia. Finally, patients with formal thought disorders present particularly high priming effects relative to controls. CONCLUSION: These abnormal semantic priming effects could reflect a dysfunction of automatic spreading activation process and consequently an exaggerated diffusion of activation in the semantic network. In the future, the inclusion of different groups schizophrenic subjects could allow us to determine whether semantic memory disorders are pathognomonic or specific of a particular group of patients with schizophrenia.