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Despite international efforts to identify biomarkers of depression, none has been transferred to clinical practice, neither for diagnosis, evolution, nor therapeutic response. This led us to build a French national cohort (through the clinical and research network named SoPsy within the French biological psychiatry society (AFPBN) and sleep society (SFRMS)), to better identify markers of sleep and biological rhythms and validate more homogeneous subgroups of patients, but also to specify the manifestations and pathogeneses of depressive disorders. Before inclusions, we sought to provide a predefined, standardized, and robust set of data to be collected in all centers.

Le présent article propose de faire un retour sur les 10 ans d’expérience du réseau national des 10 centres experts schizophrénie Français, à travers une revue des principales publications scientifiques qui en sont issues.

Alcohol use disorder (AUD) is associated with impaired social cognition, including the disturbance of facial emotion recognition (FER). Previous studies have focused on the assessment of basic emotions decoding among patients with AUD, but the evolution of these performances in the early phase of alcohol withdrawal remains unknown.

10 à 15 % des parturientes développent une dépression du post-partum (DPP). Une physiopathologie propre la distinguerait des autres formes de dépression. La prise en charge médicamenteuse repose sur des traitements non spécifiques. La fluctuation des taux de neurostéroïdes durant la grossesse et après l’accouchement, et leur action sur le récepteur GABA-A sont des mécanismes étudiés.

Accéder à l’emploi et pouvoir s’y maintenir sont non seulement des critères de rétablissement de la schizophrénie mais en constituent aussi un des moyens privilégiés. En dépit du manque de données quantifiées en France concernant l’emploi des personnes vivant avec une schizophrénie, et en particulier les résultats des pratiques visant à réinsérer ces personnes, il est largement reconnu que ce taux d’accès à l’emploi reste faible, certainement inférieur à 20 %, et encore s’agit-il souvent d’insertion en milieu de travail protégé. Les données de recherche internationales dans ce domaine font pourtant apparaître qu’il est possible d’obtenir de bien meilleurs taux d’intégration professionnelle, avec des soutiens appropriés qui tendent à se développer à l’étranger. Les recherches portent aussi sur les facteurs prédictifs du retour à l’emploi. Les facteurs individuels, liés au patient, en particulier à son état clinique et à ses capacités cognitives, doivent être pris en compte et optimisés, notamment par l’association d’un traitement pharmacologique ajusté et d’interventions psychosociales telle que la remédiation cognitive adaptée aux besoins de la personne. Les dispositifs de soutien à l’insertion professionnelle s’avèrent un déterminant majeur du succès de la réinsertion. Les dispositifs les plus performants, relevant du modèle Place and train, permettent à la majorité des patients (plus de 50 %) d’accéder à l’emploi après 6 à 18 mois d’accompagnement individualisé. Il importe de promouvoir en France le développement de ce type de pratique, mises en œuvre à titre d’expérimentation par des structures militantes, mais qui tardent à se généraliser faute de financements publics dédiés. Cela implique une évolution des pratiques du secteur médico-social, intégrant ces résultats de recherche désormais bien établis et une culture de l’évaluation des pratiques et de leurs résultats. La fonction du conseiller en emploi spécialisé apparaît centrale, et consiste entre autres à coordonner le réseau de soutien à l’insertion sociale et professionnelle de ces patients, comprenant notamment l’employeur et l’équipe soignante.

Metabolic syndrome (MetS) is a highly prevalent and harmful medical disorder often comorbid with psychosis where it can contribute to cardiovascular complications. As immune dysfunction is a key shared component of both MetS and schizophrenia (SZ), this study investigated the relationship between immune alterations and MetS in patients with SZ, whilst controlling the impact of confounding clinical characteristics including psychiatric symptoms and comorbidities, history of childhood maltreatment and psychotropic treatments.

The expression of serotonin type 6 receptor (5-HT6) in limbic and cortical regions of the brain, and its high affinity for atypical antipsychotics suggest that its encoding gene may play a role in the pathogenesis of schizophrenia. We firstly performed a meta-analysis of the C267T polymorphism of the 5-HT6 gene in schizophrenia, based on four different case/control studies, and showed that the allelic distribution is not significantly different between patients and controls, even when taking into account the role of between samples heterogeneity. We then recruited 103 trios (patients with Diognostic and Statistical Manual Mental Disorders, 4th ed. (DSM-IV) diagnosis of schizophrenia and their parents), and investigated the C267T polymorphism of the 5-HT6 receptor gene with regard to family-based association study approach (haplotype relative risk (HRR) and transmission disequilibrium test (TDT)). We found no excess of transmission of one allele from the parents to their affected children, using the HRR (P = 0.60), as well as no evidence for linkage between C267T polymorphism and schizophrenia, using the TDT (P = 0.71). Furthermore, the 267T allele frequency was comparable in the different subgroups defined on age at onset, family history of schizophrenia, treatment response, and subtypes of patients based on positive versus negative predominant symptoms. These data do not support the idea that the 5-HT6 receptor gene plays a major role in the etiopathogenesis of schizophrenia. © 2003 Wiley-Liss, Inc.

We have designed and synthesized original cationic lipids for modulated release of DNA from cationic lipid/DNA complexes. Our rationale was that modulated degradation of the lipids during or after penetration into the cell could improve the trafficking of DNA to the nucleus resulting in increased transgene expression. The new reduction-sensitive lipopolyamines (RSL) harbor a disulfide bridge within different positions in the backbone of the lipids as biosensitive function. A useful synthetic method was developed to obtain, with very good yields and reproducibility, unsymmetrical disulfide-bridged molecules, starting from symmetrical disulfides and thiols. The new lipopolyamines are good candidates as carriers of therapeutic genes for in vivo gene delivery. To optimize the transfection efficiency in these novel series, we have carried out structure−activity relationship studies by placing the disulfide bridge at different positions in the backbone of the cationic lipid and by systematic variation of lipid chain length. Results indicate that the transfection level can be modulated as a function of the location of the disulfide bridge in the molecule. We suggest that an early release of DNA during or after penetration into the cell, probably promoted by reduction of a disulfide bridge placed between the polyamine and the lipid, implies a total loss of transfection efficiency. On the other hand, proper modulation of DNA release by inserting the disulfide bridge between one lipid chain and the rest of the molecule brings about increased transfection efficiency as compared to previously described nondegradable lipopolyamine analogues. Finally, preliminary physicochemical characterization of the complexes demonstrates that DNA release from complexes can be modulated as a function of the surrounding reducing conditions of the complexes and of the localization of the disulfide bridge within the lipopolyamine. Our results suggest that RSL is a promising new approach for gene delivery.

We have designed and synthesized original cationic lipids for gene delivery. A synthetic method on solid support allowed easy access to unsymmetrically monofunctionalized polyamine building blocks of variable geometries. These polyamine building blocks were introduced into cationic lipids. To optimize the transfection efficiency in the novel series, we have carried out structure−activity relationship studies by introduction of variable-length lipids, of variable-length linkers between lipid and cationic moiety, and of substituted linkers. We introduce the concept of using the linkers within cationic lipids molecules as carriers of side groups harboring various functionalities (side chain entity), as assessed by the introduction of a library composed of cationic entities, additional lipid chains, targeting groups, and finally the molecular probes rhodamine and biotin for cellular traffic studies. The transfection activity of the products was assayed in vitro on Hela carcinoma, on NIH3T3, and on CV1 fibroblasts and in vivo on the Lewis Lung carcinoma model. Products from the series displayed high transfection activities. Results indicated that the introduction of a targeting side chain moiety into the cationic lipid is permitted. A primary physicochemical characterization of the DNA/lipid complexes was demonstrated with this leading compound. Selected products from the series are currently being developed for preclinical studies, and the labeled lipopolyamines can be used to study the intracellular traffic of DNA/cationic lipid complexes.

Reinforcement and reward processes have been proposed as being an intermediate link between the risk for alcohol dependence and the gene coding for the dopamine receptor D2 DRD2. This hypothesis remains open to speculation, and personality traits such as impulsiveness, a core dimension in addictive disorders, should also be taken into account. For instance, recent evidence in rats showed that DRD2 antagonists might increase impulsivity in decreasing the value of delayed rewards.

AbstractAimsEstablishing the minimum clinically important difference (MCID) in functioning and cognition is essential to the interpretation of the research and clinical work conducted in bipolar disorders (BD). The present study aimed to estimate the MCID for the Functioning Assessment Short Test (FAST) and a battery of neuropsychological tests in BD.MethodsAnchor-based and distributive methods were used to estimate the MCID for the FAST and cognition using data from a large, multicentre, observational cohort of individuals with BD. The FAST and cognition were linked with the Clinical Global Impressions Scale-Severity (CGI-S) and Global Assessment of Functioning (GAF) using an equipercentile method. The magnitude of the standard error measurement (s.e.m.) provided another estimate of the MCID.ResultsIn total, 570 participants were followed for 2 years. Cross-sectional CGI-S and GAF scores were linked to a threshold ⩽7 on the FAST for functional remission. The MCID for the FAST equalled 8- or 9-points change from baseline using the CGI-S and GAF. One s.e.m.on the FAST corresponded to 7.6-points change from baseline. Cognitive variables insufficiently correlated with anchor variables (all ρ<0.3). One s.e.m.for cognitive variables corresponded to a range of 0.45 to 0.93-s.d.change from baseline.ConclusionsThese findings support the value of the estimated MCID for the FAST and cognition and may be a useful tool to evaluate cognitive and functional remediation effects and improve patient functional outcomes in BD. The CGI-S and GAF were inappropriate anchors for cognition. Further studies may use performance-based measures of functioning instead.

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