Formulation de cas dans la psychose débutante : Quels outils pour le travail en équipe? [Case Formulation in Early Psychosis: What are the Tools for Teamwork?]

Nous présentons d’abord brièvement le programme TIPP et les concepts généraux de la prise en charge précoce dans la psychose débutante. Un des objectifs de l’intervention dans la phase précoce des troubles psychotiques est notamment de proposer des soins spécifiques adaptés à cette phase de la maladie. En début de prise en charge, l’équipe de soins et en particulier le gestionnaire de cas (case manager), chef d’orchestre de la prise en charge, sont confrontés à une quantité importante d’information dont il faut dégager les lignes de forces pour mettre en place une prise en charge adaptée. Cet article propose un modèle qui peut constituer un outil de travail précieux pour les équipes travaillant dans l’intervention précoce pour faire émerger une formulation de cas et synthétiser les situations cliniques des patients, en extraire une histoire qui fasse sens et ainsi faciliter la mise en place d’un projet thérapeutique

Internal and Predictive Validity of the French Health of the Nation Outcome Scales: Need for Future Directions.

The Health of the Nation Outcome Scales (HoNOS) is a widely used measure of health and social functioning of people with mental illness. The goals of this study were to verify the internal validity of the one factor and several four-factor scoring structures and to evaluate the predictive validity of HoNOS items with regards to duration of hospitalization, probability of readmission in the following year and time before readmission. 6175 hospital stays at the department of psychiatry of Lausanne University Hospital were screened and the first HoNOS of each patient was taken into account (N = 2722). Data were analyzed through Confirmatory Factor Analysis (CFA) and the predictive validity of HoNOS items was evaluated with two approaches: item level regressions and latent class analysis (LCA). CFA indicated that the suggested factor structures were not supported by the data. Predictive validity of the 12 items was weak but LCA revealed five distinct and meaningful profiles that were related to length of stay or readmission. HoNOS may be more adapted to the evaluation of patients case-mix rather than to the individual level and concepts such as predictive validity may be more appropriate than internal validity to guide its use

Duration of untreated psychosis: Impact of the definition of treatment onset on its predictive value over three years of treatment.

While reduction of DUP (Duration of Untreated Psychosis) is a key goal in early intervention strategies, the predictive value of DUP on outcome has been questioned. We planned this study in order to explore the impact of three different definition of "treatment initiation" on the predictive value of DUP on outcome in an early psychosis sample. 221 early psychosis patients aged 18-35 were followed-up prospectively over 36 months. DUP was measured using three definitions for treatment onset: Initiation of antipsychotic medication (DUP1); engagement in a specialized programme (DUP2) and combination of engagement in a specialized programme and adherence to medication (DUP3). 10% of patients never reached criteria for DUP3 and therefore were never adequately treated over the 36-month period of care. While DUP1 and DUP2 had a limited predictive value on outcome, DUP3, based on a more restrictive definition for treatment onset, was a better predictor of positive and negative symptoms, as well as functional outcome at 12, 24 and 36 months. Globally, DUP3 explained 2 to 5 times more of the variance than DUP1 and DUP2, with effect sizes falling in the medium range according to Cohen. The limited predictive value of DUP on outcome in previous studies may be linked to problems of definitions that do not take adherence to treatment into account. While they need replication, our results suggest effort to reduce DUP should continue and aim both at early detection and development of engagement strategies

Insight as a social identity process in the evolution of psychosocial functioning in the early phase of psychosis.

Awareness of illness (insight) has been found to have contradictory effects for different functional outcomes after the early course of psychosis. Whereas it is related to psychotic symptom reduction and medication adherence, it is also associated with increased depressive symptoms. In this line, the specific effects of insight on the evolution of functioning over time have not been identified, and social indicators, such as socio-occupational functioning have barely been considered. Drawing from social identity theory we investigated the impact of insight on the development of psychosocial outcomes and the interactions of these variables over time. The participants, 240 patients in early phase of psychosis from the Treatment and Early Intervention in Psychosis Program (TIPP) of the University Hospital of Lausanne, Switzerland, were assessed at eight time points over 3 years. Cross-lagged panel analyses and multilevel analyses were conducted on socio-occupational and general functioning [Social and Occupational Functioning Assessment Scale (SOFAS) and Global Assessment of Functioning (GAF)] with insight, time and depressive symptoms as independent variables. Results from multilevel analyses point to an overall positive impact of insight on psychosocial functioning, which increases over time. Yet the cross-lagged panel analysis did not reveal a systematic positive and causal effect of insight on SOFAS and GAF scores. Depressive symptoms seem only to be relevant in the beginning of the treatment process. Our results point to a complex process in which the positive impact of insight on psychosocial functioning increases over time, even when considering depressive symptoms. Future studies and treatment approaches should consider the procedural aspect of insight

Implication of the glutamate-cystine antiporter xCT in schizophrenia cases linked to impaired GSH synthesis.

xCT is the specific chain of the cystine/glutamate antiporter, which is widely reported to support anti-oxidant defenses in vivo. xCT is therefore at the crossroads between two processes that are involved in schizophrenia: oxidative stress and glutamatergic neurotransmission. But data from human studies implicating xCT in the illness and clarifying the upstream mechanisms of xCT imbalance are still scarce. Low glutathione (GSH) levels and genetic risk in GCLC (Glutamate-Cysteine Ligase Catalytic subunit), the gene of limiting synthesizing enzyme for GSH, are both associated with schizophrenia. In the present study, we aimed at determining if xCT regulation by the redox system is involved in schizophrenia pathophysiology. We assessed whether modulating GCLC expression impact on xCT expression and activity (i) in fibroblasts from patients and controls with different GCLC genotypes which are known to affect GCLC regulation and GSH levels; (ii) in rat brain glial cells, i.e., astrocytes and oligodendrocytes, with a knock-down of GCLC. Our results highlight that decreased GCLC expression leads to an upregulation of xCT levels in patients' fibroblasts as well as in astrocytes. These results support the implication of xCT dysregulation in illness pathophysiology and further indicate that it can result from redox changes. Additionally, we showed that these anomalies may already take place at early stages of psychosis and be more prominent in a subgroup of patients with GCLC high-risk genotypes. These data add to the existing evidence identifying the inflammatory/redox systems as important targets to treat schizophrenia already at early stages. ANTIOXIDANT DEFICIT INCREASES A KEY NEUROTRANSMITTER TRANSPORTER: Deficit of antioxidant synthesis in schizophrenia leads to oxidative stress and changes in neurotransmitter transporter. Led by Kim Do, a team of researchers from Lausanne University in Switzerland investigated the role of the cell-surface transport protein xCT in schizophrenia. They found that an enzyme responsible for antioxidant production is disturbed in patients. This leads to decreased antioxidant levels and consequently to oxidative stress-i.e. the accumulation of reactive oxygen molecules, damaging the cells component and impairing cell functioning-which in turn affects the functioning of the antioxidant pathway, including xCT. xCT, which exports the neurotransmitter glutamate, is thus overproduced in schizophrenia. The resulting increase of neurotransmitter activity, alongside the increase in oxidative stress, is thought to play a major role in the pathophysiology of schizophrenia, including at early stages of the disease

Genetics-Based Population Pharmacokinetics and Pharmacodynamics of Risperidone in a Psychiatric Cohort.

BACKGROUND: High interindividual variability in plasma concentrations of risperidone and its active metabolite, 9-hydroxyrisperidone, may lead to suboptimal drug concentration. OBJECTIVE: Using a population pharmacokinetic approach, we aimed to characterize the genetic and non-genetic sources of variability affecting risperidone and 9-hydroxyrisperidone pharmacokinetics, and relate them to common side effects. METHODS: Overall, 150 psychiatric patients (178 observations) treated with risperidone were genotyped for common polymorphisms in NR1/2, POR, PPARα, ABCB1, CYP2D6 and CYP3A genes. Plasma risperidone and 9-hydroxyrisperidone were measured, and clinical data and common clinical chemistry parameters were collected. Drug and metabolite concentrations were analyzed using non-linear mixed effect modeling (NONMEM(®)). Correlations between trough concentrations of the active moiety (risperidone plus 9-hydroxyrisperidone) and common side effects were assessed using logistic regression and linear mixed modeling. RESULTS: The cytochrome P450 (CYP) 2D6 phenotype explained 52% of interindividual variability in risperidone pharmacokinetics. The area under the concentration-time curve (AUC) of the active moiety was found to be 28% higher in CYP2D6 poor metabolizers compared with intermediate, extensive and ultrarapid metabolizers. No other genetic markers were found to significantly affect risperidone concentrations. 9-hydroxyrisperidone elimination was decreased by 26% with doubling of age. A correlation between trough predicted concentration of the active moiety and neurologic symptoms was found (p = 0.03), suggesting that a concentration >40 ng/mL should be targeted only in cases of insufficient, or absence of, response. CONCLUSIONS: Genetic polymorphisms of CYP2D6 play an important role in risperidone, 9-hydroxyrisperidone and active moiety plasma concentration variability, which were associated with common side effects. These results highlight the importance of a personalized dosage adjustment during risperidone treatment

Trajectory and predictors of quality of life in first episode psychotic mania.

BACKGROUND: Little is known about the trajectory of quality of life (QoL) following a first episode of psychotic mania in bipolar disorder (BD). This 18-month longitudinal study investigated the trajectory of QoL, and the influence of premorbid adjustment and symptoms on 18-month QoL in a cohort of young people experiencing a first episode of psychotic mania. METHODS: As part of an overarching clinical trial, at baseline, sixty participants presenting with a first episode of psychotic mania (BD Type 1 - DSM-IV) completed symptomatic and functional assessments in addition to the Premorbid Adjustment Scale - General Subscale. Symptom measures were repeated at 18-month follow up. QoL was rated using the Quality of Life Scale (QLS) at designated time points. RESULTS: Mean QLS scores at initial measurement (8 weeks) were 61% of the maximum possible score, increasing significantly to 70% at 12 months, and 71.2% at 18-month follow-up. Premorbid adjustment and 18-month depressive symptoms were significantly associated with QoL at 18-month follow-up. LIMITATIONS: Study limitations include the small sample size, inclusion of participants with psychotic mania only, use of measures originally designed for use with schizophrenia spectrum disorders, and lack of premorbid or baseline measurement of QoL. CONCLUSIONS: Results suggest that QoL can be maintained early in BD, and reinforce the importance of assertively treating depressive symptoms throughout the course of this disorder. The emergence of a link between premorbid adjustment and poorer QoL in this cohort highlights the importance of assessing facets of adjustment when planning psychological interventions

Age at the time of onset of psychosis: A marker of specific needs rather than a determinant of outcome?

While there is suggestion that early onset of psychosis is a determinant of outcome; knowledge regarding correlates of later onset age is more limited. This study explores the characteristics of patients developing psychosis after age 26, towards the end of the usual age range of early intervention programs, in order to identify potential specific needs of such patients. Two hundred and fifty-six early psychosis patients aged 18-35 were followed-up prospectively over 36 months. Patients with onset after 26 ("later onset", LO) were compared to the rest of the sample. LO patients (32% of the sample) had shorter DUP, were less likely to be male, had better premorbid functioning and were more likely to have been exposed to trauma. They had greater insight at presentation and less negative symptoms overall. The trajectories for positive and depressive symptoms were similar in both groups. Evolution of functional level was similar in both groups, but while LO patients recovered faster, they were significantly less likely to return to premorbid functional level. Later psychosis onset correlates with better premorbid functioning and higher rate of trauma exposure; the latter should therefore be a treatment focus in such patients. LO patients were less likely to return to premorbid functional level, which suggests that current treatment strategies may not be efficient to help patients maintain employment. The possibility of distinct illness mechanisms according to onset age and the more central role for trauma in patients with onset after age 26 needs to be further explored