4th European conference on schizophrenia research: together for better treatment and care
European Archives of Psychiatry and Clinical Neuroscience
Clinical research over the past several years has increasingly revealed marked heterogeneity and excessive co-morbidity of psychiatric disorders as currently defined. Recent studies have also demonstrated significant overlaps in genetic risk across the spectrum of psychotic disorders, as well as across mood-anxiety disorders. These issues represent barriers to accurate diagnosis and the development of appropriately focused treatments. In response to such concerns, the National Institute of
... l Health (NIMH) developed the Research Domain Criteria project (RDoC), to "develop, for research purposes, new ways of classifying mental disorders based on dimensions of observable behavior and neurobiological measures." This talk will summarize the rationale and current status of RDoC, with an emphasis on how research within the RDoC framework can contribute to new ways of parsing the spectrum of psychotic disorders and to the development of more precisely targeted preventive and treatment interventions. Abstract: Modern psychiatric classifications avoid the term "disease" and instead describe "disorders" of mental functioning. However, the S8 Eur Arch Psychiatry Clin Neurosci (2013) 263 (Suppl 1):S7-S111 • Risk-profile before and during treatment • Drop-out rate, compliance, adherence, illness severity, patient and family satisfaction, global functioning, etc. Furthermore the patients are compared to a control sample of patients who are out of the catchment area. Conclusion: First results dealing with the above named parameters are very promising and will be presented beside a case history. Objective: To conceptualize, adapt and apply a multimodal treatment programme for schizophrenia patients as a follow-up after discharge from compulsory general psychiatric hospitalization. To assess the feasibility of applying the intervention, and to analyse its effectiveness and efficacy on the primary endpoint of compulsory readmission due to endangering behaviour and multi-domain secondary endpoints. Methods: A total of 79 subjects with schizophrenia, schizoaffective or maniac disorder (ICD-10), who have received compulsory general psychiatric hospital treatment, are to be enrolled in a prospective outpatient intervention trial. The intervention is multimodal, includes patient tracking and is adaptable to individual needs. It comprises psychiatric, psychotherapeutic, social support and risk management modules. The intervention phase is 6 months, followed by a 6-month catamnestic follow-up. At baseline, post-intervention and post-follow-up, standardized variables of re-admission, anamnestic key information, aggressive behaviour, delinquency, psychopathology, social functioning, social and neuro-cognition are assessed and compared to a patient group receiving treatment as usual at a partner hospital. Primary endpoint is the rate of readmission to general psychiatric hospital care. Secondary analyses regard respective rates and predictors of violent behaviour, delinquency and forensic detention. Results: Preliminary interim analysis of 77 screened patients shows good feasibility of study and treatment design with a recruitment rate of 57 % and an adherence rate of 94 %. Aggressive behaviour having led to initial general psychiatric hospital treatment is largely moderate with preponderance of threatening behaviour or aggression towards objects. Psychiatric comorbidity is mostly limited to substance abuse. So far, the total readmission rate is below 50 %, the rate of compulsory readmission is 12.5 %. The total amount of intervention S10 Eur Arch Psychiatry Clin Neurosci (2013) 263 (Suppl 1):S7-S111 Conclusion: A proportion of patients with schizophrenia may have pathogenic antibodies against the NMDA receptor, and be treatable with immunotherapy. Abstract not received in due time. S-04-004 The mild encephalitis hypothesis of schizophrenia updated Objective: Schizophrenia seems to be a heterogeneous disorder. Infections and autoimmune disorders are risk factors. Low level neuroinflammation (LLNI) may be involved. Methods: According to the mild encephalitis (ME) hypothesis, LLNI represents the core pathogenetic mechanism in a schizophrenia subgroup, possibly triggered by infections, autoimmunity, toxicity, or trauma. Results: A 'late hit' and gene-environment interaction are required to explain major findings about schizophrenia, and both aspects would be consistent with the ME hypothesis. Schizophrenia risk genes stay rather constant within populations despite a resulting low number of progeny, suggesting advantages associated with risk genes, e.g., an improved immune response, which may act protectively within changing environments. Specific schizophrenic symptoms may arise with instances of LLNI when certain brain functional systems are involved, in addition to being shaped by pre-existing liability factors. Prodrome phase and the transition to a diseased status may be related to LLNI processes emerging and varying over time. Contributing factors are genes, environment, and immune system. ME could represent a common pathogenetic link for the distributed brain dysfunction, dysconnectivity, and brain structural abnormalities observed in schizophrenia. Preliminary criteria for subgrouping neurodevelopmental, genetic, ME, and other types of schizophrenias are proposed. A rare example of ME schizophrenia may be observed in Borna disease virus infection. LLNI may include dysfunction of the blood-brain barrier, the blood-CSF barrier, CNSendogenous immunity. The volume transmission mode is linked to CSF signalling, which may extend into peripheral tissues via the CSF outflow pathway along brain nerves and peripheral nerves, and it may explain the peripheral topology of some neuronal dysfunctions found, like in olfactory dysfunction, dysautonomia, and even pathology in peripheral tissues, i.e., the muscle lesions found in 50 % of cases. Conclusion: Considering investigations of CSF, the ME schizophrenia subgroup may constitute approximately 40 % of cases. Objective: During the past two decades, the construct of a clinical high risk (HR) state for psychosis, has evolved to capture the prepsychotic phase, describing people presenting with potentially prodromal symptoms. The aim of this presentation is to reframe the diagnostic, prognostic and treatment validity data of the HR state. Methods: Conceptual review of HR studies addressing inclusion criteria, epidemiology, transition criteria, outcomes, clinical and functional characteristics, neurocognition, neuroimaging, predictors of psychosis development, treatment trials, socioeconomic aspects, nosography and future challenges in the field. This is supported by recent meta-analyses in the field. Results: Independent of the psychometric instrument employed to diagnose HR subjects, there is meta-analytical mean transition risk of 18 % (95 % CI 12-25) after 6 months of follow-up, 22 % (95 % CI I. Kelleher (Royal College of Surgeons in Ireland, Objective: Antipsychotic drugs have been used for more than a half century. The aim of the present analyses were to describe the course of positive and negative symptoms during inpatient treatment and examine remission and response rates under routine clinical care conditions. Furthermore, we aimed to examine the predictive validity of early improvement and to identify the criterion that bests define early improvement. Methods: Within the framework of the German Research Network on Schizophrenia 218 patients suffering from schizophrenia were assessed with the Positive and Negative Syndrome Scale (PANSS) at admission and at biweekly intervals until discharge from hospital. Patients were treated under naturalistic conditions. Remission was defined according to the symptom-severity component of the consensus criteria (Remission in Schizophrenia Working Group) as a rating of three or less in the relevant PANSS items at discharge, and response as a reduction of at least 20 % in the PANSS total score from admission to discharge. Results: The mean duration of inpatient treatment was 54.8 days. Of the total sample, 78.5 % achieved the criteria for response and 44.6 % those for remission. Mean PANSS total scores decreased from 72.4 at admission to 52.5 at discharge. A reduction in PANSS total scores was found from visit to visit, up to week 8. The most pronounced decline was observed within the first 2 weeks of treatment. Receiver operating characteristic (ROC) analyses showed that early improvement (reduction of the PANSS total score within the first 2 weeks of treatment) predicts remission (AUC = 0.659) at discharge. A 20 % reduction in the PANSS total score within the first 2 weeks was the most accurate cut-off for the prediction of remission (total accuracy: 65 %; sensitivity: 53 %; specificity: 76 %). Conclusion: The treatment under naturalistic conditions of "real world" patients suffering from schizophrenia appears to be beneficial in terms of clinical effectiveness. However, a considerable number of patients despite achieving response fail to achieve symptom remission during inpatient treatment, underlining the need for optimizing current available treatment. Furthermore, the findings of clinical drug trials that early improvement is a predictor of subsequent treatment response were replicated in a naturalistic sample. Further studies should examine whether patients without early improvement benefit from an early change of antipsychotic medication. Policy of full disclosure: M. Jäger received remunerations and financial support for congresses from AstraZeneca, Eli Lilly und Janssen-Cilag. S-06-003 The development of multiple antipsychotic combination treatment in comparison between European countries: findings from the AMSP project A. Konstantinidis (Div. Objective: Psychotropic polypharmacy, although related with a higher risk for adverse drug reactions (ADR) and lacking data regarding efficacy, is widely used in routine clinical practice. Antipsychotic (AP) polypharmacy, the combination of two or more APs, in schizophrenia is practiced around the world, although the percentage varies among countries, continents and therapeutic setting (inpatient/ outpatient). Methods: The AMSP study is a drug safety program for the continuous assessment of severe ADR in psychiatric inpatients under the naturalistic conditions of routine clinical treatment. Today, 20 years after the initiation of AMSP, 60 institutions from Austria, Germany and Switzerland participate in the program. On two reference days per hospital and per year, the following data are recorded for all patients on the wards under AMSP surveillance: all drugs applied on that day with the daily dosage for psychotropic drugs, ICD diagnosis, age, and sex. Data is stored at the study centre in Hannover. Results: From 2003 to 2011 we collected reference-day-data from 6986 inpatients being treated for a F20 ICD-10 diagnosis. Psychotropic monotherapy was found only in 23.38 % of our sample. Most inpatients in our sample received one AP (52.58 %), although still a large proportion of them received two (35.26 %) or more APs. The percentage of inpatients being prescribed one AP-agent was more common in Switzerland (61.34 %) than in Germany (49.62) or Austria (40.23 %). Clozapine and olanzapine were most common APs prescribed as monotherapy in our sample. Combinations of two APs showed great variety and differences between countries in preference of AP-combinations could be seen. In prescriptions with two APagents clozapine (27.2 %) and risperidone (21.61 %) were most commonly found. Conclusion: Since AP polypharmacy is common practice among clinicians, future guidelines should give guidance regarding prescription of rational combinations in the treatment of schizophrenia. Therefore further studies on seeming putative combinations of APtreatment are needed. Policy of full disclosure: Have received honoraria from Affiris, AstraZeneca, Novartis, Pfizer and Servier, served as consultant for AstraZeneca, and as a speaker for AstraZeneca, Bristol-Myers Squib and Janssen-Cilag.