Primary care and the early phases of schizophrenia in the Czech Republic

Aim - To explore knowledge, treatment setting, attitudes and needs associated with patients in early phases of psychosis among general practitioners (GPs) in Prague, andto compare results with GPs from 6 countries participating in the International GP Study (IGPS) on Early Psychosis (Canada, Australia, New Zealand, England, Norway,Austria). Methods - Survey questionnaires were mailed to 648 GPs in the city of Prague. Results - The response rate was 19.9%. Prague GPs showed significantly lower diagnostic knowledge of early phases of psychosis compared to their international colleagues. They frequently indicated depression/anxiety and somatic complaints as early warnings of psychosis. They more often considered their behaviour to be problematic and more commonly handed them over to specialists. The majority of Prague GPs wished specialized outpatient services for low-threshold referrals of such patients. Conclusions - Along the mental health reforms in the Czech Republic which emphasis the role of primary care, GPs' knowledge of the early warning signs of psychosis needs to be improved. Declaration of Interest: The study was supported by an unrestricted grant from Sanofi-Synthélabo SA, Switzerland, to the principal investigators of the IGPS (AES, DU). The authors have stated that there are none; all authors are independent from the funding body and the views expressed in this paper have not been influenced by the funding sourc

Primary care and the early phases of schizophrenia in the Czech Republic

Aim – To explore knowledge, treatment setting, attitudes and needs associated with patients in early phases of psychosis among general practitioners (GPs) in Prague, andto compare results with GPs from 6 countries participating in the International GP Study (IGPS) on Early Psychosis (Canada, Australia, New Zealand, England, Norway,Austria). Methods – Survey questionnaires were mailed to 648 GPs in the city of Prague. Results – The response rate was 19.9%. Prague GPs showed significantly lower diagnostic knowledge of early phases of psychosis compared to their international colleagues. They frequently indicated depression/anxiety and somatic complaints as early warnings of psychosis. They more often considered their behaviour to be problematic and more commonly handed them over to specialists. The majority of Prague GPs wished specialized outpatient services for low-threshold referrals of such patients. Conclusions – Along the mental health reforms in the Czech Republic which emphasis the role of primary care, GPs' knowledge of the early warning signs of psychosis needs to be improved

Sur la première ligne : sondage pour un partage. Les omnipraticiens et la schizophrénie

Contexte : Les omnipraticiens (MFs) jouent un rôle prépondérant dans le traitement des patients atteints de schizophrénie. Buts : Découvrir le nombre de patients atteints de schizophrénie qui sont traités par les MFs ; les besoins et attitudes des MFs, leurs connaissances en matière de diagnostic, et le traitement qu’ils prodiguent. Méthodologie : Un sondage postal a été conduit auprès de MFs du Québec choisis de façon aléatoire. Résultats : Un total de 1 003 MFs ont répondu au sondage. Parmi eux, un faible pourcentage a à rencontrer une schizophrénie débutante et les MFs désirent être plus informés sur l’accessibilité aux services des spécialistes. Les résultats objectivés aux questions portant sur les diagnostics et les connaissances sur les traitements sont inconsistants. La majorité des MFs traite les premiers épisodes psychotiques avec des antipsychotiques. Seulement un tiers d’entre eux proposent de maintenir le traitement après un premier épisode psychotique, conformément aux recommandations internationales et au récent guide de pratique canadien qui préconisent au moins de 6 à 12 mois de traitement après la réponse clinique partielle ou complète. Le temps consacré par les MFs masculins à un premier contact s’étale entre 10 et 20 minutes, tandis que 80 % des MFs femmes y consacrent au moins 20 minutes Les effets secondaires des antipsychotiques les plus préoccupants sont les gains de poids avant les signes neurologiques. Conclusion : un certain nombre de données de ce sondage devraient être reprises par les différentes associations professionnelles et gouvernementales, afin de bonifier la place des MFs dans un plan de santé à l’égard de la schizophrénie.Context: General practitioners (GP) play a preponderant role in the treatment of patients suffering of schizophrenia. Objectives: Discovering the number of patients with schizophrenia who are treated by GPs ; the needs and attitudes of GPs, their knowledge concerning diagnosis, and the treatment they provide. Methodology: A postal survey was conducted with Quebec GPs who were randomly chosen. Results: A total of 1 003 GPs have participated in the survey. Among them, a small percentage have to treat an early onset schizophrenia and the GPs have expressed their wish to be more informed on the accessibility of specialized services. Results pertaining to questions on diagnoses and knowledge on treatments are inconsistent. The majority of GPs treat the first psychotic episodes with antipsychotic medication. Only a third of GPs surveyed propose maintaining the treatment after a first psychotic episode, in accordance with international recommendations and the recent Canadian guidelines on practices that recommends at least 6 to 12 months of treatment after a partial or complete clinical response. Time given by male GPs to a first contact varies between 10 and 20 minutes, while 80 % of female GPs spend at least 20 minutes. The adverse effects of antipsychotic medication that raise most concern is weight gain before neurological signs. Conclusion: some of this survey’s data should be considered by various professional and governmental associations, in order to improve the place of GPs in a health plan destined to treat schizophrenia.Contexto: Los médicos familiares (MFs) desempeñan un papel preponderante en el tratamiento de pacientes que sufren de esquizofrenia. Objetivos: Descubrir el número de pacientes que sufren de esquizofrenia y que son tratados por los MFs; las necesidades y actitudes de los MFs, sus conocimientos en materia de diagnóstico y el tratamiento que ofrecen. Metodología: Se realizó una encuesta por correo con los MFs de Quebec elegidos de modo aleatorio. Resultados: Un total de 1,003 MFs respondieron a la encuesta. Entre ellos, un porcentaje bajo han encontrado una esquizofrenia inicial y los MFs desean estar más informados sobre la accesibilidad a los servicios de los especialistas. Los resultados asociados a las preguntas sobre los diagnósticos y los conocimientos acerca de los tratamientos son inconsistentes. La mayoría de los MFs tratan los primeros episodios psicóticos con antipsicóticos. Solamente un tercio de ellos propone mantener el tratamiento después de un primer episodio psicótico, conforme a las recomendaciones internacionales y a la reciente guía de práctica canadiense que preconiza al menos de 6 a 12 meses de tratamiento después de la respuesta clínica parcial o completa. El tiempo consagrado por los MFs masculinos en un primer contacto se extiende de 10 a 20 minutos, mientras que el 80% de los MFs femeninas consagran al menos 20 minutos. Los efectos secundarios de los antipsicóticos más preocupantes son el aumento de peso antes que los signos neurológicos. Conclusión: un cierto número de datos de esta encuesta deberían ser retomados por las diferentes asociaciones profesionales y gubernamentales a fin de bonificar el lugar de los MFs en un plan de salud con respecto a la esquizofrenia.Contexto: os clínicos gerais (médicos de família - MFs) representam um papel preponderante no tratamento dos pacientes que sofrem de esquizofrenia. Objetivos: descobrir o número de pacientes que sofrem de esquizofrenia que são tratados por MFs, as necessidades e atitudes dos MFs, seus conhecimentos em matéria de diagnóstico, e o tratamento que prescrevem. Metodologia: uma sondagem postal foi realizada com MFs do Quebec, escolhidos de maneira aleatória. Resultados: um total de 1.003 MFs responderam à sondagem. Dentre eles, uma pequena porcentagem encontrou uma esquizofrenia inicial e os MFs desejam ser melhor informados sobre a acessibilidade aos serviços de especialistas. Os resultados obtidos com as questões sobre os diagnósticos e os conhecimentos sobre os tratamentos são inconsistentes. A maioria dos MFs trata os primeiros episódios psicóticos com antipsicóticos. Apenas um terço dentre eles propõe manter o tratamento após um primeiro episódio psicótico, conforme as recomendações internacionais e o recente guia de prática canadense, que preconiza pelo menos 6 a 12 meses de tratamento após a resposta clínica parcial ou completa. O tempo dedicado pelos MFs masculinos a um primeiro contato dura entre 10 e 20 minutos, ao passo que 80% das MFs femininas consagram, pelo menos, 20 minutos. O efeito colateral dos antipsicóticos mais inquietante é o aumento de peso antes dos sinais neurológicos. Conclusão: um certo número de dados desta sondagem deverão ser retomados por diferentes associações profissionais e governamentais, a fim de melhorar a importância dos MFs em um plano de saúde com respeito à esquizofrenia

Effects of risperidone on auditory event-related potentials in schizophrenia

Schizophrenia is associated with cognitive deficits for which treatments remain elusive. The effects of risperidone (an antipsychotic differing in some of its pharmacological properties from typical agents) on cognitive deficits have not been extensively investigated. Mismatch negativity (MMN), N2 and P3 are cognitive event-related potentials that index preattentive (MMN) and attention-dependent information processing (N2, P3) and provide a measure of cognitive deficits in schizophrenia. The effects of risperidone treatment on MMN, N2 and P3 generation in chronic schizophrenic patients were investigated in an open- label, uncontrolled study. Risperidone treatment significantly reduced psychotic symptoms. It was associated with a decrease of peak latencies, particularly pronounced for P3. However, it did not significantly affect abnormal MMNor P3 amplitudes. The results suggest an effect of risperidone on processing speed, particularly in attention-dependent tasks. These results are in agreement with findings in recent studies on the cognitive effects of risperidone

Help-seeking pathways in early psychosis

INTRODUCTION: Understanding the help-seeking pathways of patients with a putative risk of developing psychosis helps improving development of specialised care services. This study aimed at obtaining information about: type of health professionals contacted by patients at putative risk for psychosis on their help-seeking pathways; number of contacts; type of symptoms leading to contacts with health professionals; interval between initial contact and referral to a specialised outpatient service. METHOD: The help-seeking pathways were assessed as part of a prospective study in 104 patients with suspected at-risk states for psychosis. RESULTS: The mean number of contacts prior to referral was 2.38. Patients with psychotic symptoms more often contacted mental health professionals, whereas patients with insidious and more unspecific features more frequently contacted general practitioners (GPs). CONCLUSIONS: GPs have been found to under-identify the insidious features of emerging psychosis (Simon et al. (2005) Br J Psychiatry 187:274–281). The fact that they were most often contacted by patients with exactly these features calls for focussed and specialised help for primary care physicians. Thus, delays along the help-seeking pathways may be shortened. This may be of particular relevance for patients with the deficit syndrome of schizophrenia

An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype

AbstractBackgroundThe genetics of depression has been explored in genome-wide association studies that focused on either major depressive disorder or depressive symptoms with mostly negative findings. A broad depression phenotype including both phenotypes has not been tested previously using a genome-wide association approach. We aimed to identify genetic polymorphisms significantly associated with a broad phenotype from depressive symptoms to major depressive disorder.MethodsWe analyzed two prior studies of 70,017 participants of European ancestry from general and clinical populations in the discovery stage. We performed a replication meta-analysis of 28,328 participants. Single nucleotide polymorphism (SNP)-based heritability and genetic correlations were calculated using linkage disequilibrium score regression. Discovery and replication analyses were performed using a p-value-based meta-analysis. Lifetime major depressive disorder and depressive symptom scores were used as the outcome measures.ResultsThe SNP-based heritability of major depressive disorder was 0.21 (SE = 0.02), the SNP-based heritability of depressive symptoms was 0.04 (SE = 0.01), and their genetic correlation was 1.001 (SE = 0.2). We found one genome-wide significant locus related to the broad depression phenotype (rs9825823, chromosome 3: 61,082,153, p = 8.2 × 10–9) located in an intron of the FHIT gene. We replicated this SNP in independent samples (p = .02) and the overall meta-analysis of the discovery and replication cohorts (1.0 × 10–9).ConclusionsThis large study identified a new locus for depression. Our results support a continuum between depressive symptoms and major depressive disorder. A phenotypically more inclusive approach may help to achieve the large sample sizes needed to detect susceptibility loci for depression

Genome-wide interaction study of a proxy for stress-sensitivity and its prediction of major depressive disorder

Individual response to stress is correlated with neuroticism and is an important predictor of both neuroticism and the onset of major depressive disorder (MDD). Identification of the genetics underpinning individual differences in response to negative events (stress-sensitivity) may improve our understanding of the molecular pathways involved, and its association with stress-related illnesses. We sought to generate a proxy for stress-sensitivity through modelling the interaction between SNP allele and MDD status on neuroticism score in order to identify genetic variants that contribute to the higher neuroticism seen in individuals with a lifetime diagnosis of depression compared to unaffected individuals. Meta-analysis of genome-wide interaction studies (GWIS) in UK Biobank (N = 23,092) and Generation Scotland: Scottish Family Health Study (N = 7,155) identified no genome-wide significance SNP interactions. However, gene-based tests identified a genome-wide significant gene, ZNF366, a negative regulator of glucocorticoid receptor function implicated in alcohol dependence (p = 1.48x10-7; Bonferroni-corrected significance threshold p < 2.79x10-6). Using summary statistics from the stress-sensitivity term of the GWIS, SNP heritability for stress-sensitivity was estimated at 5.0%. In models fitting polygenic risk scores of both MDD and neuroticism derived from independent GWAS, we show that polygenic risk scores derived from the UK Biobank stress-sensitivity GWIS significantly improved the prediction of MDD in Generation Scotland. This study may improve interpretation of larger genome-wide association studies of MDD and other stress-related illnesses, and the understanding of the etiological mechanisms underpinning stress-sensitivity

Identification of common genetic risk variants for autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD

Hair Cortisol in Twins : Heritability and Genetic Overlap with Psychological Variables and Stress-System Genes

A. Palotie on työryhmän jäsen.Hair cortisol concentration (HCC) is a promising measure of long-term hypothalamus-pituitary-adrenal (HPA) axis activity. Previous research has suggested an association between HCC and psychological variables, and initial studies of inter-individual variance in HCC have implicated genetic factors. However, whether HCC and psychological variables share genetic risk factors remains unclear. The aims of the present twin study were to: (i) assess the heritability of HCC; (ii) estimate the phenotypic and genetic correlation between HPA axis activity and the psychological variables perceived stress, depressive symptoms, and neuroticism; using formal genetic twin models and molecular genetic methods, i.e. polygenic risk scores (PRS). HCC was measured in 671 adolescents and young adults. These included 115 monozygotic and 183 dizygotic twin-pairs. For 432 subjects PRS scores for plasma cortisol, major depression, and neuroticism were calculated using data from large genome wide association studies. The twin model revealed a heritability for HCC of 72%. No significant phenotypic or genetic correlation was found between HCC and the three psychological variables of interest. PRS did not explain variance in HCC. The present data suggest that HCC is highly heritable. However, the data do not support a strong biological link between HCC and any of the investigated psychological variables.Peer reviewe

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe