Suchergebnisse

Social withdrawal is one of the first and common signs of early social dysfunction in a number of important neuropsychiatric disorders, likely because of the enormous amount and complexity of brain processes required to initiate and maintain social relationships (Adolphs, 2009). The Psychiatric Ratings using Intermediate Stratified Markers (PRISM) project focusses on the shared and unique neurobiological basis of social withdrawal in schizophrenia, Alzheimer and depression. In this paper, we discuss the working definition of social withdrawal for this study and the selection of objective and subjective rating scales to assess social withdrawal chosen or adapted for this project. We also discuss the MRI and EEG paradigms selected to study the systems and neural circuitry thought to underlie social functioning and more particularly to be involved in social withdrawal in humans, such as the social perception and the social affiliation networks. A number of behavioral paradigms were selected to assess complementary aspects of social cognition. Also, a digital phenotyping method (a smartphone application) was chosen to obtain real-life data. ; This work was supported by the European Union Horizon 2020 Innovative Medicines Initiative 2 Joint Undertaking grant 115916 for the project 'Psychiatric ratings using intermediate stratified markers'

BACKGROUND: The catechol-O-methyltransferase (COMT) enzyme plays a crucial role in dopamine degradation, and the COMT Val158Met polymorphism (rs4680) is associated with significant differences in enzymatic activity and consequently dopamine concentrations in the prefrontal cortex. Multiple studies have analyzed the COMT Val158Met variant in relation to antipsychotic response. Here, we conducted a meta-analysis examining the relationship between COMT Val158Met and antipsychotic response. METHODS: Searches using PubMed, Web of Science, and PsycInfo databases (03/01/2015) yielded 23 studies investigating COMT Val158Met variation and antipsychotic response in schizophrenia and schizo-affective disorder. Responders/nonresponders were defined using each study's original criteria. If no binary response definition was used, authors were asked to define response according to at least 30% Positive and Negative Syndrome Scale score reduction (or equivalent in other scales). Analysis was conducted under a fixed-effects model. RESULTS: Ten studies met inclusion criteria for the meta-analysis. Five additional antipsychotic-treated samples were analyzed for Val158Met and response and included in the meta-analysis (ntotal=1416). Met/Met individuals were significantly more likely to respond than Val-carriers (P=.039, ORMet/Met=1.37, 95% CI: 1.02-1.85). Met/Met patients also experienced significantly greater improvement in positive symptoms relative to Val-carriers (P=.030, SMD=0.24, 95% CI: 0.024-0.46). Posthoc analyses on patients treated with atypical antipsychotics (n=1207) showed that Met/Met patients were significantly more likely to respond relative to Val-carriers (P=.0098, ORMet/Met=1.54, 95% CI: 1.11-2.14), while no difference was observed for typical-antipsychotic-treated patients (n=155) (P=.65). CONCLUSIONS: Our findings suggest that the COMT Val158Met polymorphism is associated with response to antipsychotics in schizophrenia and schizo-affective disorder patients. This effect may be more pronounced for atypical antipsychotics. ; C.C.Z. is supported by the Brain and Behavior Research Foundation, American Foundation for Suicide Prevention and Eli Lilly. D.F. is supported by the Vanier Canada Graduate Scholarship. D.J.M. has been or is supported by the Canadian Institute of Health Research (CIHR) Operating Grant: "Genetics of antipsychotic-induced metabolic syndrome," Michael Smith New Investigator Salary Prize for Research in Schizophrenia, NARSAD Independent Investigator Award by the Brain & Behavior Research Foundation, and Early Researcher Award from Ministry of Research and Innovation of Ontario. E.H. is supported by the Canada Graduate Scholarship. H.Y.M. has grant support from Sumitomo Dainippon, Sunovion, Boehringer Ingelheim, Eli Lilly, Janssen, Reviva, Alkermes, Auspex, and FORUM. J.A.L. has received research funding from Alkermes, Biomarin, EnVivo/Forum, Genentech, and Novartis. J.L.K. is supported the CIHR grant "Strategies for gene discovery in schizophrenia: subphenotypes, deep sequencing and interaction." J.R.B. is supported by NIH grant MH083888. A.K.T. is supported by a NARSAD Young Investigator Award. J.S. is supported by a Pfizer independent grant. P.M. receives salary from Clinica Universidad de Navarra and has received research grants from the Ministry of Education (Spain), the Government of Navarra (Spain), the Spanish Foundation of Psychiatry and Mental Health, and Astrazeneca. S.G. is supported by the Ningbo Medical Technology Project Fund (No. 2004050), the Natural Science Foundation of Ningbo (No. 2009A610186, No. 2013A610249), and the Zhejiang Provincial Medical and Health Project Fund (No. 2015127713). S.G.P. has received research support from Otsuka, Lundbeck, FORUM, and Alkermes.