Suchergebnisse

Background: The size and increasing burden of disease due to mental disorders in Europe poses substantial challenges to its population and to the health policy of the European Union. This warrants a specific research agenda concerning clinical mental health research as one of the cornerstones of sustainable mental health research and health policy in Europe. The aim of this research was to identify the top priorities needed to address the main challenges in clinical research for mental disorders. Methods: The research was conducted as an expert survey and expert panel discussion during a scientific workshop. Results: Eighty-nine experts in clinical research and representing most European countries participated in this survey. Identified top priorities were the need for new intervention studies, understanding the diagnostic and therapeutic implications of mechanisms of disease, and research in the field of somatic-psychiatric comorbidity. The "subjectivity gap" between basic neuroscience research and clinical reality for patients with mental disorders is considered the main challenge in psychiatric research, suggesting that a shift in research paradigms is required. Conclusion: Innovations in clinical mental health research should bridge the gap between mechanisms underlying novel therapeutic interventions and the patient experience of mental disorder and, if present, somatic comorbidity. Clinical mental health research is relatively underfunded and should receive specific attention in Horizon 2020 funding programs.

Although addiction develops in a considerable number of regular cocaine users, molecular risk factors for cocaine dependence are still unknown. It was proposed that establishing drug use and memory formation might share molecular and anatomical pathways. Alpha-Ca2+/calmodulin-dependent protein kinase-II (alpha CaMKII) is a key mediator of learning and memory also involved in drug-related plasticity. the autophosphorylation of aCaMKII was shown to accelerate learning. Thus, we investigated the role of aCaMKII autophosphorylation in the time course of establishing cocaine use-related behavior in mice. We found that alpha CaMKII autophosphorylation-deficient alpha CaMKIIT286A mice show delayed establishment of conditioned place preference, but no changes in acute behavioral activation, sensitization or conditioned hyperlocomotion to cocaine (20 mg kg(-1), intraperitoneal). in vivo microdialysis revealed that alpha CaMKIIT286A mice have blunted dopamine (DA) and blocked serotonin (5-HT) responses in the nucleus accumbens (NAcc) and prefrontal cortex after acute cocaine administration (20 mg kg(-1), intraperitoneal), whereas noradrenaline responses were preserved. Under cocaine, the attenuated DA and 5-HT activation in alpha CaMKIIT286A mice was followed by impaired c-Fos activation in the NAcc. To translate the rodent findings to human conditions, several CAMK2A gene polymorphisms were tested regarding their risk for a fast establishment of cocaine dependence in two independent samples of regular cocaine users from Brazil (n = 688) and Switzerland (n = 141). A meta-analysis across both samples confirmed that CAMK2A rs3776823 TT-allele carriers display a faster transition to severe cocaine use than C-allele carriers. Together, these data suggest that alpha CaMKII controls the speed for the establishment of cocaine's reinforcing effects. ; Institute of Psychiatry, King's College London ; Friedrich-Alexander-University of Erlangen-Nuremberg ; Medical Research Council, UK ; European Union ; FP7 project IMAGEMEND (IMAging GEnetics for MENtal Disorders) ; Innovative Medicine Initiative Project EU-AIMS ; Medical Research Council ; Swedish funding agency FORMAS ; Bundesministerium fur Bildung und Forschung (BMBF) ; Swiss National Science Foundation (SNSF) ; Olga Mayenfisch Foundation ; Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) ; Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) ; Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Res Ctr, MRC, London, England ; Univ Nottingham, Sch Med, Fac Med & Hlth Sci, Nottingham, England ; Univ Zurich, Hosp Psychiat, Dept Psychiat Psychotherapy & Psychosomat, Zurich, Switzerland ; Kings Coll London, Inst Psychiat, Ctr Cellular Basis Behav, London, England ; Univ Clin Erlangen, Dept Child & Adolescent Mental Hlth, Erlangen, Germany ; Islamic Azad Univ, Fac Sci, Dept Biol, Karaj Branch, Karaj, Iran ; Univ Penn, Sch Med, Dept Psychiat, Translat Res Lab, Philadelphia, PA 19104 USA ; Univ São Paulo, Sch Med, Dept & Inst Psychiat, São Paulo, Brazil ; Universidade Federal de São Paulo, UNIAD, São Paulo, Brazil ; Univ Bonn, Dept Psychiat, Bonn, Germany ; Univ Erlangen Nurnberg, Univ Hosp, Dept Psychiat & Psychotherapy, D-91054 Erlangen, Germany ; Universidade Federal de São Paulo, UNIAD, São Paulo, Brazil ; European Union: LSHM-CT-2007-037286 ; Innovative Medicine Initiative Project EU-AIMS: 115300-2 ; Medical Research Council: 93558 ; Bundesministerium fur Bildung und Forschung (BMBF): 01EV0711 ; Swiss National Science Foundation (SNSF): PP00P1-123516/1 ; Swiss National Science Foundation (SNSF): PP00P1-146326/1 ; Web of Science