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      The cross-sectional GRAS sample: A comprehensive phenotypical data collection of schizophrenic patients

      1 , 1 , 1 , 1 , 1 , 30 , 1 , 1 , 1 , 1 , 1 , 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 30 , 26 , 30 , 31 , 27 , 30 , 31 , 25 , 30 , 31 , 28 , 30 , 31 , 29 , 30 , 31 , , 1 , 30 , 31

      BMC Psychiatry

      BioMed Central

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          Abstract

          Background

          Schizophrenia is the collective term for an exclusively clinically diagnosed, heterogeneous group of mental disorders with still obscure biological roots. Based on the assumption that valuable information about relevant genetic and environmental disease mechanisms can be obtained by association studies on patient cohorts of ≥ 1000 patients, if performed on detailed clinical datasets and quantifiable biological readouts, we generated a new schizophrenia data base, the GRAS (Göttingen Research Association for Schizophrenia) data collection. GRAS is the necessary ground to study genetic causes of the schizophrenic phenotype in a 'phenotype-based genetic association study' (PGAS). This approach is different from and complementary to the genome-wide association studies (GWAS) on schizophrenia.

          Methods

          For this purpose, 1085 patients were recruited between 2005 and 2010 by an invariable team of traveling investigators in a cross-sectional field study that comprised 23 German psychiatric hospitals. Additionally, chart records and discharge letters of all patients were collected.

          Results

          The corresponding dataset extracted and presented in form of an overview here, comprises biographic information, disease history, medication including side effects, and results of comprehensive cross-sectional psychopathological, neuropsychological, and neurological examinations. With >3000 data points per schizophrenic subject, this data base of living patients, who are also accessible for follow-up studies, provides a wide-ranging and standardized phenotype characterization of as yet unprecedented detail.

          Conclusions

          The GRAS data base will serve as prerequisite for PGAS, a novel approach to better understanding 'the schizophrenias' through exploring the contribution of genetic variation to the schizophrenic phenotypes.

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          Most cited references 49

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          The positive and negative syndrome scale (PANSS) for schizophrenia.

          The variable results of positive-negative research with schizophrenics underscore the importance of well-characterized, standardized measurement techniques. We report on the development and initial standardization of the Positive and Negative Syndrome Scale (PANSS) for typological and dimensional assessment. Based on two established psychiatric rating systems, the 30-item PANSS was conceived as an operationalized, drug-sensitive instrument that provides balanced representation of positive and negative symptoms and gauges their relationship to one another and to global psychopathology. It thus constitutes four scales measuring positive and negative syndromes, their differential, and general severity of illness. Study of 101 schizophrenics found the four scales to be normally distributed and supported their reliability and stability. Positive and negative scores were inversely correlated once their common association with general psychopathology was extracted, suggesting that they represent mutually exclusive constructs. Review of five studies involving the PANSS provided evidence of its criterion-related validity with antecedent, genealogical, and concurrent measures, its predictive validity, its drug sensitivity, and its utility for both typological and dimensional assessment.
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            Schizophrenia: a concise overview of incidence, prevalence, and mortality.

            Recent systematic reviews have encouraged the psychiatric research community to reevaluate the contours of schizophrenia epidemiology. This paper provides a concise overview of three related systematic reviews on the incidence, prevalence, and mortality associated with schizophrenia. The reviews shared key methodological features regarding search strategies, analysis of the distribution of the frequency estimates, and exploration of the influence of key variables (sex, migrant status, urbanicity, secular trend, economic status, and latitude). Contrary to previous interpretations, the incidence of schizophrenia shows prominent variation between sites. The median incidence of schizophrenia was 15.2/100,000 persons, and the central 80% of estimates varied over a fivefold range (7.7-43.0/100,000). The rate ratio for males:females was 1.4:1. Prevalence estimates also show prominent variation. The median lifetime morbid risk for schizophrenia was 7.2/1,000 persons. On the basis of the standardized mortality ratio, people with schizophrenia have a two- to threefold increased risk of dying (median standardized mortality ratio = 2.6 for all-cause mortality), and this differential gap in mortality has increased over recent decades. Compared with native-born individuals, migrants have an increased incidence and prevalence of schizophrenia. Exposures related to urbanicity, economic status, and latitude are also associated with various frequency measures. In conclusion, the epidemiology of schizophrenia is characterized by prominent variability and gradients that can help guide future research.
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              Multiple choice vocabulary test MWT as a valid and short test to estimate premorbid intelligence.

              The discrepancy between current and premorbid ability is a relevant indicator of acquired mental impairment, which itself is closely related to general cerebral dysfunction. The use of tests sensitive to cerebral dysfunction, raises relatively few problems compared with tests being resistant that are used to estimate premorbid mental ability. For premorbid ability, verbal tests assessing knowledge, especially vocabulary, have been shown to be valid. A test, possibly more insensitive to brain dysfunction than the ones usually administered, is the multiple choice vocabulary test (MWT = Mehrfachwahl-Wortschatz-Test). At present only German versions are available. They are presented in some detail because of their advantages. Construction of the MWT is simple, and it can be easily administered in about five minutes. The results correlate fairly well with global IQ in healthy adults (median of r = 0.72 in 22 samples) and are more insensitive to current disturbances than such tests as the WAIS vocabulary test. The limitations of premorbid tests with respect to diagnostic validity are discussed. It is concluded, that studies which do not control premorbid intelligence have to be considered as a "malpractice" and should not be accepted by scientists.
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                Author and article information

                Journal
                BMC Psychiatry
                BMC Psychiatry
                BioMed Central
                1471-244X
                2010
                10 November 2010
                : 10
                : 91
                Affiliations
                [1 ]Division of Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany
                [2 ]Department of Psychiatry and Psychotherapy, Ecumenical Hospital Hainich, Germany
                [3 ]Hospital of Psychiatry and Psychotherapy, Center for Integrative Psychiatry, Kiel, Germany
                [4 ]Karl-Jaspers-Hospital, Psychiatric Federation Oldenburger Land, Bad Zwischenahn, Germany
                [5 ]Department of Psychiatry II, Ulm University, District Hospital Günzburg, Germany
                [6 ]Department of Psychiatry and Psychotherapy, Hospital Fulda, Germany
                [7 ]Department of Psychiatry and Psychotherapy, Isar-Amper-Hospital, Taufkirchen (Vils), Germany
                [8 ]Department of Psychiatry and Psychotherapy, Reinhard-Nieter Hospital, Wilhelmshaven, Germany
                [9 ]Vitos Hospital of Forensic Psychiatry Eltville, Eltville, Germany
                [10 ]Vitos Hospital of Psychiatry and Psychotherapy Merxhausen, Kassel, Germany
                [11 ]Department of Psychiatry and Psychotherapy, University of Rostock, Germany
                [12 ]Hospital of Forensic Psychiatry, Moringen, Germany
                [13 ]Hospital of Psychiatry and Psychotherapy Langenhagen, Regional Hospitals Hannover, Germany
                [14 ]Vitos Hospital of Psychiatry and Psychotherapy, Bad Emstal-Merxhausen, Germany
                [15 ]Addiction Hospital "Am Waldsee", Rieden, Germany
                [16 ]Department of Psychiatry and Psychotherapy, University Medical Center of Bonn, Germany
                [17 ]Vitos Hospital of Psychiatry and Psychotherapy Merxhausen, Hofgeismar, Germany
                [18 ]Vitos Haina Forensic Psychiatric Hospital, Haina, Germany
                [19 ]Department of Psychiatry and Psychotherapy, Regional Hospitals Hannover, Wunstorf, Germany
                [20 ]Dr. K. Fontheim's Hospital for Mental Health, Liebenburg, Germany
                [21 ]Department of Psychiatry and Psychotherapy, Hospital Ingolstadt, Germany
                [22 ]Department of Psychiatry and Psychotherapy, Hospital Lübbecke, Germany
                [23 ]Hospital of Psychiatry and Psychotherapy, Rickling, Germany
                [24 ]Georg-Elias-Müller-Institute for Psychology, University of Göttingen, Germany
                [25 ]Department of Psychiatry and Psychotherapy, University Medical Center of Göttingen, Germany
                [26 ]Biomedical NMR Research GmbH, Max Planck Institute of Biophysical Chemistry, Göttingen, Germany
                [27 ]Department of Molecular Biology of Neuronal Signals, Max Planck Institute of Experimental Medicine, Göttingen, Germany
                [28 ]Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Göttingen, Germany
                [29 ]Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, Germany
                [30 ]DFG Research Center for Molecular Physiology of the Brain (CMPB), Germany
                [31 ]Founders of the GRAS Initiative
                Article
                1471-244X-10-91
                10.1186/1471-244X-10-91
                3002316
                21067598
                Copyright ©2010 Ribbe et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<url>http://creativecommons.org/licenses/by/2.0</url>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Categories
                Research Article

                Clinical Psychology & Psychiatry

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