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      Patterns of schizophrenia symptoms: hidden structure in the PANSS questionnaire

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          Abstract

          The clinical presentation of patients with schizophrenia has long been described to be very heterogeneous. Coherent symptom profiles can probably be directly derived from behavioral manifestations quantified in medical questionnaires. The combination of machine learning algorithms and an international multi-site dataset ( n = 218 patients) identified distinctive patterns underlying schizophrenia from the widespread PANSS questionnaire. Our clustering approach revealed a negative symptom patient group as well as a moderate and a severe group, giving further support for the existence of schizophrenia subtypes. Additionally, emerging regression analyses uncovered the most clinically predictive questionnaire items. Small subsets of PANSS items showed convincing forecasting performance in single patients. These item subsets encompassed the entire symptom spectrum confirming that the different facets of schizophrenia can be shown to enable improved clinical diagnosis and medical action in patients. Finally, we did not find evidence for complicated relationships among the PANSS items in our sample. Our collective results suggest that identifying best treatment for a given individual may be grounded in subtle item combinations that transcend the long-trusted positive, negative, and cognitive categories.

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          Most cited references36

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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 genes, gene expression, and neuropathology: on the matter of their convergence.

            This review critically summarizes the neuropathology and genetics of schizophrenia, the relationship between them, and speculates on their functional convergence. The morphological correlates of schizophrenia are subtle, and range from a slight reduction in brain size to localized alterations in the morphology and molecular composition of specific neuronal, synaptic, and glial populations in the hippocampus, dorsolateral prefrontal cortex, and dorsal thalamus. These findings have fostered the view of schizophrenia as a disorder of connectivity and of the synapse. Although attractive, such concepts are vague, and differentiating primary events from epiphenomena has been difficult. A way forward is provided by the recent identification of several putative susceptibility genes (including neuregulin, dysbindin, COMT, DISC1, RGS4, GRM3, and G72). We discuss the evidence for these and other genes, along with what is known of their expression profiles and biological roles in brain and how these may be altered in schizophrenia. The evidence for several of the genes is now strong. However, for none, with the likely exception of COMT, has a causative allele or the mechanism by which it predisposes to schizophrenia been identified. Nevertheless, we speculate that the genes may all converge functionally upon schizophrenia risk via an influence upon synaptic plasticity and the development and stabilization of cortical microcircuitry. NMDA receptor-mediated glutamate transmission may be especially implicated, though there are also direct and indirect links to dopamine and GABA signalling. Hence, there is a correspondence between the putative roles of the genes at the molecular and synaptic levels and the existing understanding of the disorder at the neural systems level. Characterization of a core molecular pathway and a 'genetic cytoarchitecture' would be a profound advance in understanding schizophrenia, and may have equally significant therapeutic implications.
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              Searching for a consensus five-factor model of the Positive and Negative Syndrome Scale for schizophrenia.

              Although the developers of the Positive and Negative Syndrome Scale (PANSS) grouped items into three subscales, factor analyses indicate that a five-factor model better characterizes PANSS data. However, lack of consensus on which model to use limits the comparability of PANSS variables across studies. We counted "votes" from published factor analyses to derive consensus models. One of these combined superior fit in our Caucasian sample (n=458, CFI=.970), and in distinct Japanese sample (n=164, CFI=.964), relative to the original three-subscale model, with a sorting of items into factors that was highly consistent across the studies reviewed. Published by Elsevier B.V.
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                Author and article information

                Contributors
                danilo.bzdok@rwth-aachen.de
                Journal
                Transl Psychiatry
                Transl Psychiatry
                Translational Psychiatry
                Nature Publishing Group UK (London )
                2158-3188
                30 October 2018
                30 October 2018
                2018
                : 8
                : 237
                Affiliations
                [1 ]ISNI 0000 0001 0728 696X, GRID grid.1957.a, Department of Psychiatry, Psychotherapy, and Psychosomatics, , RWTH Aachen University, ; Aachen, Germany
                [2 ]Jülich Aachen Research Alliance (JARA) — Translational Brain Medicine, Aachen, Germany
                [3 ]ISNI 0000 0001 2186 3954, GRID grid.5328.c, Parietal Team, INRIA, ; Gif-sur-Yvette, France
                [4 ]ISNI 0000 0001 2190 1447, GRID grid.10392.39, Department of Psychiatry and Psychotherapy, , University of Tübingen, ; Tübingen, Germany
                [5 ]ISNI 0000 0001 2190 4373, GRID grid.7700.0, Department of Psychiatry, , University of Heidelberg, ; Heidelberg, Germany
                [6 ]BCN Neuroimaging Center, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
                [7 ]Univ Lille, CNRS UMR9193, SCALab & CHU Lille, Fontan Hospital, CURE platform, 59000 Lille, France
                [8 ]ISNI 0000000090126352, GRID grid.7692.a, UMC Utrecht Brain Center Rudolf Magnus, ; Utrecht, The Netherlands
                Author information
                http://orcid.org/0000-0002-8033-4953
                Article
                294
                10.1038/s41398-018-0294-4
                6207565
                30375374
                63b863c2-e3a8-4724-a0fb-19f7e6e0d8b0
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 20 July 2018
                : 12 September 2018
                : 5 October 2018
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                © The Author(s) 2018

                Clinical Psychology & Psychiatry
                Clinical Psychology & Psychiatry

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