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      Evidence for a Shared Etiological Mechanism of Psychotic Symptoms and Obsessive-Compulsive Symptoms in Patients with Psychotic Disorders and Their Siblings

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      1 , 2 , * , 3 , 4 , 2 , 5 , Genetic Risk and Outcome of Psychosis (GROUP) investigators
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          Abstract

          The prevalence of obsessive-compulsive disorder in subjects with psychotic disorder is much higher than in the general population. The higher than chance co-occurrence has also been demonstrated at the level of subclinical expression of both phenotypes. Both extended phenotypes have been shown to cluster in families. However, little is known about the origins of their elevated co-occurrence. In the present study, evidence for a shared etiological mechanism was investigated in 3 samples with decreasing levels of familial psychosis liability: 987 patients, 973 of their unaffected siblings and 566 healthy controls. The association between the obsessive-compulsive phenotype and the psychosis phenotype c.q. psychosis liability was investigated. First, the association was assessed between (subclinical) obsessive-compulsive symptoms and psychosis liability. Second, in a cross-sib cross-trait analysis, it was examined whether (subclinical) obsessive-compulsive symptoms in the patient were associated with (subclinical) psychotic symptoms in the related unaffected sibling. Evidence was found for both associations, which is compatible with a partially shared etiological pathway underlying obsessive-compulsive and psychotic disorder. This is the first study that used a cross-sib cross-trait design in patients and unaffected siblings, thus circumventing confounding by disease-related factors present in clinical samples.

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          Most cited references44

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          Construct validity in psychological tests.

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            SCAN. Schedules for Clinical Assessment in Neuropsychiatry.

            After more than 12 years of development, the ninth edition of the Present State Examination (PSE-9) was published, together with associated instruments and computer algorithm, in 1974. The system has now been expanded, in the framework of the World Health Organization/Alcohol, Drug Abuse, and Mental Health Administration Joint Project on Standardization of Diagnosis and Classification, and is being tested with the aim of developing a comprehensive procedure for clinical examination that is also capable of generating many of the categories of the International Classification of Diseases, 10th edition, and the Diagnostic and Statistical Manual of Mental Disorders, revised third edition. The new system is known as SCAN (Schedules for Clinical Assessment in Neuropsychiatry). It includes the 10th edition of the PSE as one of its core schedules, preliminary tests of which have suggested that reliability is similar to that of PSE-9. SCAN is being field tested in 20 centers in 11 countries. A final version is expected to be available in January 1990.
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              Psychiatric comorbidities and schizophrenia.

              Psychiatric comorbidities are common among patients with schizophrenia. Substance abuse comorbidity predominates. Anxiety and depressive symptoms are also very common throughout the course of illness, with an estimated prevalence of 15% for panic disorder, 29% for posttraumatic stress disorder, and 23% for obsessive-compulsive disorder. It is estimated that comorbid depression occurs in 50% of patients, and perhaps (conservatively) 47% of patients also have a lifetime diagnosis of comorbid substance abuse. This article chronicles these associations, examining whether these comorbidities are "more than chance" and might represent (distinct) phenotypes of schizophrenia. Among the anxiety disorders, the evidence at present is most abundant for an association with obsessive-compulsive disorder. Additional studies in newly diagnosed antipsychotic-naive patients and their first-degree relatives and searches for genetic and environmental risk factors are needed to replicate preliminary findings and further investigate these associations.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                10 June 2015
                2015
                : 10
                : 6
                : e0125103
                Affiliations
                [1 ]Arkin Mental Health and Addiction Treatment Centre, Amsterdam, the Netherlands
                [2 ]Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, Maastricht, the Netherlands
                [3 ]Department of psychiatry, Erasmus University Medical Center, Erasmus University, Rotterdam, the Netherlands
                [4 ]Department of psychiatry, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands
                [5 ]Academic Medical Centre University of Amsterdam, Department of Psychiatry, Amsterdam, The Netherlands
                UTHSCSH, UNITED STATES
                Author notes

                Competing Interests: Jansen-Cilag, Eli Lilly and Company, Astra-Zeneca and Lundbeck provided unrestricted grants for analysis. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: FVD MS RS IG LDH. Performed the experiments: IG LDH. Analyzed the data: FVD MS SR IG LDH. Wrote the paper: FVD MS RS IG LDH.

                ¶ Membership of the Genetic Risk and Outcome of Psychosis (GROUP) Investigators is provided in the Acknowledgments.

                Article
                PONE-D-15-04569
                10.1371/journal.pone.0125103
                4465647
                26061170
                f4cd228f-c990-40dd-aba4-e00f747f3a6d
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 6 February 2015
                : 5 May 2015
                Page count
                Figures: 2, Tables: 4, Pages: 15
                Funding
                This work was supported by the Geestkracht program of the Dutch Health Research Council (ZON-MW, grant number 10-000-1002) and matching funds from participating universities and mental health care organizations (Site Amsterdam: Academic Psychiatric Centre AMC, Ingeest, Arkin, Dijk en Duin, Rivierduinen, Erasmus MC, GGZ Noord Holland Noord; Site Utrecht: University Medical Centre Utrecht, Altrecht, Symfora, Meerkanten, Riagg Amersfoort, Delta; Site Groningen: University Medical Centre Groningen, Lentis, GGZ Friesland,GGZ Drenthe, Dimence, Mediant, GGZ De Grote Rivieren and Parnassia psycho-medical centre; Site Maastricht: Maastricht University Medical Centre, GGZ Eindhoven, GGZ Midden-Brabant, GGZ Oost-Brabant, GGZ Noord- Midden Limburg, Mondriaan Zorggroep, Prins Clauscentrum Sittard, RIAGG Roermond, Universitair Centrum Sint-Jozef Kortenberg, CAPRI University of Antwerp, PC Ziekeren Sint-Truiden, PZ Sancta Maria Sint-Truiden, GGZ Overpelt, OPZ Rekem). The analyses were supported by unrestricted grants from Jansen-Cilag, Eli Lilly and Company, Astra-Zeneca and Lundbeck. The research leading to these results has received funding from the European Community's Seventh Framework Program under grant agreement No. HEALTH-F2-2009-241909 (Project EU-GEI). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Custom metadata
                Due to ethical restrictions related to approved study protocols and participant consent, all relevant data are available upon request by contacting Lieuwe de Haan ( l.dehaan@ 123456amc.uva.nl ) and Inez Myin-Germeys ( i.germeys@ 123456maastrichtuniversity.nl ).

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