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      Increased Mortality in Schizophrenia Due to Cardiovascular Disease – A Non-Systematic Review of Epidemiology, Possible Causes, and Interventions

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          Abstract

          Background: Schizophrenia is among the major causes of disability worldwide and the mortality from cardiovascular disease (CVD) is significantly elevated. There is a growing concern that this health challenge is not fully understood and efficiently addressed.

          Methods: Non-systematic review using searches in PubMed on relevant topics as well as selection of references based on the authors’ experience from clinical work and research in the field.

          Results: In most countries, the standardized mortality rate in schizophrenia is about 2.5, leading to a reduction in life expectancy between 15 and 20 years. A major contributor of the increased mortality is due to CVD, with CVD mortality ranging from 40 to 50% in most studies. Important causal factors are related to lifestyle, including poor diet, lack of physical activity, smoking, and substance abuse. Recent findings suggest that there are overlapping pathophysiology and genetics between schizophrenia and CVD-risk factors, further increasing the liability to CVD in schizophrenia. Many pharmacological agents used for treating psychotic disorders have side effects augmenting CVD risk. Although several CVD-risk factors can be effectively prevented and treated, the provision of somatic health services to people with schizophrenia seems inadequate. Further, there is a sparseness of studies investigating the effects of lifestyle interventions in schizophrenia, and there is little knowledge about effective programs targeting physical health in this population.

          Discussion: The risk for CVD and CVD-related deaths in people with schizophrenia is increased, but the underlying mechanisms are not fully known. Coordinated interventions in different health care settings could probably reduce the risk. There is an urgent need to develop and implement effective programs to increase life expectancy in schizophrenia, and we argue that mental health workers should be more involved in this important task.

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          Most cited references146

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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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            Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects.

            Schizophrenia is associated with immune system dysfunction, including aberrant cytokine levels. We performed a meta-analysis of these associations, considering effects of clinical status and antipsychotic treatment following an acute illness exacerbation. We identified articles by searching PubMed, PsychInfo, and Institute for Scientific Information and the reference lists of identified studies. Forty studies met the inclusion criteria. Effect sizes were similar for studies of acutely relapsed inpatients (AR) and first-episode psychosis (FEP). Interleukin (IL)-1β, IL-6, and transforming growth factor-β (TGF-β) appeared to be state markers, as they were increased in AR and FEP (p < .001 for each) and normalized with antipsychotic treatment (p < .001, p = .008, and p = .005, respectively). In contrast, IL-12, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and soluble IL-2 receptor (sIL-2R) appeared to be trait markers, as levels remained elevated in acute exacerbations and following antipsychotic treatment. There was no difference in IL-6 levels between stable medicated outpatients and control subjects (p = .69). In the cerebrospinal fluid, IL-1β was significantly decreased in schizophrenia versus controls (p = .01). Similar effect sizes in AR and FEP suggest that the association between cytokine abnormalities and acute exacerbations of schizophrenia is independent of antipsychotic medications. While some cytokines (IL-1β, IL-6, and TGF-β) may be state markers for acute exacerbations, others (IL-12, IFN-γ, TNF-α, and sIL-2R) may be trait markers. Although these results could provide the basis for future hypothesis testing, most studies did not control for potential confounding factors such as body mass index and smoking. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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              What are the functional consequences of neurocognitive deficits in schizophrenia?

              M. Green (1996)
              It has been well established that schizophrenic patients have neurocognitive deficits, but it is not known how these deficits influence the daily lives of patients. The goal of this review was to determine which, if any, neurocognitive deficits restrict the functioning of schizophrenic patients in the outside world. The author reviewed studies that have evaluated neurocognitive measures as predictors and correlates of functional outcome for schizophrenic patients. The review included 1) studies that have prospectively evaluated specific aspects of neurocognition and community (e.g., social and vocational) functioning (six studies), 2) all known studies of neurocognitive correlates of social problem solving (five studies), and 3) all known studies of neurocognitive correlates and predictors of psychosocial skill acquisition (six studies). Despite wide variation among studies in the selection of neurocognitive measures, some consistencies emerged. The most consistent finding was that verbal memory was associated with all types of functional outcome. Vigilance was related to social problem solving and skill acquisition. Card sorting predicted community functioning but not social problem solving. Negative symptoms were associated with social problem solving but not skill acquisition. Notably, psychotic symptoms were not significantly associated with outcome measures in any of the studies reviewed. Verbal memory and vigilance appear to be necessary for adequate functional outcome. Deficiencies in these areas may prevent patients from attaining optimal adaptation and hence act as "neurocognitive rate-limiting factors." On the basis of this review of the literature, a series of hypotheses are offered for follow-up studies.
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                Author and article information

                Contributors
                URI : http://frontiersin.org/people/u/129150
                URI : http://frontiersin.org/people/u/160064
                URI : http://frontiersin.org/people/u/158558
                URI : http://frontiersin.org/people/u/184427
                URI : http://frontiersin.org/people/u/552
                Journal
                Front Psychiatry
                Front Psychiatry
                Front. Psychiatry
                Frontiers in Psychiatry
                Frontiers Media S.A.
                1664-0640
                26 September 2014
                2014
                : 5
                : 137
                Affiliations
                [1] 1NORMENT, KG Jebsen Centre for Psychosis Research, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo , Oslo, Norway
                [2] 2Division of Mental Health and Addiction, Oslo University Hospital , Oslo, Norway
                [3] 3Division of Mental Health and Addiction, Vestfold Hospital Trust , Tønsberg, Norway
                Author notes

                Edited by: Jørn Heggelund, Trondheim University Hospital, Norway

                Reviewed by: Lars Lien, National Center for Dual Diagnosis, Norway; Steve Brown, Southern Health Foundation, UK

                *Correspondence: Ole A. Andreassen, Oslo universitetssykehus HF, Klinikk psykisk hele og avhengighet, Sekjson for psykoseforskning/TOP, Ullevål sykehus, bygg 49, Postboks 4956 Nydalen, 0424 Oslo, Norway e-mail: o.a.andreassen@ 123456medisin.uio.no

                This article was submitted to Schizophrenia, a section of the journal Frontiers in Psychiatry.

                Article
                10.3389/fpsyt.2014.00137
                4175996
                25309466
                29a58307-019e-4629-adb3-0aeca0166602
                Copyright © 2014 Ringen, Engh, Birkenaes, Dieset and Andreassen.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 13 April 2014
                : 12 September 2014
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 193, Pages: 11, Words: 11473
                Categories
                Psychiatry
                Review Article

                Clinical Psychology & Psychiatry
                schizophrenia,mortality,metabolic syndrome x,physical training,lifestyle,cardiovascular diseases

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