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      Metabolic syndrome in psychiatric patients: overview, mechanisms, and implications Translated title: El síndrome metabólico en pacientes psiquiátricos: análisis, mecanismos y consecuencias Translated title: Analyse, mécanismes et implications du syndrome métabolique chez les patients psychiatriques

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          Abstract

          Psychiatric patients have a greater risk of premature mortality, predominantly due to cardiovascular diseases (CVDs). Convincing evidence shows that psychiatric conditions are characterized by an increased risk of metabolic syndrome (MetS), a clustering of cardiovascular risk factors including dyslipidemia, abdominal obesity, hypertension, and hyperglycemia. This increased risk is present for a range of psychiatric conditions, including major depressive disorder (MDD), bipolar disorder (BD), schizophrenia, anxiety disorder, attention-deficit/hyperactivity disorder (ADHD), and posttraumatic stress disorder (PTSD). There is some evidence for a dose-response association with the severity and duration of symptoms and for a bidirectional longitudinal impact between psychiatric disorders and MetS. Associations generally seem stronger with abdominal obesity and dyslipidemia dysregulations than with hypertension. Contributing mechanisms are an unhealthy lifestyle and a poor adherence to medical regimen, which are prevalent among psychiatric patients. Specific psychotropic medications have also shown a profound impact in increasing MetS dysregulations. Finally, pleiotropy in genetic vulnerability and pathophysiological mechanisms, such as those leading to the increased central and peripheral activation of immunometabolic or endocrine systems, plays a role in both MetS and psychiatric disorder development. The excess risk of MetS and its unfavorable somatic health consequences justifies a high priority for future research, prevention, close monitoring, and treatment to reduce MetS in the vulnerable psychiatric patient.

          Translated abstract

          Los pacientes psiquiátricos tienen un mayor riesgo de mortalidad prematura, principalmente por enfermedades cardiovasculares (ECVs). Existe evidencia convincente que muestra que las condiciones psiquiátricas están caracterizadas por un aumento del riesgo del síndrome metabólico (SMet), un conjunto de factores de riesgo cardiovascular que incluyen dislipidemia, obesidad abdominal, hipertensión e hiperglicemia. Este riesgo aumentado se presenta en diversas condiciones psiquiátricas como trastorno depresivo mayor (TDM), trastorno bipolar (TB), esquizofrenia, trastorno de ansiedad, trastorno por déficit de atención con hiperactividad (TDAH) y trastorno por estrés postraumático (TEPT). Al parecer existe alguna evidencia de una asociación dosis-respuesta entre la gravedad y duración de los síntomas y el impacto longitudinal bidireccional entre los trastornos psiquiátricos y el SMet. En general las asociaciones parecen más potentes con la obesidad abdominal y la dislipidemia que con la hipertensión. Los mecanismos que contribuyen a esto son un estilo de vida poco saludable y una pobre adherencia al tratamiento médico, condiciones que son prevalentes entre los pacientes psiquiátricos. Los medicamentos psicotrópicos específicos también han demostrado un impacto importante en el aumento de las fallas en la regulación del SMet. Por último, la pleiotropía en la vulnerabilidad genética y los mecanismos fisiopatológicos, como los que conducen a una mayor activación central y periférica de los sistemas inmunometabólico y endocrino, tienen un papel tanto en el desarrollo del SMet como del trastorno psiquiátrico. El riesgo aumentado del SMet y las consecuencias desfavorables en la salud somática justifican una prioridad alta para la investigación, prevención, monitorización estricta y tratamiento para reducir a futuro el SMet en el paciente psiquiátrico vulnerable.

          Translated abstract

          Les patients psychiatriques ont un risque plus élevé de mortalité prématurée, surtout en raison des maladies cardiovasculaires (MCV). D'après des données convaincantes, les troubles psychiatriques se caractérisent par un risque augmenté de syndrome métabolique (SM), un ensemble de facteurs de risque cardiovasculaire comprenant une dyslipidémie, une obésité abdominale, une hypertension et une hyperglycémie. Dans ces troubles psychiatriques, on trouve le trouble dépressif caractérisé (TDC), le trouble bipolaire (TB), la schizophrénie, le trouble anxieux, le trouble déficit de l'attention/hyperactivité (TDAH) et le trouble de stress post-traumatique (TSPT). Il semble exister une association dose-réponse entre la sévérité et la durée des symptômes et l'impact longitudinal bidirectionnel entre les troubles psychiatriques et le SM. Ces associations paraissent généralement plus fortes avec l'obésité abdominale et les dyslipidémies qu'avec l'hypertension. Un mode de vie malsain et une mauvaise adhésion au traitement médical, fréquents chez les patients psychiatriques, y participent. Les traitements psychotropes spécifiques influent fortement sur l'augmentation des dysrégulations du SM. Enfin, la pléiotropie de la vulnérabilité génétique et des mécanismes physiopathologiques, comme de ceux qui augmentent l'activation centrale et périphérique des systèmes endocriniens ou immunométaboliques, joue un rôle dans le développement à la fois du SM et des troubles psychiatriques. Ce risque majoré de SM et ses conséquences négatives sur la santé somatique justifient une priorité élevée pour la recherche, la prévention, la surveillance étroite et le traitement afin de diminuer dans l'avenir le SM chez les patients psychiatriques vulnérables.

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          The metabolic syndrome.

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            Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects: a systematic review and meta-analysis of randomized clinical trials.

            Several studies have reported antidepressant effects of anti-inflammatory treatment; however, the results have been conflicting and detrimental adverse effects may contraindicate the use of anti-inflammatory agents. To systematically review the antidepressant and possible adverse effects of anti-inflammatory interventions. Trials published prior to December, 31, 2013, were identified searching Cochrane Central Register of Controlled Trials, PubMed, EMBASE, PsychINFO, Clinicaltrials.gov, and relevant review articles. Randomized placebo-controlled trials assessing the efficacy and adverse effects of pharmacologic anti-inflammatory treatment in adults with depressive symptoms, including those who fulfilled the criteria for depression. Data were extracted by 2 independent reviewers. Pooled standard mean difference (SMD) and odds ratios (ORs) were calculated. Depression scores after treatment and adverse effects. Ten publications reporting on 14 trials (6262 participants) were included: 10 trials evaluated the use of nonsteroidal anti-inflammatory drugs (NSAIDs) (n=4,258) and 4 investigated cytokine inhibitors (n=2,004). The pooled effect estimate suggested that anti-inflammatory treatment reduced depressive symptoms (SMD, -0.34; 95% CI, -0.57 to -0.11; I2=90%) compared with placebo. This effect was observed in studies including patients with depression (SMD, -0.54; 95% CI, -1.08 to -0.01; I2=68%) and depressive symptoms (SMD, -0.27; 95% CI, -0.53 to -0.01; I2=68%). The heterogeneity of the studies was not explained by differences in inclusion of clinical depression vs depressive symptoms or use of NSAIDs vs cytokine inhibitors. Subanalyses emphasized the antidepressant properties of the selective cyclooxygenase 2 inhibitor celecoxib (SMD, -0.29; 95% CI, -0.49 to -0.08; I2=73%) on remission (OR, 7.89; 95% CI, 2.94 to 21.17; I2=0%) and response (OR, 6.59; 95% CI, 2.24 to 19.42; I2=0%). Among the 6 studies reporting on adverse effects, we found no evidence of an increased number of gastrointestinal or cardiovascular events after 6 weeks or infections after 12 weeks of anti-inflammatory treatment compared with placebo. All trials were associated with a high risk of bias owing to potentially compromised internal validity. Our analysis suggests that anti-inflammatory treatment, in particular celecoxib, decreases depressive symptoms without increased risks of adverse effects. However, a high risk of bias and high heterogeneity made the mean estimate uncertain. This study supports a proof-of-concept concerning the use of anti-inflammatory treatment in depression. Identification of subgroups that could benefit from such treatment might be warranted.
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              The effect of antidepressant medication treatment on serum levels of inflammatory cytokines: a meta-analysis.

              Serum levels of inflammatory cytokines, for example, tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and IL-1 beta (IL-1β), are elevated in subjects with major depressive disorder (MDD). The reason why this occurs is unclear. Elevated levels of inflammatory cytokines could be a result of brain dysfunction in MDD. It is also possible that inflammatory cytokines contribute to depressive symptoms in MDD. If the first assumption is correct, one would expect levels to normalize with resolution of the depressive episode after treatment. Several studies have measured changes in cytokine levels during antidepressant treatment; however, the results vary. The purpose of this study was to pool all available data on changes in serum levels of TNFα, IL-6, and IL-1β during antidepressant treatment to determine whether these levels change. Studies were included if they used an approved pharmacological treatment for depression, patients had a diagnosis of MDD, and serum levels of TNFα, IL-6, and/or IL-1β were measured before and after treatment. Twenty-two studies fulfilled these criteria. Meta-analysis of these studies showed that, overall, while pharmacological antidepressant treatment reduced depressive symptoms, it did not reduce serum levels of TNFα. On the other hand, antidepressant treatment did reduce levels of IL-1β and possibly those of IL-6. Stratified subgroup analysis by class of antidepressant indicated that serotonin reuptake inhibitors may reduce levels of IL-6 and TNFα. Other antidepressants, while efficacious for depressive symptoms, did not appear to reduce cytokine levels. These results argue against the notion that resolution of a depressive episode is associated with normalization of levels of circulating inflammatory cytokines; however, the results are consistent with the possibility that inflammatory cytokines contribute to depressive symptoms and that antidepressants block the effects of inflammatory cytokines on the brain.
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                Author and article information

                Contributors
                Journal
                Dialogues Clin Neurosci
                Dialogues Clin Neurosci
                Dialogues Clin Neurosci
                Dialogues in Clinical Neuroscience
                Les Laboratoires Servier (France )
                1294-8322
                1958-5969
                March 2018
                March 2018
                : 20
                : 1
                : 63-73
                Affiliations
                Department of Psychiatry, VU University Medical Center & GGZ InGeest, Amsterdam, The Netherlands
                Department of Psychiatry, VU University Medical Center & GGZ InGeest, Amsterdam, The Netherlands
                Author notes
                Article
                10.31887/DCNS.2018.20.1/bpenninx
                6016046
                29946213
                5aad8c48-7cf7-482d-8817-8fedc25966cd
                Copyright © 2018 AICH - Servier Research Group. All rights reserved

                This is an open-access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by-nc-nd/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Clinical Research

                Neurosciences
                abdominal obesity,bipolar disorder,cardiovascular disease,depression,dyslipidemia,metabolic syndrome,review,schizophrenia

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