M. Wampers

Risk of metabolic syndrome and its components in people with schizophrenia and related psychotic disorders, bipolar disorder and major depressive disorder: a systematic review and meta-analysis

Metabolic syndrome (MetS) and its components are highly predictive of cardiovascular diseases. The primary aim of this systematic review and meta‐analysis was to assess the prevalence of MetS and its components in people with schizophrenia and related psychotic disorders, bipolar disorder and major depressive disorder, comparing subjects with different disorders and taking into account demographic variables and psychotropic medication use. The secondary aim was to compare the MetS prevalence in persons with any of the selected disorders versus matched general population controls. The pooled MetS prevalence in people with severe mental illness was 32.6% (95% CI: 30.8%‐34.4%; N = 198; n = 52,678). Relative risk meta‐analyses established that there was no significant difference in MetS prevalence in studies directly comparing schizophrenia versus bipolar disorder, and in those directly comparing bipolar disorder versus major depressive disorder. Only two studies directly compared people with schizophrenia and major depressive disorder, precluding meta‐analytic calculations. Older age and a higher body mass index were significant moderators in the final demographic regression model (z = −3.6, p = 0.0003, r2 = 0.19). People treated with all individual antipsychotic medications had a significantly (p<0.001) higher MetS risk compared to antipsychotic‐naïve participants. MetS risk was significantly higher with clozapine and olanzapine (except vs. clozapine) than other antipsychotics, and significantly lower with aripiprazole than other antipsychotics (except vs. amisulpride). Compared with matched general population controls, people with severe mental illness had a significantly increased risk for MetS (RR = 1.58; 95% CI: 1.35‐1.86; p<0.001) and all its components, except for hypertension (p = 0.07). These data suggest that the risk for MetS is similarly elevated in the diagnostic subgroups of severe mental illness. Routine screening and multidisciplinary management of medical and behavioral conditions is needed in these patients. Risks of individual antipsychotics should be considered when making treatment choices.

TYPICAL AND ATYPICAL ANTIPSYCHOTICS DIFFERENTIALLY AFFECT LONG-TERM INCIDENCE RATES OF THE METABOLIC SYNDROME IN FIRST-EPISODE PATIENTS WITH SCHIZOPHRENIA: A RETROSPECTIVE CHART REVIEW

UNLABELLED The presence of the metabolic syndrome (MetS) is an important risk factor for cardiovascular disease and diabetes. There are limited data on the prevalence of MetS in patients with schizophrenia at the onset of the disorder and specifically no data on patients treated in the era when only first-generation antipsychotics were available. METHODS Data from a historic cohort of consecutively admitted first-episode patients with schizophrenia treated with first-generation antipsychotics (FGAs) were compared with an age and sex matched series of consecutive first-episode patients treated only with second-generation antipsychotics (SGAs). Rates of MetS were compared at baseline and after on average 3 years of treatment exposure. RESULTS At first episode there was no difference in the prevalence of MetS between the historic and the current cohort. Rates of MetS increased over time in both groups, but patients started on SGAs had a three times higher incidence rate of MetS (Odds Ratio 3.6, CI 1.7-7.5). The average increase in weight and body mass index was twice as high in patients started on SGA. The difference between the FGA and SGA group was no longer significant when patients started on clozapine and olanzapine were excluded. CONCLUSION Rates of MetS at the first episode of schizophrenia today are not different from those of patients 15 to 20 years ago. This finding counters the notion that the high rates of metabolic abnormalities in patients with schizophrenia currently reported are mainly due to lifestyle changes over time in the general population. Some SGAs have a significantly more negative impact on the incidence of MetS compared to FGAs in first-episode patients.

Prevalence of diabetes and the metabolic syndrome in a sample of patients with bipolar disorder

OBJECTIVES The presence of metabolic abnormalities is an important risk factor for cardiovascular disease and diabetes. There are limited data on the prevalence of the metabolic abnormalities in disorders other than schizophrenia in which antipsychotic medication is part of routine treatment. METHODS Sixty consecutive patients with bipolar disorder (BD) at our university psychiatric hospital and affiliate services were entered in an extensive prospective metabolic study including an oral glucose tolerance test. The prevalence of the metabolic syndrome was assessed based on the National Cholesterol Education Program Adult Treatment Protocol (ATP-III) criteria, the adapted ATP-III criteria using a fasting glucose threshold of 100 mg/dL, and the recently proposed criteria from the International Diabetes Federation (IDF). RESULTS The analysis of 60 patients showed a prevalence of the metabolic syndrome of 16.7% (ATP-III), 18.3% (adapted ATP-III) and 30.0% (IDF), respectively. A total of 6.7% of the patients met criteria for diabetes and 23.3% for pre-diabetic abnormalities. CONCLUSIONS The metabolic syndrome and glucose abnormalities are highly prevalent among patients with BD. They represent an important risk for cardiovascular and metabolic disorders. Assessment of the presence and monitoring of metabolic abnormalities and its associated risks should be part of the clinical management of patients with BD.

Prevalence of diabetes, metabolic syndrome and metabolic abnormalities in schizophrenia over the course of the illness: a cross-sectional study.

BackgroundPatients with schizophrenia are at high risk of developing metabolic abnormalities.MethodA prospective study focusing on metabolic disturbances in patients with schizophrenia, including an oral glucose tolerance test, is currently ongoing at our University Hospital and affiliate services. The prevalence of metabolic abnormalities at baseline was assessed in a cohort of 415 patients with schizophrenia. The sample was divided into 4 groups according to duration of illness: first-episode patients (<1.5 years), recent-onset patients (between 1.5 and 10 years), subchronic patients (between 10 and 20 years) and chronic patients (>20 years).ResultsMetabolic abnormalities were already present in first-episode patients, and considerably increased with increasing duration of illness. When compared to the general population matched for age and gender, much higher rates of the metabolic syndrome (MetS) and diabetes were observed for patients with schizophrenia. For MetS, the increase over time was similar to that of the general population. In contrast, the difference in the prevalence of diabetes in patients with schizophrenia and the general population dramatically and linearly increased from 1.6% in the 15–25 age-band to 19.2% in the 55–65 age-band.ConclusionThus, the current data suggest that on the one hand metabolic abnormalities are an inherent part of schizophrenic illness, as they are already present in first-episode patients. On the other hand, however, our results suggest a direct effect of the illness and/or antipsychotic medication on their occurence. The data underscore the need for screening for metabolic abnormalities in patients diagnosed with schizophrenia, already starting from the onset of the illness.

A meta-analysis of cardio-metabolic abnormalities in drug naïve, first-episode and multi-episode patients with schizophrenia versus general population controls

A meta‐analysis was conducted to explore the risk for cardio‐metabolic abnormalities in drug naïve, first‐episode and multi‐episode patients with schizophrenia and age‐ and gender‐ or cohort‐matched general population controls. Our literature search generated 203 relevant studies, of which 136 were included. The final dataset comprised 185,606 unique patients with schizophrenia, and 28 studies provided data for age‐ and gender‐matched or cohort‐matched general population controls (n=3,898,739). We found that multi‐episode patients with schizophrenia were at increased risk for abdominal obesity (OR=4.43; CI=2.52‐7.82; p<0.001), hypertension (OR=1.36; CI=1.21‐1.53; p<0.001), low high‐density lipoprotein cholesterol (OR=2.35; CI=1.78‐3.10; p<0.001), hypertriglyceridemia (OR=2.73; CI=1.95‐3.83; p<0.001), metabolic syndrome (OR=2.35; CI=1.68‐3.29; p<0.001), and diabetes (OR=1.99; CI=1.55‐2.54; p<0.001), compared to controls. Multi‐episode patients with schizophrenia were also at increased risk, compared to first‐episode (p<0.001) and drug‐naïve (p<0.001) patients, for the above abnormalities, with the exception of hypertension and diabetes. Our data provide further evidence supporting WPA recommendations on screening, follow‐up, health education and lifestyle changes in people with schizophrenia.

Neurocognition in clinical high risk young adults who did or did not convert to a first schizophrenic psychosis: A meta-analysis

BACKGROUND Individuals at clinical high risk (CHR) for psychosis have become a major focus for research designed to explore early predictors of transition to full psychosis. Characterizing differences in neurocognitive (NC) functioning between psychosis converters (CHR-C) and non-converters (CHR-NC) might contribute to the identification of specific NC predictors of psychosis onset. Therefore, the aim of the present meta-analysis was to compare the baseline NC performance between CHR-C and CHR-NC. METHOD PubMed (MEDLINE), Web of Science, Embase and reference lists were searched for studies reporting baseline cognitive data of CHR-C and CHR-NC. Included NC tests were classified within the MATRICS - Measurement and Treatment Research to Improve Cognition in Schizophrenia - cognitive domains. RESULTS Of 95 studies assessed for eligibility, 9 studies comprising 583 CHR subjects (N CHR-C=195, N CHR-NC=388) met all the inclusion criteria. CHR-C performed significantly worse compared to CHR-NC on 2 MATRICS domains namely working memory (ES=-0.29, 95% CI=-0.53 to -0.05) and visual learning (ES=-0.40, 95% CI=-0.68 to -0.13). For the remaining 4 domains (processing speed, attention/vigilance, verbal learning, reasoning/problem solving) no significant differences between CHR-C and CHR-NC were observed. CONCLUSION Based on the current meta-analytic data we might conclude that it is possible to differentiate between CHR-C and CHR-NC with respect to working memory and visual learning. The addition of visual learning and working memory tasks to psychosis regression models might contribute to the predictive power of these models.

Functional Division of the Visual Field: Moving Masks and Moving Windows

Publisher Summary The human eyes do not have the same resolution and sensitivity at every position of the retina. Fine details can only be discriminated efficiently by the fovea (the central part of the retina). At higher eccentricities, perceptual acuity decreases rapidly, and only coarse-grained information can be resolved. Consequently, peripheral vision is not particularly suited for object identification or word recognition, as these processes rely on detailed image analyses. Eye movements, or saccades, are required to project image areas onto the fovea. Saccades are not made to random image locations. Most fixations occur on interesting parts of the stimulus, such as words in a text or objects in a scene. Extrafoveal information can be used successfully to guide saccades to informative stimulus locations. By disentangling foveal and peripheral vision the concepts of moving mask and moving window are studied. Coarse peripheral information is preferred to obtain global image characteristics, while object localization gets benefited most from a high resolution peripheral image.Publisher Summary The human eyes do not have the same resolution and sensitivity at every position of the retina. Fine details can only be discriminated efficiently by the fovea (the central part of the retina). At higher eccentricities, perceptual acuity decreases rapidly, and only coarse-grained information can be resolved. Consequently, peripheral vision is not particularly suited for object identification or word recognition, as these processes rely on detailed image analyses. Eye movements, or saccades, are required to project image areas onto the fovea. Saccades are not made to random image locations. Most fixations occur on interesting parts of the stimulus, such as words in a text or objects in a scene. Extrafoveal information can be used successfully to guide saccades to informative stimulus locations. By disentangling foveal and peripheral vision the concepts of moving mask and moving window are studied. Coarse peripheral information is preferred to obtain global image characteristics, while object localization gets benefited most from a high resolution peripheral image.

Scene Exploration with Fourier-Filtered Peripheral Information:

In a previous moving-window study it was found that scene exploration benefits more from peripheral information of high spatial frequency than of low spatial frequency. In the present study, degraded versions of realistic scenes were presented peripherally during the initial 150 ms of fixations, while the undegraded scene was presented foveally. The undegraded version of the scene was visible both foveally and peripherally during the later part of fixations. During the initial 150 ms, the peripheral part of scenes was low-pass, bandpass, or high-pass filtered, blanked, or decreased in luminance. In a no-change condition, the undegraded scene was presented throughout the whole fixation. Participants freely explored the scenes in the context of an object-decision task. It was found that degrading peripheral information during the initial part of fixations had minimal effect on scene exploration. No reliable differences were found among the three filter types. The results indicate that, in the context of an object-search task, peripheral information is of minor importance during the initial part of fixations.

Markers of inflammation in schizophrenia: association vs. causation.

Inflammation is a complex response of the host to tissue injury, such as infection or physical insult 1. The main role of inflammation is to quickly eliminate pathogens by initiating an adaptive immune response through stimulation of antigen-specific T- and B-lymphocytes and their regulating immune-transmitters, the pro-inflammatory cytokines. Cytokines are divided into predominantly pro-inflammatory and predominantly anti-inflammatory types 2. Pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), are secreted by monocytes and macrophages and activate other cellular components of the inflammatory response. Anti-inflammatory cytokines, such as interleukin-4 (IL-4), help to down-regulate the inflammatory immune response. The role of inflammation in schizophrenia has received intense attention and a cytokine-mediated mechanism represents the keystone of a number of hypotheses formulated in the past two decades 2–4. The macrophage T-lymphocyte hypothesis postulates that chronically activated macrophages produce cytokines, such as interleukin-1 (IL-1), interleukin-2 (IL-2), tumor necrosis factors, interferon-alpha and interferon-gamma 5. The “T helper hypothesis” advances the idea of a shift away from cytotoxic cell immune function toward humoral immune reactivity 6. The microglia hypothesis argues that pro-inflammatory cytokines and free radicals are released by activated central nervous system microglia, causing abnormal neurogenesis, neural degradation and white matter abnormalities, which are known to play a role in the pathogenesis of schizophrenia 7. A convergence between neuroinflammatory changes and dopamine and glutamate receptors has also been postulated, and clinical trials with biological therapies developed for the reduction of inflammation 8,9 and for autoimmune disorders 10,11 are seriously considered. The significance of cytokine abnormalities and other markers of immune dysfunction identified in patients with schizophrenia can be examined through the prism of Bradford Hills guidelines 12, a widely accepted model for judging whether an association can contribute to cause a pathological phenomenon. Based on this framework, we evaluate here the strength of the association; its consistency in studies performed by different investigators on different samples; its temporality, by trying to determine whether the inflammation has preceded the onset of schizophrenia; its biological gradient, meaning that the severity of schizophrenia should correlate with the magnitude of the inflammatory process; its plausibility as a pathophysiological mechanism; the coherence between epidemiological and laboratory findings; and the specificity of inflammatory abnormalities.

Pharmacological treatment of ambulatory schizophrenic patients in Belgium

Backgroundthe objective of this study was twofold:1) Describe the use of antipsychotic treatments in ambulatory patients suffering from schizophrenia in Belgium.2) Evaluate to which extend antipsychotic treatment prescribing patterns are in accordance with published treatment guidelines.MethodA cross-sectional survey was carried out in 16 Belgian hospitals selected from a sample of 67 hospitals. The hospitals were equally distributed between the north and south part of the country and were representative of Belgian practice. During 2 months, participating psychiatrists were asked to record the medication use as well as demographic parameters of all consecutive ambulatory patients seen at their consultation or attending a day-hospital. Data concerning 1000 ambulatory patients with schizophrenia or schizoaffective disorder were collected.ResultsIn Belgium, the use of atypical antipsychotics is frequent (69%) in ambulatory patients with schizophrenia. In the overall sample, 73% receive only one antipsychotic drug. The majority of patients are treated with drugs of only one antipsychotic drug group, either first- typical (29.8%) or second-generation, atypical antipsychotics (53.2%). 15.8% of patients combine different types of antipsychotics. Antipsychotic dosing is adequate for the majority of patients but about one fifth receives a higher than recommended dose as per package inserts. Polypharmacy remains within reasonable limits. The use of concomitant medication varies according the antipsychotic treatment: patients who take second-generation antipsychotics only, receive the least additional drugs.ConclusionAtypical antipsychotics appear to be the first line treatment for schizophrenic psychosis. Psychiatrists working with ambulatory patients are well aware of treatment guidelines and follow them quite adequately.