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

ABSTRACT: Schizophrenia is associated with immune system dysfunction, including abnormal blood immune cell parameters. We performed a meta-analysis of these associations, considering the effect of clinical status and antipsychotic treatment following an acute exacerbation of psychosis.We identified articles by searching PubMed, PsycINFO, and Thomson Reuters (formerly ISI) Web of Knowledge and the reference lists of identified studies.Sixteen studies of blood lymphocytes met the inclusion criteria. There was insufficient data for a meta-analysis of the mononuclear phagocytic system. In cross-sectional studies, there was a significant increase in the CD4% and CD56% in acutely relapsed inpatients. Absolute levels of total lymphocytes, CD3, and CD4, and the CD4/CD8 ratio were significantly increased, and the CD3% was significantly decreased in drug-native first-episode psychosis. In longitudinal studies, the CD4/CD8 ratio appeared to be state-related markers, as it decreased following antipsychotic treatment for acute exacerbations of psychosis. Absolute CD56 levels appeared to be a trait marker, as levels significantly increased following antipsychotic treatment for relapse.Blood lymphocyte abnormalities in drug-naïve first-episode psychosis suggest an effect that may be independent of antipsychotic medications. While some parameters (CD4/CD8) may be state markers for acute exacerbations of psychosis, others (CD56) may be trait markers; however, more longitudinal studies are needed. Although these findings could provide the basis for future hypothesis testing, a relatively small number of studies and subjects, lack of correlative data with clinical features, and inadequate consideration of potential confounding factors limit the results.

SUBMITTER: Miller BJ

PROVIDER: S-EPMC3816144 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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

Miller Brian J BJ Gassama Bintou B Sebastian Dale D Buckley Peter P Mellor Andrew A

Biological psychiatry 20121011 10

<h4>Background</h4>Schizophrenia is associated with immune system dysfunction, including abnormal blood immune cell parameters. We performed a meta-analysis of these associations, considering the effect of clinical status and antipsychotic treatment following an acute exacerbation of psychosis.<h4>Methods</h4>We identified articles by searching PubMed, PsycINFO, and Thomson Reuters (formerly ISI) Web of Knowledge and the reference lists of identified studies.<h4>Results</h4>Sixteen studies of bl ...[more]

PMID: 23062357

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Project description:ImportanceBecause increasing placebo response rates decrease drug-placebo differences and increase the number of failed trials, it is imperative to determine what is causing this trend.ObjectivesTo investigate the relationship between antipsychotic medication and placebo response by publication year, and to identify associated study design and implementation variables.Data sourcesMEDLINE, PsycINFO, and PubMed were searched to identify randomized clinical trials of antipsychotic medications published from 1960 to July 2013.Study selectionIncluded were randomized clinical trials lasting 4 to 24 weeks, contrasting antipsychotic medication with placebo or an active comparator, and enrolling patients 18 years of age or older with schizophrenia or schizoaffective disorder.Data extraction and synthesisStandardized mean change scores were calculated for each treatment arm, plotted against publication year, and tested with Spearman rank correlation coefficients. Hierarchical linear modeling identified factors associated with the standardized mean change across medication and placebo treatment arms.Main outcomes and measuresWe hypothesized that the mean change in placebo-treated patients would significantly increase from 1960 to the present, that a greater change would be observed in active comparator vs placebo-controlled trials, and that more protocol visits would increase the symptom change observed.ResultsIn the 105 trials examined, the mean change observed in placebo arms increased significantly with year of publication (n=39, r=0.52, P=.001), while the mean change in effective dose medication arms decreased significantly (n=208, r=-0.26, P<.001). Significant interactions were found between assignment to effective dose medication and publication year (t260=-5.55, P<.001), baseline severity (t260=5.08, P<.001), and study duration (t260=-3.76, P<.001), indicating that the average drug-placebo difference significantly decreased over time, with decreasing baseline severity and with increasing study duration. Medication treatment in comparator studies was associated with significantly more improvement than medication treatment in placebo-controlled trials (t93=2.73, P=.008).Conclusions and relevanceThe average treatment change associated with placebo treatment in antipsychotic trials increased since 1960, while the change associated with medication treatment decreased. Changes in randomized clinical trials leading to inflation of baseline scores, enrollment of less severely ill participants, and higher expectations of patients may all be responsible.

Project description:BackgroundThe catechol-O-methyltransferase (COMT) enzyme plays a crucial role in dopamine degradation, and the COMT Val158Met polymorphism (rs4680) is associated with significant differences in enzymatic activity and consequently dopamine concentrations in the prefrontal cortex. Multiple studies have analyzed the COMT Val158Met variant in relation to antipsychotic response. Here, we conducted a meta-analysis examining the relationship between COMT Val158Met and antipsychotic response.MethodsSearches using PubMed, Web of Science, and PsycInfo databases (03/01/2015) yielded 23 studies investigating COMT Val158Met variation and antipsychotic response in schizophrenia and schizo-affective disorder. Responders/nonresponders were defined using each study's original criteria. If no binary response definition was used, authors were asked to define response according to at least 30% Positive and Negative Syndrome Scale score reduction (or equivalent in other scales). Analysis was conducted under a fixed-effects model.ResultsTen studies met inclusion criteria for the meta-analysis. Five additional antipsychotic-treated samples were analyzed for Val158Met and response and included in the meta-analysis (ntotal=1416). Met/Met individuals were significantly more likely to respond than Val-carriers (P=.039, ORMet/Met=1.37, 95% CI: 1.02-1.85). Met/Met patients also experienced significantly greater improvement in positive symptoms relative to Val-carriers (P=.030, SMD=0.24, 95% CI: 0.024-0.46). Posthoc analyses on patients treated with atypical antipsychotics (n=1207) showed that Met/Met patients were significantly more likely to respond relative to Val-carriers (P=.0098, ORMet/Met=1.54, 95% CI: 1.11-2.14), while no difference was observed for typical-antipsychotic-treated patients (n=155) (P=.65).ConclusionsOur findings suggest that the COMT Val158Met polymorphism is associated with response to antipsychotics in schizophrenia and schizo-affective disorder patients. This effect may be more pronounced for atypical antipsychotics.

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

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

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