Dataset Information

Elevated C-reactive protein associated with late- and very-late-onset schizophrenia in the general population: a prospective study.

ABSTRACT:

Background

Individuals with autoimmune diseases and severe infections have persistent or acutely elevated inflammatory biomarkers and increased risk of schizophrenia. We tested the hypothesis that baseline elevated plasma levels of the inflammatory biomarker, C-reactive protein (CRP), associate with increased risk of late- and very-late-onset schizophrenia in the general population, and if such an association possibly is causal.

Method

We analyzed data from 78 810 men and women, aged 20-100 years, from 2 large population studies. Endpoints were hospitalization with schizophrenia and schizophrenia and schizophrenia-like psychosis combined. We performed prospective and cross-sectional analyses adjusted for potential confounders with up to 20 years of follow-up. Furthermore, we used genetic variants influencing plasma CRP levels to perform a Mendelian randomization study.

Results

Age- and gender-adjusted hazard ratios vs individuals in the first quartile of CRP were 1.7 (95% CI: 0.3-8.9) for second quartile, 2.1 (0.4-10) for third quartile, and 11 (2.8-40) for fourth quartile individuals. The corresponding hazard ratio for fourth quartile individuals after multifactorial adjustment was 5.9 (1.4-24). Furthermore, individuals with vs without schizophrenia had 63% increased plasma levels of CRP (P = 1 × 10(-4)). Finally, when CRP was on a continuous scale, a doubling in CRP yielded an age- and gender-adjusted observational OR of 1.5 (1.3-1.8) and a corresponding causal OR of 1.4 (0.5-4.3) (observed vs causal: P = .89).

Conclusion

Baseline elevated plasma CRP is associated with a 6- to 11-fold increased risk of late- and very-late-onset schizophrenia in the general population. We cannot exclude that this is a causal association. These are novel findings.

SUBMITTER: Wium-Andersen MK

PROVIDER: S-EPMC4133657 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Publications

Elevated C-reactive protein associated with late- and very-late-onset schizophrenia in the general population: a prospective study.

Wium-Andersen Marie Kim MK Ørsted David Dynnes DD Nordestgaard Børge Grønne BG

Schizophrenia bulletin 20130831 5

<h4>Background</h4>Individuals with autoimmune diseases and severe infections have persistent or acutely elevated inflammatory biomarkers and increased risk of schizophrenia. We tested the hypothesis that baseline elevated plasma levels of the inflammatory biomarker, C-reactive protein (CRP), associate with increased risk of late- and very-late-onset schizophrenia in the general population, and if such an association possibly is causal.<h4>Method</h4>We analyzed data from 78 810 men and women, a ...[more]

PMID: 23996346

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Project description:BackgroundVery late (aged ≥60 years) onset schizophrenia-like psychosis occurs frequently but no placebo-controlled, randomised trials have assessed the efficacy and risks of antipsychotic treatment. We investigated whether low-dose amisulpride (100 mg daily) is superior to placebo in reducing psychosis symptoms over 12 weeks and whether any benefit is maintained by continuing treatment after 12 weeks.MethodsThe ATLAS double-blind controlled trial enrolled participants from 25 old age psychiatry services in the UK. Eligible participants (ie, those with a diagnosis of very late-onset schizophrenia-like psychosis and a Brief Psychiatric Rating Scale [BPRS] score of ≥30, without cognitive impairment) were randomly assigned (1:1:1) to one of three groups in a two-stage trial: amisulpride in stage 1 and 2 (group A), amisulpride then placebo (group B), or placebo then amisulpride (group C). Treatment (100 mg oral amisulpride daily vs placebo) was given for 12 weeks in stage 1 and, initially, 24 weeks then reduced to 12 weeks in stage 2. Participants, investigators, and outcome assessors were masked to treatment allocation. Primary outcomes were psychosis symptoms assessed by the BPRS at 4, 12, and 24, or 36 weeks, and trial treatment discontinuation for non-efficacy. The primary, secondary, and safety endpoints were all analysed in participants given at least one dose of study treatment in modified intention-to-treat analyses. This study is registered with EudraCT, number 2010-022184-35, and ISRCTN, number ISRCTN45593573.FindingsBetween Sept 27, 2012, and June 28, 2016, we recruited 101 participants. 92 (91%) of 101 participants took trial medication, of whom 59 (64%) completed stage 1 and 34 (58%) of these 59 participants completed stage 2 treatment. Despite suboptimal compliance, improvements in BPRS scores at 12 weeks were 7·7 points (95% CI 3·8-11·5, p=0·0002) greater with amisulpride (mean 11·9 points [SE 1·3]) than with placebo (4·2 points [1·0]). In stage 2, BPRS scores improved by a mean of 1·1 points (1·6) from 12 weeks to the final assessment in those who continued amisulpride but deteriorated by 5·2 points (2·0) in those who switched from amisulpride to placebo (difference 6·3 points [95% CI 0·9-11·7], p=0·024). Fewer participants who were allocated amisulpride than placebo stopped treatment because of non-efficacy in stage 1 (p=0·010) and stage 2 (p=0·031). Serious adverse events were reported more frequently in the amisulpride group than in the placebo group in stage 1 (p=0·057) and stage 2 (p=0·19). The most common serious adverse events were infection (five patients in the amisulpride group, three in the placebo group) and extrapyramidal side-effects (three patients in the amisulpride group, none in the placebo group). Five patients died during the study, one from a gastric ulcer bleed before treatment started (group B), two while taking stage 2 treatment (one in group A and one in group C), and two who stopped trial treatment in stage 1 and died many weeks later (one in group B and one in group C). No deaths were related to treatment.InterpretationLow-dose amisulpride is effective and well tolerated as a treatment for very late-onset schizophrenia-like psychosis, with benefits maintained by prolonging treatment.FundingUK National Institute for Health Research.

Project description:BACKGROUND:Host immune responses during late-onset sepsis (LOS) in very preterm infants are poorly characterised due to a complex and dynamic pathophysiology and challenges in working with small available blood volumes. We present here an unbiased transcriptomic analysis of whole peripheral blood from very preterm infants at the time of LOS. METHODS:RNA-Seq was performed on peripheral blood samples (6-29 days postnatal age) taken at the time of suspected LOS from very preterm infants <30 weeks gestational age. Infants were classified based on blood culture positivity and elevated C-reactive protein concentrations as having confirmed LOS (n = 5), possible LOS (n = 4) or no LOS (n = 9). Bioinformatics and statistical analyses performed included pathway over-representation and protein-protein interaction network analyses. Plasma cytokine immunoassays were performed to validate differentially expressed cytokine pathways. RESULTS:The blood leukocyte transcriptional responses of infants with confirmed LOS differed significantly from infants without LOS (1,317 differentially expressed genes). However, infants with possible LOS could not be distinguished from infants with no LOS or confirmed LOS. Transcriptional alterations associated with LOS included genes involved in pathogen recognition (mainly TLR pathways), cytokine signalling (both pro-inflammatory and inhibitory responses), immune and haematological regulation (including cell death pathways), and metabolism (altered cholesterol biosynthesis). At the transcriptional-level cytokine responses during LOS were characterised by over-representation of IFN-?/?, IFN-?, IL-1 and IL-6 signalling pathways and up-regulation of genes for inflammatory responses. Infants with confirmed LOS had significantly higher levels of IL-1? and IL-6 in their plasma. CONCLUSIONS:Blood responses in very preterm infants with LOS are characterised by altered host immune responses that appear to reflect unbalanced immuno-metabolic homeostasis.

Dataset Information

Elevated C-reactive protein associated with late- and very-late-onset schizophrenia in the general population: a prospective study.

Background

Method

Results

Conclusion

Publications

Elevated C-reactive protein associated with late- and very-late-onset schizophrenia in the general population: a prospective study.

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