Dataset Information

Roles of C-reactive protein polymorphisms and life event changes on cognitive function in bipolar patients receiving valproate.

ABSTRACT:

Introduction

Patients with bipolar disorder (BD) exhibit an inflamed condition that is associated with metabolic disturbance and cognitive impairment. Whether inflammation, represented by C-reactive protein (CRP), is causally associated with BD and influences treatment outcome has not been established.

Methods

We examined whether CRP is a causal factor for the risk of BD in drug-naïve, depressed BD patients and investigated whether polymorphisms in CRP and life event changes influence cognitive function in BD patients receiving valproate (VPA) treatment.

Results

Our results showed that BD patients had significantly higher CRP levels and worse cognitive function than the controls, while the frequencies of CRP single nucleotide polymorphisms in BD patients and in controls were not different. In addition, the life event scale score was higher for BD patients than for controls. Furthermore, the genotypes of CRP polymorphisms and the interactions between polymorphisms of CRP and life event scale score had a significant influence on cognitive performance in BD patients after 12 weeks of VPA treatment.

Conclusion

Our study demonstrated the clinical utility of the application of functional genetics in clarifying the interactions among CRP, life event stress, and BD and suggested the important roles of CRP gene-environment interactions in developing treatment strategies for BD.

SUBMITTER: Chen PS

PROVIDER: S-EPMC8984865 | biostudies-literature | 2022 Jan-Dec

REPOSITORIES: biostudies-literature

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Publications

Roles of C-reactive protein polymorphisms and life event changes on cognitive function in bipolar patients receiving valproate.

Chen Po See PS Tang Li-Yi LY Chang Hui Hua HH

International journal of immunopathology and pharmacology 20220101

<h4>Introduction</h4>Patients with bipolar disorder (BD) exhibit an inflamed condition that is associated with metabolic disturbance and cognitive impairment. Whether inflammation, represented by C-reactive protein (CRP), is causally associated with BD and influences treatment outcome has not been established.<h4>Methods</h4>We examined whether CRP is a causal factor for the risk of BD in drug-naïve, depressed BD patients and investigated whether polymorphisms in <i>CRP</i> and life event change ...[more]

PMID: 35377256

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Project description:IntroductionBipolar disorder is characterized by severe mood symptoms including major depressive and manic episodes. During manic episodes, many patients show cognitive dysfunction. Dopamine and glutamate are important for cognitive processing, thus the COMT and DAOA genes that modulate the expression of these neurotransmitters are of interest for studies of cognitive function.MethodologyFocusing on the most severe episode of mania, a factor was found with the combined symptoms of talkativeness, distractibility, and thought disorder, considered a cognitive manic symptoms (CMS) factor. 488 patients were genotyped, out of which 373 (76%) had talkativeness, 269 (55%) distractibility, and 372 (76%) thought disorder. 215 (44%) patients were positive for all three symptoms, thus showing CMS (Table 1). As population controls, 1,044 anonymous blood donors (ABD) were used. Case-case and case-control design models were used to investigate genetic associations between cognitive manic symptoms in bipolar 1 disorder and SNPs in the COMT and DAOA genes. [Table: see text].ResultsThe finding of this study was that cognitive manic symptoms in patients with bipolar 1 disorder was associated with genetic variants in the DAOA and COMT genes. Nominal association for DAOA SNPs and COMT SNPs to cognitive symptoms factor in bipolar 1 disorder was found in both allelic (Table 2) and haplotypic (Table 3) analyses. Genotypic association analyses also supported our findings. However, only one association, when CMS patients were compared to ABD controls, survived correction for multiple testing by max (T) permutation. Data also suggested interaction between SNPs rs2391191 in DAOA and rs5993883 in COMT in the case-control model. [Table: see text] [Table: see text].ConclusionIdentifying genes associated with cognitive functioning has clinical implications for assessment of prognosis and progression. Our finding are consistent with other studies showing genetic associations between the COMT and DAOA genes and impaired cognition both in psychiatric disorders and in the general population.

Project description:BackgroundAffective illness has been associated with a proinflammatory state, and it is generally accepted that the immune system plays a key role in the pathophysiology of mood disorders. Since inflammatory biomarkers are elevated in bipolar disorder, anti-inflammatory combination therapies may enhance response and reverse treatment resistance.PurposeIn the present study we investigated the possible impact of single nucleotide polymorphisms (SNPs) within the CRP gene on CRP blood levels, treatment response and level-of-stress perception in our cohort of treatment-resistant bipolar-depressed patients receiving escitalopram and celecoxib, or escitalopram and placebo, as previously reported (Halaris et al., 2020).MethodsStudy design, clinical findings, and CRP blood levels have been reported previously (Halaris et al., 2020; Edberg et al., 2018). In this follow-up study we extracted DNA from blood cells collected at baseline. Genome-wide genotyping was performed for all subjects using the Infinium Multi-Ethnic Global-8 v1.0 Kit. Based on reports in the literature indicating possible associations with psychiatric conditions, ten previously reported CRP gene polymorphisms were evaluated in a preliminary analysis. We focused on rs3093059 and rs3093077 were in complete LD. Carriers were defined as those possessing at least one C allele for rs3093059, or at least one G allele for rs3093077. Additionally, we determined blood levels of the medications administered.ResultsNon-carriers of rs3093059 and rs3093077 had significantly lower baseline CRP blood levels than carriers (p = 0.03). Increased rates of HAM-D17 response (p = 0.21) and remission (p = 0.13) and lower PSS-14 scores (p = 0.13) were observed in non-carriers among subjects receiving celecoxib but they did not reach statistical significance. When examining all subjects, nominally significant associations between carrier-status and remission (p = 0.04) and PSS-14 scores (p = 0.04) were observed after correcting for treatment arm. Non-carriers receiving celecoxib had the highest rates of response and remission, and the lowest stress scores.ConclusionsCarriers of the CRP SNPs may have higher baseline CRP levels, although non-carriers appear to benefit more from celecoxib co-therapy. Determination of the carrier status in conjunction with pretreatment blood CRP level measurement may contribute to personalized psychiatric practice, but replication of the present findings is needed.

Dataset Information

Roles of C-reactive protein polymorphisms and life event changes on cognitive function in bipolar patients receiving valproate.

Introduction

Methods

Results

Conclusion

Publications

Roles of C-reactive protein polymorphisms and life event changes on cognitive function in bipolar patients receiving valproate.

Similar Datasets

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