Single nucleotide polymorphisms in C-reactive protein (CRP) predict response to adjunctive celecoxib treatment of resistant bipolar depression

Halaris, Angelos; Hain, Daniel S.; Law, Rebecca M.; Brown, Lisa M.; Lewis, David A.; Filip, Maria

doi:10.1016/j.bbih.2023.100625

Cited by 3 publications

(4 citation statements)

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“…We justified this preliminary hypothesis based on broader literature support that immune–metabolic dysregulation is a component of depressive neuroprogression, including in treatment-refractory forms of depressive illness. Prior studies in our TRBDD sample also revealed that treatment response to CBX augmentation were associated with pre-treatment abnormalities in inflammatory markers [ 22 , 23 ]. There were no independent effects of baseline SIRI on HAMD-17 (week 8) on either univariate or multivariate levels.…”

Section: Discussionmentioning

confidence: 71%

“…In a recent double-blind, placebo-controlled RCT in treatment-resistant bipolar depression (TRBDD), we demonstrated that clinical remission can be induced with adjunctive immune modulatory treatment with the selective cyclo-oxygenase 2 (COX2) inhibitor, celecoxib (CBX), in conjunction with an adequately dosed selective serotonin reuptake inhibitor (SSRI), escitalopram (ESC) [ 18 ]. Since then, we have conducted several follow-up biomarker studies to clarify group differences in TRBDD compared to healthy controls [ 19 , 20 , 21 , 22 , 23 ]. Specifically, we found evidence of elevated pre-treatment levels of baseline pro-inflammatory markers including interleukin-1 beta (IL-1β) and C-reactive protein (CRP) in TRBDD compared to healthy controls [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

“…From a metabolic standpoint, TRBDD subjects also showed abnormalities in the kynurenine pathway (KP), which diverts tryptophan (TRP) away from serotonin (5-HT) synthesis and towards various neuroactive metabolites in a cytokine-dependent manner [ 21 ]. We also explored markers involved in treatment responsiveness to adjunctive CBX in our TRBDD sample, including polymorphisms in the CRP gene and monocyte chemoattractant protein (MCP1) [ 22 , 23 ]. Taken together, these findings support the generally accepted concept that immune–metabolic dysfunction may contribute to the underlying biosignature of TRBDD thus indicating a likelihood of beneficial clinical response to adjunctive CBX.…”

Section: Introductionmentioning

confidence: 99%

“… Fourth, we hypothesized that pre-treatment (baseline) SIRI levels are associated with post-treatment clinical outcomes (depressive severity). This last hypothesis is based on the broader notion that treatment refractoriness is based, at least in part, on pre-existing immune–metabolic abnormalities in the literature and also our sample [ 22 , 23 ]. …”

Section: Introductionmentioning

confidence: 99%

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Systemic Inflammatory Response Index (SIRI) at Baseline Predicts Clinical Response for a Subset of Treatment-Resistant Bipolar Depressed Patients

Murata,

Baig,

Decker

et al. 2023

JPM

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Background: in a recent double-blind, placebo controlled RCT we demonstrated that selective inhibition of cyclo-oxygenase 2 (COX2) is an effective adjunctive strategy in treatment-resistant bipolar depression (TRBDD). To better clarify the mechanisms underlying TRBDD and treatment response, we conducted a retrospective exploratory analysis of the systemic inflammatory response index (SIRI = absolute neutrophils × absolute monocytes/absolute lymphocytes) in relation to other biomarkers and clinical outcomes after escitalopram (ESC), combined with the COX-2 inhibitor, celecoxib (CBX), versus placebo. Methods: Baseline measures of SIRI were compared between TRBDD and healthy controls (HC), and correlated with blood-based inflammatory cytokines, kynurenines, and growth factors. Post-treatment Hamilton Depression Rating Scale 17 (HAMD-17) total scores (clinical outcome) were modelled according to SIRI adjusting for demographics (including relevant interactions with SIRI), baseline depression, treatment arm, and treatment timepoint using multiple linear regression and robust linear mixed effects models. Results: Baseline SIRI did not distinguish TRBDD from HC groups. Baseline SIRI was significantly correlated with lower baseline MCP-1. The relationship between SIRI and HAMD-17 was significant at treatment week 8, in contrast to baseline. Finally, baseline SIRI predicted elevated post-treatment HAMD-17 scores, amongst patients with elevated depression scores at baseline. Significance: High pre-treatment SIRI may predict poorer depressive outcomes amongst TRBDD patients with baseline elevated depression.

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Section: Discussionmentioning

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Systemic Inflammatory Response Index (SIRI) at Baseline Predicts Clinical Response for a Subset of Treatment-Resistant Bipolar Depressed Patients

Murata,

Baig,

Decker

et al. 2023

JPM

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Tratamento anti-inflamatório na depressão: uma revisão sistemática

Costa Braga,

Costa,

Azevedo

2024

Debates em Psiquiatria

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Introdução: A alta prevalência de depressão na população mundial, associada à elevada morbidade do transtorno, torna necessário o desenvolvimento de tratamentos eficazes. Estudos recentes comprovaram a correlação entre inflamação e desenvolvimento de quadros depressivos. Objetivos: Avaliar o uso de substâncias anti-inflamatórias no manejo de pacientes com depressão uni e bipolar. Metodologia: Este estudo é uma revisão sistemática com análise qualitativa baseada no protocolo Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A busca foi realizada na Biblioteca Virtual em Saúde e PubMed. Sete estudos foram selecionados. Resultados: O número de estudos que mostraram eficácia do celecoxibe e do infliximabe foi próximo daqueles que não o foram, os biomarcadores séricos foram relacionados à diminuição das escalas de depressão com ambos. Conclusões: Os resultados sobre a eficácia do tratamento anti-inflamatório na depressão ainda são inconclusivos devido à heterogeneidade das pesquisas e ao baixo número de estudos disponíveis.

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Biomarkers in the Diagnosis and Prediction of Medication Response in Depression and the Role of Nutraceuticals

Beer,

Rae,

Semmler

et al. 2024

IJMS

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Depression continues to be a significant and growing public health concern. In clinical practice, it involves a clinical diagnosis. There is currently no defined or agreed upon biomarker/s for depression that can be readily tested. A biomarker is defined as a biological indicator of normal physiological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention that can be objectively measured and evaluated. Thus, as there is no such marker for depression, there is no objective measure of depression in clinical practice. The discovery of such a biomarker/s would greatly assist clinical practice and potentially lead to an earlier diagnosis of depression and therefore treatment. A biomarker for depression may also assist in determining response to medication. This is of particular importance as not all patients prescribed with medication will respond, which is referred to as medication resistance. The advent of pharmacogenomics in recent years holds promise to target treatment in depression, particularly in cases of medication resistance. The role of pharmacogenomics in routine depression management within clinical practice remains to be fully established. Equally so, the use of pharmaceutical grade nutrients known as nutraceuticals in the treatment of depression in the clinical practice setting is largely unknown, albeit frequently self-prescribed by patients. Whether nutraceuticals have a role in not only depression treatment but also in potentially modifying the biomarkers of depression has yet to be proven. The aim of this review is to highlight the potential biomarkers for the diagnosis, prediction, and medication response of depression.

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Single nucleotide polymorphisms in C-reactive protein (CRP) predict response to adjunctive celecoxib treatment of resistant bipolar depression

Cited by 3 publications

References 72 publications

Systemic Inflammatory Response Index (SIRI) at Baseline Predicts Clinical Response for a Subset of Treatment-Resistant Bipolar Depressed Patients

Systemic Inflammatory Response Index (SIRI) at Baseline Predicts Clinical Response for a Subset of Treatment-Resistant Bipolar Depressed Patients

Tratamento anti-inflamatório na depressão: uma revisão sistemática

Biomarkers in the Diagnosis and Prediction of Medication Response in Depression and the Role of Nutraceuticals

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