Cytokine- and Vascular Endothelial Growth Factor-Related Gene-Based Genome-Wide Association Study of Low-Dose Ketamine Infusion in Patients with Treatment-Resistant Depression

Tsai, Shih‐Jen; Kao, Chung-Feng; Su, Tung‐Ping; Li, Cheng Ta; Lin, Wei‐Chen; Hong, Chien Tai; Bai, Ya‐Mei; Tu, Pei-Chi; Chen, Mu Hong

doi:10.1007/s40263-023-00989-7

Cited by 6 publications

(4 citation statements)

References 35 publications

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“…The conceptual significance of SIRI here may fit the ongoing discussion on the “cross-talk” between peripheral and CNS inflammation as it relates to depressive etiology [ 57 ]. Dysfunction at the vascular–endothelial interface is increasingly relevant here, especially considering reports of abnormal vascular endothelial growth factor (VEGF) in treatment-refractory depression [ 58 , 59 , 60 , 61 , 62 , 63 , 64 ]. SIRI adds to this discussion by bringing to bear the aspect of activated circulating immune cells (specifically monocytes, which are factored into SIRI), which are known to undergo trans-endothelial migration to promote microglial activation and thus neuroinflammation [ 28 , 65 , 66 , 67 , 68 , 69 ].…”

Section: Discussionmentioning

confidence: 99%

“…Successful placebo non-responders were randomized in a 1:1 fixed assignment ratio to receive either ESC + CBX or ESC + PBO. The approach to stratification included two age groups, and (46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65), plus binary genders (male, female), and group assignment was based on a pharmacy-generated randomization code. The randomization code was generated by the institutional pharmacist.…”

Section: Methodsmentioning

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: 99%

Section: Methodsmentioning

confidence: 99%

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

View full text Add to dashboard Cite

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“…Significant limitations of the mentioned studies are that they had different sample sizes (tens to thousands). Clinical samples in some of the studies were generally small (less than 100 samples) [37,55,78] and were underpowered for reliable detection of associations between neuroinflammation and mental disorders. Future studies with larger sample sizes are needed to explore these associations.…”

Section: Discussionmentioning

confidence: 99%

“…The results of the GWAS, published this year, suggest that specific SNPs, including rs2540315 and rs75746675 in the IL-1 receptor gene IL1R1, were associated with a rapid (within 240 min) antidepressant effect of ketamine infusion in patients with treatmentresistant depression [37]. An important limitation of the study is the small number of people examined (65 patients with treatment-resistant depression divided into 3 groups).…”

Section: Santos Et Al (2016) [50]mentioning

confidence: 99%

Association of Single Nucleotide Polymorphisms of Cytokine Genes with Depression, Schizophrenia and Bipolar Disorder

Mikhalitskaya

Vyalova

Ermakov

et al. 2023

Genes

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Immune gene variants are known to be associated with the risk of psychiatric disorders, their clinical manifestations, and their response to therapy. This narrative review summarizes the current literature over the past decade on the association of polymorphic variants of cytokine genes with risk, severity, and response to treatment for severe mental disorders such as bipolar disorder, depression, and schizophrenia. A search of literature in databases was carried out using keywords related to depressive disorder, bipolar disorder, schizophrenia, inflammation, and cytokines. Gene lists were extracted from publications to identify common genes and pathways for these mental disorders. Associations between polymorphic variants of the IL1B, IL6, and TNFA genes were the most replicated and relevant in depression. Polymorphic variants of the IL1B, IL6, IL6R, IL10, IL17A, and TNFA genes have been associated with schizophrenia. Bipolar disorder has mainly been associated with polymorphic variants of the IL1B gene. Interestingly, the IL6R gene polymorphism (rs2228145) was associated with all three diseases. Some cytokine genes have also been associated with clinical presentation and response to pharmacotherapy. There is also evidence that some specific polymorphic variants may affect the expression of cytokine genes. Thus, the data from this review indicate a link between neuroinflammation and severe mental disorders.

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Migraine and treatment-resistant depression

Chen

2023

Progress in Brain Research

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Cytokine- and Vascular Endothelial Growth Factor-Related Gene-Based Genome-Wide Association Study of Low-Dose Ketamine Infusion in Patients with Treatment-Resistant Depression

Cited by 6 publications

References 35 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

Association of Single Nucleotide Polymorphisms of Cytokine Genes with Depression, Schizophrenia and Bipolar Disorder

Migraine and treatment-resistant depression

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