Vascular endothelial growth factor in bipolar depression: A potential biomarker for diagnosis and treatment outcome prediction

Castillo, Monica Feliz R.; Cohen, A.; Edberg, David; Hoppensteadt, Debra; Fareed, Jawed; Martin, Brendan; Halaris, Angelos

doi:10.1016/j.psychres.2020.112781

Cited by 15 publications

(10 citation statements)

References 41 publications

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“…44 This antidepressant effect is associated with the ability of VEGF to improve cognitive function, promote neurogenesis, and facilitate 854 hippocampal synaptic plasticity. [45][46][47][48] Comprehensively, activation of the HIF-1α-VEGF signaling pathway may be implicated in the treatment of depression, which is highly consistent with our experimental results. Compared to the CUMS group, high and low doses of GRd can significantly increase mRNA and protein expression of hippocampal HIF-1α and VEGF in both the behavioral despair mouse model of depression and the rat CUMS model.…”

Section: Discussionsupporting

confidence: 90%

Antidepressant-Like Effect and Mechanism of Ginsenoside Rd on Rodent Models of Depression

Wang

Zhang

et al. 2022

DDDT

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Background: There is growing evidence to suggest that ginsenoside Rd (GRd) has a therapeutic effect on depression, but the specific mechanisms behind its activity require further study. Objective: This study is designed to investigate the antidepressant-like effect and underlying mechanisms of GRd. Methods: In this study, the behavioral despair mouse model of depression and chronic unpredictable mild stress (CUMS) rat model of depression were established to explore the effects of GRd on depression-like behavior and its underlying mechanisms. Behavioral tests were used to evaluate the replication of animal models and depression-like behaviors. The hypoxia-inducible factor-1α (HIF-1α) blocker 2-methoxyestradiol (2-ME) was injected to determine the role of HIF-1α in the antidepressant-like effect of GRd. In addition, molecular biology techniques were used to determine the mRNA and protein expression of HIF-1ɑ signaling pathway and synaptic plasticity-related regulators, that is synapsin 1 (SYN 1) and postsynaptic density protein 95 (PSD 95). In silico binding interaction studies of GRd with focused target proteins were performed using molecular docking to predict the affinity and optimal binding mode between ligands and receptors. Results: Our data show that GRd significantly reversed depression-like behavior and promoted mRNA and protein expression of HIF-1ɑ signaling pathway and synaptic plasticity-related regulators. However, the antidepressant-like effect of GRd disappeared upon inhibition of HIF-1α expression following administration of 2-ME. Furthermore, molecular docking results showed that GRd possessed significant binding affinity for HIF-1α, VEGF, and VEGFR-2. Conclusion: Our results show that GRd exhibits significant antidepressant-like effect and that HIF-1α signaling pathway is a promising target for the treatment of depression.

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Section: Discussionsupporting

confidence: 90%

Antidepressant-Like Effect and Mechanism of Ginsenoside Rd on Rodent Models of Depression

Wang

Zhang

et al. 2022

DDDT

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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%

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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“… Post-hoc analyses of the above mentioned RCT ( Halaris A et al 2020 39 ) Edberg et al, 2020 47 Post-hoc analysis Escitalopram (10–40 daily) + Celecoxib (200 mg twice daily) vs Escitalopram (10–40 daily) + placebo (twice daily) 47 Plasma MCP-1 levels MCP-1 levels were not different in BDD vs HC subjects. Castillo et al, 2020 45 Post-hoc analysis Escitalopram (10–40 daily) + Celecoxib (200 mg twice daily) vs Escitalopram (10–40 daily) + placebo (twice daily) 32 HC 47 BD VEGF levels VEGF was significantly higher at baseline in BD patients compared to HC. No difference between BD groups after treatment.…”

Section: Methodsmentioning

confidence: 99%

“…Two post-hoc analyses revealed that BD patients had significantly higher vascular endothelial growth factor levels at baseline that did not change with treatment, and C-reactive protein that decreased significantly more with treatment when compared to placebo. 45,46 Monocyte chemoattractant protein-1 was negatively correlated in treatment non-responders and thus could predict response. 47 Insulin resistance in type 2 diabetes mellitus is a risk factor of BD.…”

mentioning

confidence: 99%

Treatment-Resistant Bipolar Depression: Therapeutic Trends, Challenges and Future Directions

Elsayed¹,

Ercis²,

Pahwa³

et al. 2022

NDT

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Introduction Bipolar disorder (BD) is a chronic mental illness impacting 1–2% of the population worldwide and causing high rates of functional impairment. Patients with BD spend most of their time in depressive episodes and up to one-third of patients do not respond to adequate doses of medications. Although no consensus exists for definition of treatment-resistant bipolar depression (TRBD), failure of symptoms improvement despite an adequate trial of two therapeutic agents is a common theme of TRBD. In this paper, we review the evidence base of therapeutic interventions, challenges, and potential future directions for TRBD. Methods We conducted a literature search for randomized controlled trials on PubMed for the treatment of TRBD and ongoing trials for the treatment of TRBD/bipolar depression on clinicaltrials.gov. Results Several therapeutic agents have been investigated for TRBD. Adjunctive pramipexole and modafinil have data supporting short-term efficacy in TRBD, along with limited data for racemic intravenous ketamine. Celecoxib augmentation of escitalopram and treatment with metformin in patients with insulin resistance showed promising results. Right unilateral electroconvulsive therapy displayed statistically significant response rate and improvement, but not remission compared to pharmacotherapy. Trials for transcranial magnetic stimulation (TMS) have failed to show a significant difference from sham treatment in TRBD. Future Trends Pharmacological treatments with novel mechanisms of actions like brexpiprazole and vortioxetine are being investigated following successes in unipolar depression. Modified TMS protocols such as accelerated TMS are under investigation. Innovative approaches like psychedelic-assisted psychotherapy, interleukin-2, fecal microbiota transplantation and multipotent stromal cells are being studied. Conclusion Evidence on current treatment modalities for TRBD is limited with low efficacy. More research is needed for successful treatment of TRBD. Effective therapies and innovative approaches to treatment are being investigated and could show promise.

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Vascular endothelial growth factor in bipolar depression: A potential biomarker for diagnosis and treatment outcome prediction

Cited by 15 publications

References 41 publications

Antidepressant-Like Effect and Mechanism of Ginsenoside Rd on Rodent Models of Depression

Antidepressant-Like Effect and Mechanism of Ginsenoside Rd on Rodent Models of Depression

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

Treatment-Resistant Bipolar Depression: Therapeutic Trends, Challenges and Future Directions

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