1.
Antidepressant pathways of the Chinese herb jiaweisinisan through genetic ontology analysis.
Chen, J, Huang, Y, Li, L, Niu, J, Ye, W, Wang, Y, Yan, C, Wu, L
Journal of integrative neuroscience. 2020;(2):385-395
Abstract
Active compounds and corresponding targets of the traditional Chinese herb, jiaweisinisan, were obtained from systems pharmacological database and placed into ClueGO for gene ontology analysis. The targets of depression were obtained from the Online Mendelian Inheritance in Man, the Therapeutic Target Database, and the Pharmacogenomics Knowledge Base. Compound-target and target-pathway networks were constructed using Cytoscape, and then their topological parameters were analyzed. The targets of jiaweisinisan and depression were mapped to pathways, thereby constructing antidepressant pathways of jiaweisinisan. It was found that jiaweisinisan has 82 different active compounds and 306 relevant potential targets. Also, 107 unrepeatable targets related to depression were found. In all, 26 common targets were found to be the direct anti-depression targets of jiaweisinisan and 9 pathways of jiaweisinisan related to depression were divided into three modules (synaptic transmission, cell apoptosis, and immune-inflammatory). The jiaweisinisan formula was found to have synergistic antidepressant effects due to aspects of its herb composition and the active compounds therein, giving rise to potential targets and signaling pathways related to depression. Its antidepressant mechanisms were found to mainly involve the regulation of synaptic transmission, cell apoptosis, and immune-mediated inflammation.
2.
Transcriptional signatures related to glucose and lipid metabolism predict treatment response to the tumor necrosis factor antagonist infliximab in patients with treatment-resistant depression.
Mehta, D, Raison, CL, Woolwine, BJ, Haroon, E, Binder, EB, Miller, AH, Felger, JC
Brain, behavior, and immunity. 2013;:205-15
-
-
Free full text
-
Abstract
The tumor necrosis factor (TNF) antagonist infliximab was recently found to reduce depressive symptoms in patients with increased baseline inflammation as reflected by a plasma C-reactive protein concentration >5 mg/L. To further explore predictors and targets of response to infliximab, differential gene expression was examined in peripheral blood mononuclear cells from infliximab responders (n=13) versus non-responders (n=14) compared to placebo at baseline and 6 h, 24 h, and 2 weeks after the first infliximab infusion. Treatment response was defined as 50% reduction in depressive symptoms at any point during the 12-week trial. One-hundred-forty-eight gene transcripts were significantly associated (1.2-fold, adjusted p≤0.01) with response to infliximab and were distinct from placebo responders. Transcripts predictive of infliximab response were associated with gluconeogenesis and cholesterol transport, and were enriched in a network regulated by hepatocyte nuclear factor (HNF)4-alpha, a transcription factor involved in gluconeogenesis and cholesterol and lipid homeostasis. Of the 148 transcripts differentially expressed at baseline, 48% were significantly regulated over time in infliximab responders, including genes related to gluconeogenesis and the HNF4-alpha network, indicating that these predictive genes were responsive to infliximab. Responders also demonstrated inhibition of genes related to apoptosis through TNF signaling at 6 h and 24 h after infusion. Transcripts down-regulated in responders 2 weeks after infliximab were related to innate immune signaling and nuclear factor-kappa B. Thus, baseline transcriptional signatures reflective of alterations in glucose and lipid metabolism predicted antidepressant response to infliximab, and infliximab response involved regulation of metabolic genes and inhibition of genes related to innate immune activation.
3.
Metabolic syndrome and C-reactive protein in patients with depressive disorder on antidepressive medication.
Stanojević, A, Popović, I, Nenadović, M, Ravanić, D, Paunović-Milosavljević, G
Srpski arhiv za celokupno lekarstvo. 2013;(7-8):511-5
Abstract
INTRODUCTION Recurrent depression is a psychiatric disorder of which etiology and pathogenesis might be related to immune response. Metabolic Syndrome (MetS) and its components are also strongly associated with elevated inflammatory indicators, as so as the body mass index (BMI) and total cholesterol levels. OBJECTIVE Objective of this study was to investigate if there was any difference in C-reactive protein (CRP) levels in patients with recurrent depressive disorder, treated with antidepressants, compared to a healthy control group of subjects and if there was an association between increased CRP levels and the presence of MetS in these two groups. METHODS Sixty subjects entered the study; of these 35 patients with the diagnosis of recurrent depressive disorder, while the healthy control group included 25 subjects. MetS was defined according to the NCEP ATP III criteria. The cut-off point for CRP was set at > 5 mg/L. RESULTS There was no statistically significant difference in the prevalence of MetS and CRP values between the studied groups. Waist circumference and total cholesterol levels were significantly higher in the experimental group. Patients that fulfilled the criteria for MetS showed significantly higher values of central obesity and arterial hypertension in the experimental group as well. The elevated CRP levels were associated with increased frequency of MetS in depressed patients. CONCLUSION Both CRP levels and metabolic risk profile screening, according to the international criteria, may be beneficial in order to obtain better assessment for depressive long-term medicated patients.
4.
Effect of zinc supplementation on antidepressant therapy in unipolar depression: a preliminary placebo-controlled study.
Nowak, G, Siwek, M, Dudek, D, Zieba, A, Pilc, A
Polish journal of pharmacology. 2003;(6):1143-7
Abstract
A growing body of evidence implicates a derangement of zinc homeostasis in mood disorders. In general, unipolar depression is connected with low blood zinc levels that are increased by effective antidepressant therapy. A placebo-controlled, double blind pilot study of zinc supplementation in antidepressant therapy was conducted in patients who fulfilled DSM IV criteria for major (unipolar) depression. Patients received zinc supplementation (6 patients; 25 mg of Zn2+ once daily) or placebo (8 patients) and were treated with standard antidepressant therapy (tricyclic antidepressants, selective serotonin reuptake inhibitors). Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI) were used to assess efficacy of antidepressant therapy, and patients' status was evaluated before the treatment and 2, 6 and 12 weeks after its commencement. Antidepressant treatment significantly reduced HDRS scores by the 2nd week of treatment in both groups, and lowered BDI scores at the 6th week in zinc-treated group. Zinc supplementation significantly reduced scores in both measures after 6- and 12-week supplementation when compared with placebo treatment. This preliminary study is the first demonstration of the benefit of zinc supplementation in antidepressant therapy. The mechanism(s) may be related to modulation of glutamatergic or immune systems by zinc ion.