Effects of zinc supplementation on efficacy of antidepressant therapy, inflammatory cytokines, and brain-derived neurotrophic factor in patients with major depression

Ranjbar, Elham; Shams, Jamal; Sabetkasaei, Masoumeh; M-Shirazi, Minoo; Rashidkhani, Bahram; Mostafavi, Seyed Ali; Bornak, Eiliyaz; Nasrollahzadeh, Javad

doi:10.1179/1476830513y.0000000066

Cited by 76 publications

(61 citation statements)

References 51 publications

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“…Conversely, chronic treatment with zinc, similar to conventional antidepressants, (Balu et al, 2008;De Foubert et al, 2004) was reported to increase BDNF mRNA and protein levels in the hippocampus (Cieslik et al, 2011;Sowa-Kucma et al, 2008) or cerebral cortex (Nowak et al, 2004) of rats. Interestingly, clinical studies also report that while zinc monotherapy (30 mg for 12 weeks) increased serum BDNF levels and decreased depressive symptoms in overweight or obese subjects (Solati et al, 2014), zinc supplementation (25 mg for 12 weeks) combined with selective serotonin reuptake inhibitor antidepressants reduced depressive symptoms, but did not change plasma levels of BDNF (Ranjbar et al, 2014).…”

Section: Discussionmentioning

confidence: 96%

Antidepressant-like effect of zinc is dependent on signaling pathways implicated in BDNF modulation

Manosso

Moretti

Ribeiro

et al. 2015

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Considering that intracellular signaling pathways that modulate brain BDNF are implicated in antidepressant responses, this study investigated whether signaling pathway inhibitors upstream to BDNF might influence the antidepressant-like effect of zinc, a metal that has been shown to display antidepressant properties. To this end, the influence of i.c.v. administration of H-89 (1μg/site, PKA inhibitor), KN-62 (1μg/site, CAMKII inhibitor), chelerythrine (1μg/site, PKC inhibitor), PD98059 (5μg/site, MEK1/2 inhibitor), U0126 (5μg/site, MEK1/2 inhibitor), LY294002 (10nmol/site, PI3K inhibitor) on the reduction of immobility time in the tail suspension test (TST) elicited by ZnCl2 (10mg/kg, p.o.) was investigated. Moreover, the effect of the combination of sub-effective doses of ZnCl2 (1mg/kg, p.o.) and AR-A014418 (0.001μg/site, GSK-3β inhibitor) was evaluated. The occurrence of changes in CREB phosphorylation and BDNF immunocontent in the hippocampus and prefrontal cortex of mice following ZnCl2 treatment was also investigated. The anti-immobility effect of ZnCl2 in the TST was prevented by treatment with PKA, PKC, CAMKII, MEK1/2 or PI3K inhibitors. Furthermore, ZnCl2 in combination with AR-A014418 caused a synergistic anti-immobility effect in the TST. None of the treatments altered locomotor activity of mice. ZnCl2 treatment caused no alteration in CREB phosphorylation and BDNF immunocontent. The results extend literature data regarding the mechanisms underlying the antidepressant-like action of zinc by indicating that its antidepressant-like effect may be dependent on the activation of PKA, CAMKII, PKC, ERK, and PI3K/GSK-3β pathways. However, zinc is not able to acutely increase BDNF in the hippocampus and prefrontal cortex.

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Section: Discussionmentioning

confidence: 96%

Antidepressant-like effect of zinc is dependent on signaling pathways implicated in BDNF modulation

Manosso

Moretti

Ribeiro

et al. 2015

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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“…IL-6R is a substrate of both types of ADAM proteases, whereas ADAM17 is primarily involved in generating sIL-6R and initiating IL-6 trans-signaling during pathological conditions. The shedding of IL-6R is further induced by phorbol ester phorbol-12-myristate-13-acetate, Opposing evidence [193] Zinc sulfate (25 mg/day) + SSRI (n = 20), placebo + SSRI (n = 17)…”

Section: Optimization Of Anti-il-6 Treatment Approaches In Mdd Via Sementioning

confidence: 92%

Novel investigational drugs targeting IL-6 signaling for the treatment of depression

Fonseka

McIntyre

Soczynska

et al. 2015

Expert Opinion on Investigational Drugs

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To improve drug development for the treatment of MDD, there is a critical need to identify promising targets. Target identification will require guidance from a strategic framework such as The Research Domain Criteria, and convincing evidence relating known targets to brain function under both physiological and pathological conditions. Although current evidence provides rationale for administering anti-IL-6 treatments in MDD, further studies confirming safety, target affinity and therapeutic benefits are warranted.

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“…We did not include studies measuring the effect of non-pharmacological depression treatments or studies with the use of ketamine or pharmacological agents not registered as antidepressants. We did however partially include some studies (Brunoni et al 2014, Ranjbar et al 2014, Hernandez et al 2014, Abbasi et al 2012, Mackay et al 2009, Jazayeri et al 2010) examining the effect of other than antidepressant therapies with the control group (e.g. treated with an SSRI) meeting our inclusion criteria.…”

Section: Systematic Search and Criteriamentioning

confidence: 99%

Effect of antidepressant treatment on peripheral inflammation markers – A meta-analysis

Więdłocha

Marcinowicz

Krupa

et al. 2018

Progress in Neuro-Psychopharmacology and Biological Psychiatry

176

106

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Effects of zinc supplementation on efficacy of antidepressant therapy, inflammatory cytokines, and brain-derived neurotrophic factor in patients with major depression

Abstract: Zinc supplementation in conjunction with antidepressant drugs might be beneficial for reducing depressive symptoms. However, its effect does not appear to be mediated through impact of zinc on inflammatory processes.

Cited by 76 publications

References 51 publications

Antidepressant-like effect of zinc is dependent on signaling pathways implicated in BDNF modulation

Antidepressant-like effect of zinc is dependent on signaling pathways implicated in BDNF modulation

Novel investigational drugs targeting IL-6 signaling for the treatment of depression

Effect of antidepressant treatment on peripheral inflammation markers – A meta-analysis

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