Brief report
Serum zinc level in depressed patients during zinc supplementation of imipramine treatment

https://doi.org/10.1016/j.jad.2010.04.024Get rights and content

Abstract

Background

Recurrent major depression is associated with decreased blood zinc concentrations that may be increased by effective antidepressant therapy. Some clinical investigations point to alterations of the zinc level in blood as a potential marker of depression.

Methods

A placebo-controlled, double blind study of zinc supplementation to imipramine therapy was conducted on sixty patients fulfilling the DSM-IV criteria for major depression (18–55 years old, 40 females, 20 males). Moreover, a group of 25 healthy volunteers was recruited (16 females, 9 males). Blood samples were drawn for the assay of serum zinc once from the control subjects and four times (before, and then 2, 6 and 12 weeks after the beginning of treatment) from the depressed subjects.

Results

We report that: 1) the serum zinc level was significantly lower (by 22%) in depressed patients than in healthy volunteers, 2) all groups demonstrated a gradual increase in zinc concentrations over the period of imipramine treatment with or without zinc supplementation, 3) treatment-resistant patients demonstrated lower concentrations of zinc (by 14%) than treatment-non-resistant patients, 4) zinc concentrations were higher in zinc-supplemented patients than in placebo-supplemented patients, 5) zinc supplementation increased zinc concentrations over the period of treatment, and 6) at a 12-week imipramine treatment, a significant negative correlation was demonstrated between the Montgomery–Asberg Depression Rating Scale and the serum zinc level together with a concomitant increase in serum zinc in patients in remission.

Conclusions

Serum zinc is a state marker of depression.

Introduction

Depression is considered as a chronic and recurring illness. The development of new medications for depression has been hindered by an insufficient knowledge on the pathophysiology of this disorder (Skolnick et al., 2009). Among other factors, a major obstacle in the diagnosis and effective therapy is the lack of biomarkers allowing assessment of the current depressive state. The discovery of such a marker could also be useful in predicting the risk of development of the disease and/or its relapse as well as its resistance to treatment. Some potential candidate markers of depression have been reported [e.g. (Dinan, 2009, Piccinni et al., 2009, Maes et al., 2010], but their relationships to the mechanisms of the pathophysiology of depression and efficacy in clinical practice are at present unclear.

Current hypotheses of depression are based on the alteration of neurotransmission, yet mostly of the monoaminergic and amino-acidergic systems (Skolnick et al., 2001, Palucha and Pilc, 2005, Pilc and Nowak, 2005). Recent data points to the involvement of zinc – a modulator of glutamatergic neurotransmission – in mood disorders and in the mechanism(s) of antidepressant activity (Nowak et al., 2005, Szewczyk et al., 2008, Szewczyk et al., 2010b). Preclinical studies have demonstrated the antidepressant-like activity of zinc in animal tests and models (Cieslik et al., 2007, Kroczka et al., 2000, Kroczka et al., 2001, Nowak et al., 2003b, Rosa et al., 2003, Sowa-Kucma et al., 2008). Moreover, zinc has been shown to enhance the activity of antidepressant drugs (Cieslik et al., 2007, Cunha et al., 2008, Kroczka et al., 2001, Szewczyk et al., 2002, Szewczyk et al., 2009), while zinc deficiency produced depressive-like alterations in behavioral and neurochemical studies (Corniola et al., 2008, Takeda and Tamano, 2009, Tassabehji et al., 2008, Whittle et al., 2009). Some clinical studies have indicated the reduction of the blood zinc level in depressed patients (Amani et al., 2010, Maes et al., 1994, Maes et al., 1997a, McLoughlin and Hodge, 1990, Nowak et al., 1999). Our previous clinical study demonstrated that zinc enhanced antidepressant efficacy in, especially, treatment-resistant patients suffering from major depression (Nowak et al., 2003a, Siwek et al., 2009).

The present study examined the effect of zinc supplementation to imipramine treatment on the serum zinc level in depressed patients.

Section snippets

Subjects

Sixty patients admitted to the Department of Psychiatry Jagiellonian University Collegium Medicum or to the Affective Disorder Outpatients Unit and fulfilling the DSM-IV criteria for major depression were accepted for the study [18–55 years old, details described previously (Siwek et al., 2009)].

A group of 25 healthy volunteers (normal controls) was also recruited. The normal controls (18–55 years old) were free of mental disorders and had no family history of depression or mania. In the normal

Results

The characteristics of the patients and the effect of the treatment on their psychopathological status were previously published by Siwek et al. (2009). The mean ages (± SD) in the volunteers and patients were 43 ± 9.1 and 45.9 ± 5.9 years, respectively, and did not significantly differ (P = 0.08). There were no significant differences in the female/male ratio between the volunteer (16/9) and patient group (40/20) (P = 0.81).

The analysis of zinc concentrations with ANOVA (Fig. 1) revealed that all of the

Discussion

The present study reports the first analysis of the changes in the serum zinc level in depressed patients receiving zinc supplementation of the uniform treatment regime (imipramine + placebo or zinc). All previous studies enrolled patient groups treated with various antidepressant drugs and a combination therapy (McLoughlin and Hodge, 1990, Schlegel-Zawadzka et al., 2000, Maes et al., 1996, Maes et al., 1997b, Maes et al., 1999).

The fact that significantly lower serum zinc concentrations existed

Role of funding source

This study was partially supported by Grant POIG 01.01.02-12-004/09, Funds for Statutory Activity of the Institute of Pharmacology, Polish Academy of Sciences and Jagiellonian University, Kraków, Poland, but had no further role in the study design, in the collection, analysis and interpretation of data, in the writing of the report and in the decision to submit the paper for publication.

Conflict of interest

The authors have no conflict of interest.

Acknowledgement

Authors thank “Farmapol” Sp. z o.o., Poznań, Poland for the generous gift of Zincas and placebo.

References (42)

  • G. Nowak et al.

    Antidepressant-like effects of acute and chronic treatment with zinc in forced swim test and olfactory bulbectomy model in rats

    Brain Res. Bull.

    (2003)
  • A. Piccinni et al.

    Plasma Brain-Derived Neurotrophic Factor in treatment-resistant depressed patients receiving electroconvulsive therapy

    Eur. Neuropsychopharmacol.

    (2009)
  • A.O. Rosa et al.

    Involvement of NMDA receptors and l-arginine-nitric oxide pathway in the antidepressant-like effects of zinc in mice

    Behav. Brain Res.

    (2003)
  • M. Siwek et al.

    Zinc supplementation augments efficacy of imipramine in treatment-resistant patients: a double-blind, placebo-controlled study

    J. Affect. Disord.

    (2009)
  • P. Skolnick et al.

    Glutamate-based antidepressants: 20 years on

    Trends Pharmacol. Sci.

    (2009)
  • B. Szewczyk et al.

    The involvement of serotonergic system in the antidepressant effect of zinc in the forced swim test

    Prog. Neuropsychopharmacol. Biol. Psychiatry

    (2009)
  • A. Takeda et al.

    Insight into zinc signaling from dietary zinc deficiency

    Brain Res. Rev.

    (2009)
  • N.M. Tassabehji et al.

    Zinc deficiency induces depression-like symptoms in adult rats

    Physiol. Behav.

    (2008)
  • R. Amani et al.

    Correlation between dietary zinc intakes and its serum levels with depression scales in young female students

    Biol. Trace Elem. Res.

    (2010)
  • A.D. Basterzi et al.

    IL-6 levels decrease with SSRI treatment in patients with major depression

    Hum. Psychopharmacol.

    (2005)
  • K. Cieslik et al.

    Influence of zinc supplementation on imipramine effect in a chronic unpredictable stress (CUS) model in rats

    Pharmacol. Rep.

    (2007)
  • Cited by (105)

    View all citing articles on Scopus
    View full text