Study of the Serum Copper Levels in Patients with Major Depressive Disorder

Biological Trace Element Research, May 2016

Copper may be involved in the pathophysiology of depression. Clinical data on this issue are very limited and not conclusive. The purpose of the study was to determine the copper concentration in the serum of patients with major depressive disorder and to discuss its potential clinical usefulness as a biomarker of the disease. A case–control clinical study included 69 patients with current depressive episode, 45 patients in remission and 50 healthy volunteers. Cu concentration was measured by electrothermal atomic absorption spectrometry (ETAAS). The mean serum copper level in depressed patients was slightly lower (by 11 %; not statistically significant) than in the control group. Furthermore, there was no significant difference in Cu2+ concentration between depressive episode and remission, nor between remission and control group. In the remission group were observed significant correlations between copper levels and the average number of relapses over the past years or time of remission. There was no correlation between serum copper and severity of depression, as measured by HDRS and MADRS. The obtained results showed no significant differences between the copper concentration in the blood serum of patients (both with current depressive episode and in remission) and healthy volunteers, as well as the lack of correlations between the copper level in the active stage of the disease and clinical features of the population. Our study is the first conducted on such a large population of patients, so the results may be particularly important and reliable source of knowledge about the potential role of copper in depression.

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Study of the Serum Copper Levels in Patients with Major Depressive Disorder

Biol Trace Elem Res Study of the Serum Copper Levels in Patients with Major Depressive Disorder Krzysztof Styczeń 0 1 2 3 4 5 Magdalena Sowa-Kućma 0 1 2 3 4 5 Marcin Siwek 0 1 2 3 4 5 Dominika Dudek 0 1 2 3 4 5 Witold Reczyński 0 1 2 3 4 5 Paulina Misztak 0 1 2 3 4 5 Bernadeta Szewczyk 0 1 2 3 4 5 Roman Topór-Mądry 0 1 2 3 4 5 Włodzimierz Opoka 0 1 2 3 4 5 Gabriel Nowak 0 1 2 3 4 5 0 Department of Analytical Chemistry, University of Science and Technology , Kraków , Poland 1 Department of Neurobiology, Laboratory of Trace Elements Neurobiology, Institute of Pharmacology PAS , Kraków , Poland 2 Department of Affective Disorders, Chair of Psychiatry, Jagiellonian University Medical College , Kraków , Poland 3 Department of Inorganic and Analytical Chemistry, Jagiellonian University Medical College , Kraków , Poland 4 Department of Epidemiology and Population Studies, Institute of Public Health, Jagiellonian University Medical College , Kraków , Poland 5 Department of Pharmacobiology, Jagiellonian University Medical College , Kraków , Poland Copper may be involved in the pathophysiology of depression. Clinical data on this issue are very limited and not conclusive. The purpose of the study was to determine the copper concentration in the serum of patients with major depressive disorder and to discuss its potential clinical usefulness as a biomarker of the disease. A case-control clinical study included 69 patients with current depressive episode, 45 patients in remission and 50 healthy volunteers. Cu concentration was measured by electrothermal atomic absorption spectrometry (ETAAS). The mean serum copper level in depressed patients was slightly lower (by 11 %; not statistically significant) than in the control group. Furthermore, there was no significant difference in Cu2+ concentration between depressive episode and remission, nor between remission and control group. In the remission group were observed significant correlations between copper levels and the average number of relapses over the past years or time of remission. There was no correlation between serum copper and severity of depression, as measured by HDRS and MADRS. The obtained results showed no significant differences between the copper concentration in the blood serum of patients (both with current depressive episode and in remission) and healthy volunteers, as well as the lack of correlations between the copper level in the active stage of the disease and clinical features of the population. Our study is the first conducted on such a large population of patients, so the results may be particularly important and reliable source of knowledge about the potential role of copper in depression. Copper; Depression; Biomarkers; Affective disorders; Unipolar depression; MDD - Krzysztof Styczeń and Magdalena Sowa-Kućma contributed equally to this work. Introduction * Copper (Cu) is the third most abundant trace metal (behind iron and zinc) present in every tissue and is required for essential body functions. As a cofactor for numerous enzymes, it plays an important role in the biochemical processes, including erythropoiesis, cellular respiration, peptide amidation, iron, cholesterol and glucose metabolism, pigment formation, and hormones biosynthesis (see [ 1 ] for review). These metal ions are also necessary for the proper development and functioning of the central nervous system; low copper level may result in incomplete development, while excess concentration maybe injurious [ 2 ]. Among the body organs, the brain is the one of the most copper-rich (next to the heart and liver) [ 3 ]. The total human body contains only 75–100 mg, and the recommended daily dosage for adult men and women is 0.9 mg/day (1–1.3 mg/day for pregnant or lactating women). Copper is relatively a stable component of the blood, and its concentration usually remains between 100 and 130 mg/100 ml of the serum [ 4, 5 ]. Approximately 90 % of the copper in the blood is incorporated into ceruloplasmin, which is responsible for carrying copper to tissues that need the mineral [ 6, 7 ]. Proper absorption and metabolism of copper requires an appropriate balance with the minerals zinc and manganese. Because zinc can compete with copper in the small intestine and interfere with its absorption, persons who supplement with inappropriately high levels of zinc and lower levels of copper may increase their risk of copper deficiency [ 8 ]. That is why the plasma/ serum ratio of copper to zinc (optimal 0.70–1.00) is clinically more important than the blood concentration of either of these trace metals. A crucial role in maintaining proper cellular zinc and copper concentration play metallothioneins, which have the capacity to bind both these ions through the thiol group of its cysteine residues. In the human body, large quantities are synthesized primarily in the liver and kidneys and their production is dependent on availability of the dietary minerals [ 8 ]. Coppe (...truncated)


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Krzysztof Styczeń, Magdalena Sowa-Kućma, Marcin Siwek, Dominika Dudek, Witold Reczyński, Paulina Misztak, Bernadeta Szewczyk, Roman Topór-Mądry, Włodzimierz Opoka, Gabriel Nowak. Study of the Serum Copper Levels in Patients with Major Depressive Disorder, Biological Trace Element Research, 2016, pp. 287-293, Volume 174, Issue 2, DOI: 10.1007/s12011-016-0720-5