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Kamkar M Z, Siamaki Khaboshan F, Marjani A. Comparison of Serum Zinc Levels between Patients with Schizophrenia and Healthy Individuals. jcbr 2020; 4 (3) :34-39
URL: http://jcbr.goums.ac.ir/article-1-273-en.html
URL: http://jcbr.goums.ac.ir/article-1-273-en.html
1- Golestan Research Center of Psychiatry, Golestan University of Medical Sciences, Gorgan, Iran
2- Department of Biochemistry and Biophysics, Metabolic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran
2- Department of Biochemistry and Biophysics, Metabolic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran
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Abstract
Background and objectives: Schizophrenia is a debilitating mental disorder characterized by disruptions in thought processes, perceptions, emotional responsiveness, and social interactions. Zinc is a neuroactive element released in synapses during neuronal activity and is required for proper functioning of the nervous system, particularly the brain. Serum and tissue concentrations of zinc may reflect various physiological and pathophysiological conditions. Evidence suggests a link between zinc level and development of schizophrenia. The aim of this study was to compare serum zinc levels between patients with schizophrenia and healthy individuals.
Methods: This case-control study was performed on 55 patients (37 men and 18 women) with schizophrenia who were hospitalized in 5 Azar Hospital in Gorgan (Iran) and 55 healthy individuals. The case subjects were selected based on convenience sampling method using the Positive and Negative Syndrome Scale (PANSS), while the control subjects were enrolled based on the General Health Questionnaire-28 (GHQ-28). The groups were matched in terms of age and gender. Serum concentration of zinc was measured using a commercial colorimetric assay kit (5-Br-PAPS method).
Results: Serum zinc concentration did not differ significantly between the patients and the controls (P=0.93). In schizophrenic patients, there was a significant, negative correlation between age and serum zinc concentration (r=-0.298, P=0.027). In both patients and controls, serum zinc level was significantly higher in men than in women (P<0.05).
Conclusion: Based on the results, it is recommended to pay more attention to the diet of patients with schizophrenia.
Keywords: Zinc; Schizophrenia; Trace elements; Mental disorder
DISCUSSION
In the present study, the mean age of male and female patients was 36.81 and 42.94 years, respectively. Previous studies have also shown that men develop schizophrenia at a younger age compared to women (5).
We found no significant difference in the serum zinc levels between the patients and healthy subjects, which is consistent with findings of some previous studies (19, 20). However, in a meta-analysis by Joe et al., serum zinc levels in schizophrenics were lower than in the healthy individuals. In the mentioned study, serum zinc levels of patients treated with antipsychotics did not differ significantly from those of healthy individuals (16). However, it should be noted that the mentioned study was performed on schizophrenics under treatment with antipsychotics, while we enrolled newly diagnosed or non-treated patients. It has been reported that newly diagnosed schizophrenics generally have lower serum zinc levels than healthy people (17), but we observed no such difference in our study. Because schizophrenia is a heterogeneous disorder, not all patients are expected to have a serum zinc abnormality as part of the syndrome, which may explain the conflicting results of different studies. In a study by Chen et al., at time of admission, schizophrenic patients had lower serum zinc levels compared to healthy controls, which is inconsistent with our findings. They also
reported that serum zinc levels were inversely correlated with the age of patients, which is in line with our findings (5). The inverse correlation between age and serum zinc levels might be due to the age-related downexpression of membrane zinc transporter genes (24).
It has been well-established that zinc has a vital role in the proper functioning of physiological systems, such as the nervous system. Convergence of clinical, molecular and genetic data plays a major role for zinc homeostasis in relation to depression and mental disorders. Intracellular zinc deficiency as well as circulating zinc deficiency may be due to poor diet or impaired absorption related to aging or a medical condition, such as alcoholism. Various medications including anticonvulsants, diabetes medications, hormones, anti-acids and anti-inflammatory drugs that are commonly prescribed to patients with neurological disorders also affect zinc absorption. In addition, genetic zinc transporter defects can affect zinc concentrations. Clinical studies have indicated the beneficial effects of zinc supplementation in relieving depression, which signifies the importance of investigating the effectiveness of zinc as a potential treatment option for mental illnesses (17).
CONCLUSION
The results of the present study showed that the mean serum concentration of zinc does not differ significantly between schizophrenic patients and healthy individuals. In both patients and controls, serum zinc level is significantly higher in men than in women. Moreover, serum zinc level has a significant, negative correlation with age in schizophrenics. Based on the results, it is recommended to pay more attention to the diet of patients with schizophrenia.
ACKNOWLEDGEMENTS
The authors would like to thank all participants and the staff of Golestan University of Medical Sciences and psychiatric ward of 5 Azar hospital, especially the esteemed head nurse Mr. Alireza Nikjoo, who helped us in this research. This article has been derived from PhD thesis of Ms. Fatemeh Siamaki Khaboshan.
DECLARATIONS
Funding
This research project has been supported by the Golestan University of Medical sciences, Iran.
Ethics approvals and consent to participate
The study has been approved by the ethics committee of the Golestan University of Medical sciences, Iran (ethics code: IR.GOUMS.REC.1398.249). Written consent was obtained from all participants.
Conflict of interest
The author declares that there is no conflict of interest regarding publication of this article.
REFERENCES
1. Takeda A, Tamano H. Insight into zinc signaling from dietary zinc deficiency. Brain research reviews. 2009; 62(1):33-44. DOI:
10.1016/j.brainresrev.2009.09.003. Source. PubMed.
2. Hanafi I, Arafat S, Al Zayed L, Sukkar M, Albeirakdar A, Krayem D, Essali A. Haloperidol (route of administration) for people with schizophrenia. Cochrane Systematic Review - Intervention - Protocol Version published: 19 October 017.https://doi.org/10.1002/14651858.CD01283.
3.Mössner R, Schuhmacher A, Wagner M, Lennertz L. Steinbrecher A, Quednow BB, Rujescu D, Rietschel M, Maier W. The schizophrenia risk gene ZNF804A influences the antipsychotic response of positive schizophrenia symptoms. European archives of psychiatry and clinical neuroscience. 2011; 262(3):193-7.
https://doi.org/10.1007/s00406-011-0235-1
40 David CN, Greenstein D, Clasen L, Gochman P, Miller R, Tossell JW,et al. Childhood onset schizophrenia: High rate of visual hallucinations. J Am Acad Child Adolesc Psychiatry.2011;50(7):681-6.
https://doi.org/10.1016/j.jaac.2011.03.020
5. Ochoa S, Usall J, Cobo J, Labad X, Kulkarni J. Gender Differences in Schizophrenia and First-Episode Psychosis: A Comprehensive Literature Review. Schizophr Res Treatment. 2012;2012: 916198 doi: 10.1155/2012/916198
6. Meaney AM, O'Keane V. Reduced bone mineral density in patients with schizophrenia receiving prolactin raising anti-psychotic medication. J Psychopharmacol. 2003;17(4):455-8.
https://doi.org/10.1177/0269881103174011
7. Crespo-Facorro B, Barbadillo L, Pelayo-Terán JM, Rodríguez-Sánchez JM. Neuropsychological functioning and brain structure in schizophrenia. International Review of Psychiatry. 2007; 19(4):325-36.
https://doi.org/10.1080/09540260701486647
8. Howard L, Kirkwood G, Leese M. Risk of hip fracture in patients with a history of schizophrenia. The British Journal of Psychiatry. 2007;190(2):129-134.
https://doi.org/10.1192/bjp.bp.106.023671
9. Szczotka J, Majchrowicz B. Schizophrenia as a disorder of embodied self. Psychiatr Pol. 2018;52(2):199-215.
https://doi.org/10.12740/PP/67276
10. Farzin D, Mansouri NA, Yazdani T, EBRAHIMI P, ZARGHAMI M, AZARI P, et al. Elevated plasma copper/zinc ratios in patients with schizophrenia. 2007;9(1):14-9.
11. Grønli O, Kvamme JM, Friborg O, Wynn R. Zinc deficiency is common in several psychiatric disorders. PLoS One. 2013;8(12).
https://doi.org/10.1371/journal.pone.0082793
12. Ghanem AA, Ali EM, El-Bakary A, El-Morsy D, Elkanishi S, Saleh E-S, et al. Copper and Zinc Levels in Hair of Both Schizophrenic and Depressed Patients. Mansoura J Forensic Med Clin Toxicol. 2009;17(1):89-102.
https://doi.org/10.21608/mjfmct.2009.53299
13. King JC. Zinc: an essential but elusive nutrient. Am J Clin Nutr. 2011 Aug
https://doi.org/10.3945/ajcn.110.005744
94(2): 679S-684S. Published online 2011 Jun 29. doi: 10.3945/ajcn.110.005744.
14. Chasapis CT, Loutsidou AC, Spiliopoulou CA, Stefanidou ME. Zinc and human health: an update. November 2011Archives of Toxicology 86(4):521-34. Follow journal.DOI: 10.1007/s00204-011-0775-1. Source. PubMed.
https://doi.org/10.1007/s00204-011-0775-1
15. Lichten LA, Ryu MS, Guo L, Embury J, Cousins RJ. MTF-1-mediated repression of the Zinc transporter Zip10 is alleviated by Zinc restriction. https://doi.org/10.1371/journal.pone.0021526.
16. Joe P, Petrilli M, Malaspina D, Weissman J. Zinc in schizophrenia: a meta-analysis. Gen Hosp Psychiatry. 2018;53:19-24.
https://doi.org/10.1016/j.genhosppsych.2018.04.004
17. Petrilli MA, Kranz TM, Kleinhaus K, Joe P, Getz M, Johnson P, Chao MV, Malaspina D. The emerging role for zinc in depression and psychosis. Front. Pharmacol. 30 June 2017 | https://doi.org/10.3389/fphar.2017.00414.
18. Craven C, Duggan PF, Buckley N, Gaughran F. Serum zinc levels in patients with schizophrenia and their mothers. Schizophrenia research. 1997; 26(1):83-4.
https://doi.org/10.1016/S0920-9964(97)00039-X
19. Yanik M, Kocyigit A, Tutkun H, Vural H, Herken H. Plasma manganese, selenium, zinc,
copper, and iron concentrations in patients with schizophrenia. Biol Trace Elem Res. 2004;98(2):109-17.
https://doi.org/10.1385/BTER:98:2:109
20. Vidović B, Crossed D Signorcrossed D Signević B, Milovanović SDS, Škrivanj S, Pavlović Z, Stefanović A, et al. Selenium, zinc, and copper plasma levels in patients with schizophrenia: relationship with metabolic risk factors. Biol Trace Elem Res. 2013;156(1-3):22-8. https://doi.org/10.1007/s12011-013-9842-1
21. Cai L, Chen T, Yang J, Zhou K, Yan X, Chen W, et al. Serum trace element differences between Schizophrenia patients and controls in the Han Chinese population. Sci Rep. 2015;5:15013.
https://doi.org/10.1038/srep15013
22. Chen X, Li Y, Zhang T, Yao Y, Shen C, Xue Y. Association of Serum Trace Elements with Schizophrenia and Effects of Antipsychotic Treatment. Biol Trace Elem Res. 2018;181(1):22-30.
https://doi.org/10.1007/s12011-017-1039-6
23 Hjelle EG, Bragstad LK, Zucknick M, Kirkevold M, Thommessen B, Sveen U. The General Health Questionnaire-28 (GHQ-28) as an outcome measurement in a randomized controlled trial in a Norwegian stroke population. BMC Psychol 7, 18 (2019). https://doi.org/10.1186/s40359-019-0293-0
24. Olesen RH, Hyde TM, Kleinman JE, Smidt K, Rungby J, Larsen A. Obesity and age-related alterations in the gene expression of zinc-transporter proteins in the human brain. Transl Psychiatry.2016;6(6):e838. doi:10.1038/tp.2016.83.
How to Cite: Kamkar M Z, Siamaki Khaboshan F, Marjani A. Comparison of Serum Zinc Levels between Patients with Schizophrenia and Healthy Individuals. jcbr. 2020; 4 (3)
Background and objectives: Schizophrenia is a debilitating mental disorder characterized by disruptions in thought processes, perceptions, emotional responsiveness, and social interactions. Zinc is a neuroactive element released in synapses during neuronal activity and is required for proper functioning of the nervous system, particularly the brain. Serum and tissue concentrations of zinc may reflect various physiological and pathophysiological conditions. Evidence suggests a link between zinc level and development of schizophrenia. The aim of this study was to compare serum zinc levels between patients with schizophrenia and healthy individuals.
Methods: This case-control study was performed on 55 patients (37 men and 18 women) with schizophrenia who were hospitalized in 5 Azar Hospital in Gorgan (Iran) and 55 healthy individuals. The case subjects were selected based on convenience sampling method using the Positive and Negative Syndrome Scale (PANSS), while the control subjects were enrolled based on the General Health Questionnaire-28 (GHQ-28). The groups were matched in terms of age and gender. Serum concentration of zinc was measured using a commercial colorimetric assay kit (5-Br-PAPS method).
Results: Serum zinc concentration did not differ significantly between the patients and the controls (P=0.93). In schizophrenic patients, there was a significant, negative correlation between age and serum zinc concentration (r=-0.298, P=0.027). In both patients and controls, serum zinc level was significantly higher in men than in women (P<0.05).
Conclusion: Based on the results, it is recommended to pay more attention to the diet of patients with schizophrenia.
Keywords: Zinc; Schizophrenia; Trace elements; Mental disorder
INTRODUCTION
Schizophrenia is a debilitating, long-term mental disorder that leads to misconceptions, inappropriate actions and deviations from reality due to disturbed connections between thoughts, feelings and behaviors (1). The etiology of schizophrenia is multifactorial, involving the interaction of genetic and environmental factors (2). Recently, a gene called ZNF804A has been implicated in schizophrenia. Strong body of evidence suggests that this gene is functionally linked to schizophrenia and may be considered a new target for therapeutic intervention (3). The age of disease onset is between 18 and 25 years in men and between 25 and 35 years in women. It affects both genders to the same extent, but men show symptoms of the disease at a younger age than women do (4-6).
Cerebral atrophy has been implicated in established schizophrenia, which is associated with cognitive dysfunction (7). In animal models of schizophrenia, hippocampal lesions are expanded, leading to frontal lobe aneurysm rupture (9). Zinc is a neuroactive element released at synapses during neuronal activity. Serum and tissue concentrations of zinc may reflect various physiological and pathological conditions. The recommended daily intake of zinc varies from person to person but is usually 15 mg in men and 12 mg in women (10). This trace element is essential for the proper functioning of the human body, especially the brain. The highest concentrations of zinc are found in the hippocampus and amygdala (11).
Although a link between zinc level and schizophrenia has been suggested (1), research findings on the status of trace elements in patients with schizophrenia have been controversial. A study reported a significant increase in serum copper and hair copper concentrations and a significant decrease in zinc level in schizophrenics compared to healthy controls (12). Cells in the salivary glands, prostate, immune system and intestines utilize zinc signals to
communicate with other cells. In the brain, zinc is stored in specific synaptic vesicles by glutamatric neurons and can modulate brain excitability, affecting synaptic plasticity and cognition. Zinc homeostasis also plays an important role in the normal functioning of the brain and central nervous system (13). Zinc deficiency increases copper concentrations, which can increase anxiety, irritability and emotional instability (14, 15). The role of zinc has been implicated in depressive disorders, but the possible association of zinc with schizophrenia has not been sufficiently studied (16). Although studies on zinc supplementation for the treatment of schizophrenia have been somewhat promising, further studies are required to understand the disease and to improve treatment methods (17). As mentioned earlier, results of studies on the level of zinc and other trace elements in patients with schizophrenia have been contradictory (18-21). A meta-analysis in 2018 reported that serum zinc levels are notably lower in patients with schizophrenia than in healthy individuals (16). Another study claimed that there is a relationship between low serum zinc levels and high-risk and abnormal behaviors in patients with schizophrenia (22). In a study on the relationship of trace elements with schizophrenia and the effects of antipsychotics therapy, serum zinc concentrations were lower after risperidone therapy. The mentioned studies also reported that the patients had significantly higher concentration of magnesium and phosphorus and significantly lower concentrations of iron, calcium and zinc compared to healthy controls. Age was positively correlated with iron and copper concentrations and negatively correlated with calcium, phosphorus and zinc concentrations in the control group (23). In this study, we aimed to compare the level of serum zinc in patients with schizophrenia and healthy individuals.
MATERIALS AND METHODS
This was a case-control study that included 55 patients (37 men and 18 women) with schizophrenia who were admitted to the psychiatric ward of 5 Azar Hospital in Gorgan, Iran. The control group consisted of 55 healthy persons accompanying patients referred to the hospital. The groups were matched in terms of age, gender and ethnicity. Written consent was obtained from all individuals. The sample size was estimated based on the study of Chen et al. using the G.Power application and considering type I error of 5% (α) and test power of 95% (β) (22). The patients were selected based on convenience sampling method using the Positive and Negative Syndrome Scale (PANSS), while the control subjects were enrolled based on the General Health Questionnaire-28 (GHQ-28) (23).
The patients were either not receiving any medication or had stopped taking their medication for at least a year. Inclusion criteria were confirmed diagnosis of schizophrenia by a psychiatrist according to the DSM-5 criteria, hospitalization in the psychiatric ward of the hospital, age of 20 to 55 years and discontinuation of medication for at least one year. Exclusion criteria were presence of any other mental illnesses, having autoimmune, cardiovascular, hepatic, renal and allergic diseases, pregnancy, a history of drug abuse and consumption of medications that affect the metabolism of zinc i.e. tetracycline, fluoroquinolones, bisphosphonates, some anticonvulsants, contraceptives and glucocorticoid. Fasting blood samples (3 ml) were taken between 7 and 9 am. Next, serum was separated and stored at -80 oC. Serum concentration of zinc was measured using a commercial colorimetric assay kit (5-Br-PAPS method).
Statistical analysis of data was carried out using the SPSS 16 software package. Demographic and laboratory data were analyzed using descriptive statistics. Normality of data was assessed by the
Shapiro-Wilk test. The independent t-test and Mann-Whitney non-parametric test were used to compare serum zinc levels between the study groups for normally and not normally distributed data, respectively. The Pearson correlation test was used to evaluate the association between variables. All statistical analyses were performed at significance of 0.05.
RESULTS
The mean age of male patients was 36.81 ± 10.86 years and the mean age of female patients was 42.94 ± 10.15 years. The mean age of patients and controls were 38.82 ± 10.93 and 39 ± 10.70, respectively. In terms of ethnicity, the case group included 35 Persians (63.6%), 8 Turkmen (16.4%) and 11 Baluchis (20%).
The serum concentration of zinc did not differ significantly between the patients (76.87 ± 15.43 μg/dl) and healthy controls (76.42±22.05 μg/dl) (P=0.93). Based on the results of the independent t-test, serum concentrations of zinc were significantly higher in men than in women in both study groups (Table 1).
Cerebral atrophy has been implicated in established schizophrenia, which is associated with cognitive dysfunction (7). In animal models of schizophrenia, hippocampal lesions are expanded, leading to frontal lobe aneurysm rupture (9). Zinc is a neuroactive element released at synapses during neuronal activity. Serum and tissue concentrations of zinc may reflect various physiological and pathological conditions. The recommended daily intake of zinc varies from person to person but is usually 15 mg in men and 12 mg in women (10). This trace element is essential for the proper functioning of the human body, especially the brain. The highest concentrations of zinc are found in the hippocampus and amygdala (11).
Although a link between zinc level and schizophrenia has been suggested (1), research findings on the status of trace elements in patients with schizophrenia have been controversial. A study reported a significant increase in serum copper and hair copper concentrations and a significant decrease in zinc level in schizophrenics compared to healthy controls (12). Cells in the salivary glands, prostate, immune system and intestines utilize zinc signals to
communicate with other cells. In the brain, zinc is stored in specific synaptic vesicles by glutamatric neurons and can modulate brain excitability, affecting synaptic plasticity and cognition. Zinc homeostasis also plays an important role in the normal functioning of the brain and central nervous system (13). Zinc deficiency increases copper concentrations, which can increase anxiety, irritability and emotional instability (14, 15). The role of zinc has been implicated in depressive disorders, but the possible association of zinc with schizophrenia has not been sufficiently studied (16). Although studies on zinc supplementation for the treatment of schizophrenia have been somewhat promising, further studies are required to understand the disease and to improve treatment methods (17). As mentioned earlier, results of studies on the level of zinc and other trace elements in patients with schizophrenia have been contradictory (18-21). A meta-analysis in 2018 reported that serum zinc levels are notably lower in patients with schizophrenia than in healthy individuals (16). Another study claimed that there is a relationship between low serum zinc levels and high-risk and abnormal behaviors in patients with schizophrenia (22). In a study on the relationship of trace elements with schizophrenia and the effects of antipsychotics therapy, serum zinc concentrations were lower after risperidone therapy. The mentioned studies also reported that the patients had significantly higher concentration of magnesium and phosphorus and significantly lower concentrations of iron, calcium and zinc compared to healthy controls. Age was positively correlated with iron and copper concentrations and negatively correlated with calcium, phosphorus and zinc concentrations in the control group (23). In this study, we aimed to compare the level of serum zinc in patients with schizophrenia and healthy individuals.
MATERIALS AND METHODS
This was a case-control study that included 55 patients (37 men and 18 women) with schizophrenia who were admitted to the psychiatric ward of 5 Azar Hospital in Gorgan, Iran. The control group consisted of 55 healthy persons accompanying patients referred to the hospital. The groups were matched in terms of age, gender and ethnicity. Written consent was obtained from all individuals. The sample size was estimated based on the study of Chen et al. using the G.Power application and considering type I error of 5% (α) and test power of 95% (β) (22). The patients were selected based on convenience sampling method using the Positive and Negative Syndrome Scale (PANSS), while the control subjects were enrolled based on the General Health Questionnaire-28 (GHQ-28) (23).
The patients were either not receiving any medication or had stopped taking their medication for at least a year. Inclusion criteria were confirmed diagnosis of schizophrenia by a psychiatrist according to the DSM-5 criteria, hospitalization in the psychiatric ward of the hospital, age of 20 to 55 years and discontinuation of medication for at least one year. Exclusion criteria were presence of any other mental illnesses, having autoimmune, cardiovascular, hepatic, renal and allergic diseases, pregnancy, a history of drug abuse and consumption of medications that affect the metabolism of zinc i.e. tetracycline, fluoroquinolones, bisphosphonates, some anticonvulsants, contraceptives and glucocorticoid. Fasting blood samples (3 ml) were taken between 7 and 9 am. Next, serum was separated and stored at -80 oC. Serum concentration of zinc was measured using a commercial colorimetric assay kit (5-Br-PAPS method).
Statistical analysis of data was carried out using the SPSS 16 software package. Demographic and laboratory data were analyzed using descriptive statistics. Normality of data was assessed by the
Shapiro-Wilk test. The independent t-test and Mann-Whitney non-parametric test were used to compare serum zinc levels between the study groups for normally and not normally distributed data, respectively. The Pearson correlation test was used to evaluate the association between variables. All statistical analyses were performed at significance of 0.05.
RESULTS
The mean age of male patients was 36.81 ± 10.86 years and the mean age of female patients was 42.94 ± 10.15 years. The mean age of patients and controls were 38.82 ± 10.93 and 39 ± 10.70, respectively. In terms of ethnicity, the case group included 35 Persians (63.6%), 8 Turkmen (16.4%) and 11 Baluchis (20%).
The serum concentration of zinc did not differ significantly between the patients (76.87 ± 15.43 μg/dl) and healthy controls (76.42±22.05 μg/dl) (P=0.93). Based on the results of the independent t-test, serum concentrations of zinc were significantly higher in men than in women in both study groups (Table 1).
Table 1. Comparison of serum zinc levels between patients with schizophrenia and healthy controls based on gender
| Group | Serum zinc level (mean ± standard deviation) | P-value | |
| Men | Women | ||
| Patients | 79.92±13.27 μg/dl | 70.61±17.94 μg/dl | 0.035 |
| Control | 80.49±21.60 μg/dl | 68.06±21.13 μg/dl | 0.049 |
The serum concentration of zinc did not differ significantly between the three ethnic groups of patients (P=0.16). There was no significant correlation between age and serum concentration of zinc (r=-0.16, P=0.08). However, there was a significant negative correlation between age and serum zinc level in the patients (r=-0.22, P=0.02).
DISCUSSION
In the present study, the mean age of male and female patients was 36.81 and 42.94 years, respectively. Previous studies have also shown that men develop schizophrenia at a younger age compared to women (5).
We found no significant difference in the serum zinc levels between the patients and healthy subjects, which is consistent with findings of some previous studies (19, 20). However, in a meta-analysis by Joe et al., serum zinc levels in schizophrenics were lower than in the healthy individuals. In the mentioned study, serum zinc levels of patients treated with antipsychotics did not differ significantly from those of healthy individuals (16). However, it should be noted that the mentioned study was performed on schizophrenics under treatment with antipsychotics, while we enrolled newly diagnosed or non-treated patients. It has been reported that newly diagnosed schizophrenics generally have lower serum zinc levels than healthy people (17), but we observed no such difference in our study. Because schizophrenia is a heterogeneous disorder, not all patients are expected to have a serum zinc abnormality as part of the syndrome, which may explain the conflicting results of different studies. In a study by Chen et al., at time of admission, schizophrenic patients had lower serum zinc levels compared to healthy controls, which is inconsistent with our findings. They also
reported that serum zinc levels were inversely correlated with the age of patients, which is in line with our findings (5). The inverse correlation between age and serum zinc levels might be due to the age-related downexpression of membrane zinc transporter genes (24).
It has been well-established that zinc has a vital role in the proper functioning of physiological systems, such as the nervous system. Convergence of clinical, molecular and genetic data plays a major role for zinc homeostasis in relation to depression and mental disorders. Intracellular zinc deficiency as well as circulating zinc deficiency may be due to poor diet or impaired absorption related to aging or a medical condition, such as alcoholism. Various medications including anticonvulsants, diabetes medications, hormones, anti-acids and anti-inflammatory drugs that are commonly prescribed to patients with neurological disorders also affect zinc absorption. In addition, genetic zinc transporter defects can affect zinc concentrations. Clinical studies have indicated the beneficial effects of zinc supplementation in relieving depression, which signifies the importance of investigating the effectiveness of zinc as a potential treatment option for mental illnesses (17).
CONCLUSION
The results of the present study showed that the mean serum concentration of zinc does not differ significantly between schizophrenic patients and healthy individuals. In both patients and controls, serum zinc level is significantly higher in men than in women. Moreover, serum zinc level has a significant, negative correlation with age in schizophrenics. Based on the results, it is recommended to pay more attention to the diet of patients with schizophrenia.
ACKNOWLEDGEMENTS
The authors would like to thank all participants and the staff of Golestan University of Medical Sciences and psychiatric ward of 5 Azar hospital, especially the esteemed head nurse Mr. Alireza Nikjoo, who helped us in this research. This article has been derived from PhD thesis of Ms. Fatemeh Siamaki Khaboshan.
DECLARATIONS
Funding
This research project has been supported by the Golestan University of Medical sciences, Iran.
Ethics approvals and consent to participate
The study has been approved by the ethics committee of the Golestan University of Medical sciences, Iran (ethics code: IR.GOUMS.REC.1398.249). Written consent was obtained from all participants.
Conflict of interest
The author declares that there is no conflict of interest regarding publication of this article.
REFERENCES
1. Takeda A, Tamano H. Insight into zinc signaling from dietary zinc deficiency. Brain research reviews. 2009; 62(1):33-44. DOI:
10.1016/j.brainresrev.2009.09.003. Source. PubMed.
2. Hanafi I, Arafat S, Al Zayed L, Sukkar M, Albeirakdar A, Krayem D, Essali A. Haloperidol (route of administration) for people with schizophrenia. Cochrane Systematic Review - Intervention - Protocol Version published: 19 October 017.https://doi.org/10.1002/14651858.CD01283.
3.Mössner R, Schuhmacher A, Wagner M, Lennertz L. Steinbrecher A, Quednow BB, Rujescu D, Rietschel M, Maier W. The schizophrenia risk gene ZNF804A influences the antipsychotic response of positive schizophrenia symptoms. European archives of psychiatry and clinical neuroscience. 2011; 262(3):193-7.
https://doi.org/10.1007/s00406-011-0235-1
40 David CN, Greenstein D, Clasen L, Gochman P, Miller R, Tossell JW,et al. Childhood onset schizophrenia: High rate of visual hallucinations. J Am Acad Child Adolesc Psychiatry.2011;50(7):681-6.
https://doi.org/10.1016/j.jaac.2011.03.020
5. Ochoa S, Usall J, Cobo J, Labad X, Kulkarni J. Gender Differences in Schizophrenia and First-Episode Psychosis: A Comprehensive Literature Review. Schizophr Res Treatment. 2012;2012: 916198 doi: 10.1155/2012/916198
6. Meaney AM, O'Keane V. Reduced bone mineral density in patients with schizophrenia receiving prolactin raising anti-psychotic medication. J Psychopharmacol. 2003;17(4):455-8.
https://doi.org/10.1177/0269881103174011
7. Crespo-Facorro B, Barbadillo L, Pelayo-Terán JM, Rodríguez-Sánchez JM. Neuropsychological functioning and brain structure in schizophrenia. International Review of Psychiatry. 2007; 19(4):325-36.
https://doi.org/10.1080/09540260701486647
8. Howard L, Kirkwood G, Leese M. Risk of hip fracture in patients with a history of schizophrenia. The British Journal of Psychiatry. 2007;190(2):129-134.
https://doi.org/10.1192/bjp.bp.106.023671
9. Szczotka J, Majchrowicz B. Schizophrenia as a disorder of embodied self. Psychiatr Pol. 2018;52(2):199-215.
https://doi.org/10.12740/PP/67276
10. Farzin D, Mansouri NA, Yazdani T, EBRAHIMI P, ZARGHAMI M, AZARI P, et al. Elevated plasma copper/zinc ratios in patients with schizophrenia. 2007;9(1):14-9.
11. Grønli O, Kvamme JM, Friborg O, Wynn R. Zinc deficiency is common in several psychiatric disorders. PLoS One. 2013;8(12).
https://doi.org/10.1371/journal.pone.0082793
12. Ghanem AA, Ali EM, El-Bakary A, El-Morsy D, Elkanishi S, Saleh E-S, et al. Copper and Zinc Levels in Hair of Both Schizophrenic and Depressed Patients. Mansoura J Forensic Med Clin Toxicol. 2009;17(1):89-102.
https://doi.org/10.21608/mjfmct.2009.53299
13. King JC. Zinc: an essential but elusive nutrient. Am J Clin Nutr. 2011 Aug
https://doi.org/10.3945/ajcn.110.005744
94(2): 679S-684S. Published online 2011 Jun 29. doi: 10.3945/ajcn.110.005744.
14. Chasapis CT, Loutsidou AC, Spiliopoulou CA, Stefanidou ME. Zinc and human health: an update. November 2011Archives of Toxicology 86(4):521-34. Follow journal.DOI: 10.1007/s00204-011-0775-1. Source. PubMed.
https://doi.org/10.1007/s00204-011-0775-1
15. Lichten LA, Ryu MS, Guo L, Embury J, Cousins RJ. MTF-1-mediated repression of the Zinc transporter Zip10 is alleviated by Zinc restriction. https://doi.org/10.1371/journal.pone.0021526.
16. Joe P, Petrilli M, Malaspina D, Weissman J. Zinc in schizophrenia: a meta-analysis. Gen Hosp Psychiatry. 2018;53:19-24.
https://doi.org/10.1016/j.genhosppsych.2018.04.004
17. Petrilli MA, Kranz TM, Kleinhaus K, Joe P, Getz M, Johnson P, Chao MV, Malaspina D. The emerging role for zinc in depression and psychosis. Front. Pharmacol. 30 June 2017 | https://doi.org/10.3389/fphar.2017.00414.
18. Craven C, Duggan PF, Buckley N, Gaughran F. Serum zinc levels in patients with schizophrenia and their mothers. Schizophrenia research. 1997; 26(1):83-4.
https://doi.org/10.1016/S0920-9964(97)00039-X
19. Yanik M, Kocyigit A, Tutkun H, Vural H, Herken H. Plasma manganese, selenium, zinc,
copper, and iron concentrations in patients with schizophrenia. Biol Trace Elem Res. 2004;98(2):109-17.
https://doi.org/10.1385/BTER:98:2:109
20. Vidović B, Crossed D Signorcrossed D Signević B, Milovanović SDS, Škrivanj S, Pavlović Z, Stefanović A, et al. Selenium, zinc, and copper plasma levels in patients with schizophrenia: relationship with metabolic risk factors. Biol Trace Elem Res. 2013;156(1-3):22-8. https://doi.org/10.1007/s12011-013-9842-1
21. Cai L, Chen T, Yang J, Zhou K, Yan X, Chen W, et al. Serum trace element differences between Schizophrenia patients and controls in the Han Chinese population. Sci Rep. 2015;5:15013.
https://doi.org/10.1038/srep15013
22. Chen X, Li Y, Zhang T, Yao Y, Shen C, Xue Y. Association of Serum Trace Elements with Schizophrenia and Effects of Antipsychotic Treatment. Biol Trace Elem Res. 2018;181(1):22-30.
https://doi.org/10.1007/s12011-017-1039-6
23 Hjelle EG, Bragstad LK, Zucknick M, Kirkevold M, Thommessen B, Sveen U. The General Health Questionnaire-28 (GHQ-28) as an outcome measurement in a randomized controlled trial in a Norwegian stroke population. BMC Psychol 7, 18 (2019). https://doi.org/10.1186/s40359-019-0293-0
24. Olesen RH, Hyde TM, Kleinman JE, Smidt K, Rungby J, Larsen A. Obesity and age-related alterations in the gene expression of zinc-transporter proteins in the human brain. Transl Psychiatry.2016;6(6):e838. doi:10.1038/tp.2016.83.
How to Cite: Kamkar M Z, Siamaki Khaboshan F, Marjani A. Comparison of Serum Zinc Levels between Patients with Schizophrenia and Healthy Individuals. jcbr. 2020; 4 (3)
Article Type: Research |
Subject:
Basic medical sciences
References
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17. Petrilli MA, Kranz TM, Kleinhaus K, Joe P, Getz M, Johnson P, Chao MV, Malaspina D. The emerging role for zinc in depression and psychosis. Front. Pharmacol. 30 June 2017 | [View at Publisher] [DOI] [PubMed] [Google Scholar]
18. Craven C, Duggan PF, Buckley N, Gaughran F. Serum zinc levels in patients with schizophrenia and their mothers. Schizophrenia research. 1997; 26(1):83-4. [View at Publisher] [DOI] [PubMed] [Google Scholar]
19. Yanik M, Kocyigit A, Tutkun H, Vural H, Herken H. Plasma manganese, selenium, zinc,
copper, and iron concentrations in patients with schizophrenia. Biol Trace Elem Res. 2004;98(2):109-17. [View at Publisher] [DOI] [PubMed] [Google Scholar]
20. Vidović B, Crossed D Signorcrossed D Signević B, Milovanović SDS, Škrivanj S, Pavlović Z, Stefanović A, et al. Selenium, zinc, and copper plasma levels in patients with schizophrenia: relationship with metabolic risk factors. Biol Trace Elem Res. 2013;156(1-3):22-8. [View at Publisher] [DOI] [PubMed] [Google Scholar]
21. Cai L, Chen T, Yang J, Zhou K, Yan X, Chen W, et al. Serum trace element differences between Schizophrenia patients and controls in the Han Chinese population. Sci Rep. 2015;5:15013. [View at Publisher] [DOI] [PubMed] [Google Scholar]
22. Chen X, Li Y, Zhang T, Yao Y, Shen C, Xue Y. Association of Serum Trace Elements with Schizophrenia and Effects of Antipsychotic Treatment. Biol Trace Elem Res. 2018;181(1):22-30. [View at Publisher] [DOI] [PubMed] [Google Scholar]
23. 23 Hjelle EG, Bragstad LK, Zucknick M, Kirkevold M, Thommessen B, Sveen U. The General Health Questionnaire-28 (GHQ-28) as an outcome measurement in a randomized controlled trial in a Norwegian stroke population. BMC Psychol 7, 18 (2019). [View at Publisher] [DOI] [PubMed] [Google Scholar]
24. Olesen RH, Hyde TM, Kleinman JE, Smidt K, Rungby J, Larsen A. Obesity and age-related alterations in the gene expression of zinc-transporter proteins in the human brain. Transl Psychiatry.2016;6(6):e838. doi:10.1038/tp.2016.83. [View at Publisher] [PubMed] [Google Scholar]
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