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Journal of the American College of Nutrition, Vol. 23, No. 5, 549S-551S (2004)
Published by the American College of Nutrition

The Influence of Some Antipsychotics on Erythrocyte Magnesium and Plasma Magnesium, Calcium, Copper and Zinc in Patients with Paranoid Schizophrenia

Mihai Nechifor, C. Vaideanu, I. Palamaru, C. Borza and I. Mindreci

Department of Pharmacology (M.N., C.V.), University of Medicine and Pharmacy "Gr. T. Popa" Iasi, ROMANIA
Institute of Hygiene Public Health (P.I.), University of Medicine and Pharmacy "Gr. T. Popa" Iasi, ROMANIA
Department of Psychiatry (C.B.), University of Medicine and Pharmacy "Gr. T. Popa" Iasi, ROMANIA
Department of Biophysics (I.M.), University of Medicine and Pharmacy "Gr. T. Popa" Iasi, ROMANIA

Address reprint requests to: Nechifor Mihai, Department of Pharmacology, University of Medicine and Pharmacy, "Gr. T. Popa" Iasi, Str. Universita'tii nr. 16, Iasi, 700115, ROMANIA. E-mail: mnechif{at}iasi.mednet.ro


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 CONCLUSIONS
 REFERENCES
 
Objective: The aim of the study was the investigation of plasma magnesium, calcium, copper and zinc and erythrocyte magnesium levels in patients with paranoid schizophrenia and the influence of the therapy with two antipsychotic drugs (haloperidol and risperidone) on these concentrations.

Methods: We investigated the influence of treatment with haloperidol and risperidoneon plasma and erythrocyte magnesium and on plasmatic levels of zinc, calcium and copper on hospitalized 56 patients diagnosed with paranoid schizophrenia (DSM IV).

Results: Our data indicate a decrease of erythrocyte magnesium levels in schizophrenic patients (4.82 ± 3.1 mg/L vs. 59.2 ± 1.1 mg/L in control group, p < 0.01). The plasma level of magnesium was unchanged (18.9 ± 2.17 mg/L in schizophrenic patients vs. 18.26 ± 1.9 mg/L in control group).

Conclusions: We consider plasma Cu2+/erythrocyte Mg2+ and plasma Cu2+/Zn2+ ratio two important biological markers of the acute paranoid schizophrenia.

Key words: erythrocyte Mg, plasma Mg, plasma Ca, Cu, Zn, paranoid schizophrenia, antipsychotic drugs, haloperidol, risperidone


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 CONCLUSIONS
 REFERENCES
 
Magnesium (Mg) and other bivalent cations play many roles in the normal functions of the central nervous system. Plasma and erythrocyte Mg levels are altered in different psychiatric disorders: major depression [1,2], schizophrenia, pharmacodependence [3], etc. There are also changes of copper (Cu) and zinc (Zn) in these disorders. There are few available on the influence of antipsychotic therapy on concentrations of these cations and about the possible correlations between the clinical state under antipsychotic therapy and plasma levels of Mg or other bivalent cations. This study investigated plasma Mg, Ca, Cu and Zn erythrocyte Mg levels in patients with paranoid schizophrenia and the influence of the therapy with two antipsychotic drugs (haloperidol and risperidone) on these concentrations.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 CONCLUSIONS
 REFERENCES
 
The studied group consisted of 56 patients (32 women and 24 men, aged between 18–65 years, median of 38 years) diagnosed with paranoid schizophrenia (DSM IV), who were hospitalized in the Clinical Hospital of Psychiatry "Socola" Iasi, in 2002–2003. All the patients were in an acute psychotic episode of schizophrenia, and had not received antipsychotic therapy before being admitted to the hospital. We investigated the influence of treatment with haloperidol (Haldol®) and risperidone (Rispolept®) on plasma and erythrocyte Mg and on plasmatic levels of Ca, Zn, and Cu.

The patients were divided in two groups:

Patients included in the study had been hospitalized for at least 4 weeks, and been treated with one of the antipsychotic drugs for at least 3 weeks. Concentrations of these cations were also determined in a control group of 20 healthy volunteers, of the same age and gender as the studied group of schizophrenic patients. Excluded from the study were alcoholic patients, cirrhotic patients, those with chronic renal failure or who had been treated before with antipsychotic drugs, diuretics, cations, or patients with chronic diarrhea or vomiting. All patients were comparably fed during hospitalization.

Cations concentrations were determined spectrophotometrically, and the obtained data were statistically interpreted. The research respected the general rules of clinical studies.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
CONCLUSIONS
 REFERENCES
 
Plasma and erythrocyte Mg concentrations are indicated in Fig. 1.



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  		Fig. 1. The influence of haloperidol and risperidone on blood plasma and erythrocyte magnesium level in paranoid schizophrenia patients. *p < 0.01 vs. schizophrenia level before treatment. **p < 0.05 vs. schizophrenia level before treatment. NS = non significant vs. schizophrenia level before treatment.

 
The variations of plasma Zn, Cu, and Ca concentrations in schizophrenic patients and the influence of the therapy with haloperidol or risperidone are indicated in Table 1.


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  		Table 1. Haloperidol and Risoperidone Influence in Calcium, Zinc and Copper Levels in Adult Patients with Paranoid Schizophrenia

 

   DISCUSSION
 
The pathogenesis of schizophrenia, and the molecular mechanism(s) involved, are only partially elucidated. Differences have been reported in blood plasma and cellular concentrations of Mg in schizophrenic patients. Some authors [4,5] found high Mg level in blood plasma and cerebrospinal fluid (CSF). Others found decreased Mg2+ plasma level and CSF concentrations in schizophrenia [6–9]. The heterogeneity of the data is due both to heterogeneity of patients and because there are many forms of schizophrenia. Our data indicate lower erythrocyte Mg levels in schizophrenic patients (4.82 ± 3.1 mg/L) than in the control group (5.92 ± 1.1 mg/L, p < 0.01). The plasma level of Mg does not differ in schizophrenic patients (18.9 ± 2.17 mg/L) from values in the control group (18.26 ± 1.9 mg/L).

There are few data on the influence of drugs used in treatment of different psychoses on bivalent cations concentrations. The drugs used in schizophrenia therapy can be classified as typical antipsychotic and atypical antipsychotic drugs. Haloperidol (a classic neuroleptic drug) is a strong blocker of D1, D2 and {alpha}1 receptor and a weak blocker of 5 HT2A receptors. Risperidone (an atypical antipsychotic drug) is a strong blocker of D2, 5HTA2A and H1 receptors, but has a very low activity on the level of D1 receptors.

The haloperidol effect on Mg2+ level is controversial. Jabotinski-Rubin et al. [10], showed a decreased effect of haloperidol on Mg2+ plasma level in schizophrenic patients. Our data showed that haloperidol and risperidone do not significantly modify the plasma magnesium level, but enhance the erythrocyte Mg concentration, with the haloperidol effect being stronger. The mechanism of this effect is still unclear. Our results are comparable to the findings of Levine et al. [7].

We believe that the increase of Mg cell level is important for antipsychotic action of haloperidol and risperidone.

The effect of Mg could be produced by:

There are many data showing that the plasma level of Cu is increased in schizophrenic patients [11,12]. The elevated cell and plasma Cu level is involved in psychotic behaviour in patients with Wilson disease [13]. Manser et al. [14] found a high concentration of both Cu and lead in patients with schizophrenia. We found no significant difference of plasma Cu in schizophrenic patients (906 ± 32 µg/L) than in the control group (1130 ± 53 µg/L) (NS). Neither haloperidol nor risperidone change the Cu plasma level after 3 weeks of treatment.

Zinc plays a very complex role in the brain. Andrews et al. [15] support the Zn deficiency theory in the pathogenesis of schizophrenia. Pfeiffer and Ilier [12] showed a lower plasma Zn level and a Cur excess in schizophrenic patients. Adams et al. [16] indicated a loss of Zn in the hippocampus of schizophrenic patients. Our data show a low plasma Zn in paranoid schizophrenic patients before treatment (0.60 ± 0.09 mg/L vs. 0.89 ± 0.12 mg/L in healthy controls, p < 0.01). Haloperidol and risperidone increase Zn levels in plasma (1.06 ± 0.4 mg/L after haloperidol and 0.1 ± 0.1 mg/L after risperidone, p < 0.01).


   CONCLUSIONS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 CONCLUSIONS
REFERENCES
 
The ratio between plasma Cu2+ and erythrocyte Mg2+ level, and also the ratio between Cu and Zn plasma levels, are increased in patients with acute paranoid schizophrenia episode. Erythrocyte and plasma Mg levels and Zn plasma level are decreased in an acute attack of paranoid schizophrenia. Haloperidol and risperidone enhance both erythrocyte Mg and plasma Zn levels, but do not change plasma Mg concentration. We consider plasma Cu2+/erythrocyte Mg2+ and plasma Cu2+/Zn2+ ratio two important biological markers of the acute paranoid schizophrenia.

Received August 5, 2004.
   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 CONCLUSIONS
 REFERENCES
 

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  5. Gattaz WF, Kattermann R, Gattaz D, Beckmann H: Magnesium and calcium in the CSF of schizophrenic patients and healthy controls: correlations with cyclic group.Biol Psychiatry18 :935 –939,1983 .[Medline]
  6. Yassa R, Nair NP, Schwartz G: Plasma magnesium in chronic schizophrenia. A preliminary report.In. Pharmacopsychiatr ,14 :57 –64,1979 .
  7. Levine J, Rappaport A, Mashiah M, Dolev E: Serum and cerebrospinal levels of calcium and magnesium in acute versus remitted schizophrenic patients.Neuropsychobiology33 :169 –172,1996 .[Medline]
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  10. Jabotinsky-Rubin K, Durst R, Levitin LA, Moscovich DG, Silver H, Lerner J, Van Praag H, Gardner EL: Effects of haloperidol on human plasma magnesium.J Psychiatr Res27 :155 –159,1993 .
  11. Olantunbosun DA, Akindele BK, Adadevoh BK, Asuni T: Serum copper in schizophrenia in Nigerians.Br J Psychiatry27 :119 –121,1975 .
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  14. Manser WW, Khan MD, Hassan Z: Blood copper, zinc, magnesium and lead level in psychiatric patients with disturbed behaviour.J Pak Med Assoc39 :235 –338,1989 .[Medline]
  15. Andrews RC: Unification of the findings in schizophrenia by reference to the effects of gestational zinc deficiency.J Med Hypotheses31 :141 –153,1990 .
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