Philippe Bovier

Relationship between erythrocyte magnesium, plasma electrolytes and cortisol, and intensity of symptoms in major depressed patients

53 male and female drug-free major depressed patients were separated into three groups according to the severity of the depression. In the entire regrouped population, plasma and erythrocyte magnesium (Mg) were shown to increase as compared with 48 healthy controls, confirming our previous studies. The middle and highly depressed patients had higher erythrocyte and also plasma Mg levels than either lowly depressed patients or controls. Only, a few differences were noticed in plasma sodium, potassium and calcium (Ca) in the three groups of patients, except for ultrafiltrable plasma Ca, measured for the first time in affective disorders. Thus, erythrocyte and also plasma Mg are shown to be associated with the intensity of the depression. As blood hypomagnaesemia is often related to hyperexcitability, further investigations are actually in process to shown whether hypermagnesaemia might be, in contrast, associated with psychomotor retardation as observed in many depressed patients.

The decrease of erythrocyte catechol-O-methyltransferase activity in depressed patients and its diagnostic significance.

ABSTRACT: Erythrocyte catechol‐O‐methyltransferase (COMT) activity was measured in normal and depressed populations before specific medication. In the groups of patients, anxiety and depression scores were evaluated by the AMDP rating scale. The authors found lower enzyme activity in patients with major depression, recurrent and bipolar disorder, depressed, but no change was found in dysthymic disorder when compared to control values. However, there was no relationship between COMT activity and age, anxiety and depression scores of patients. Furthermore, the subdivision into two subpopulations, one with normal COMT activity and another with lower COMT activity, did not make it possible to assign a role to the enzyme in the severity of depression. The enzyme could, however, be considered as a genetic marker of depressive vulnerability.

Evolution of blood magnesium, sodium and potassium in depressed patients followed for three months.

No consensus has been obtained about blood electrolyte status, especially about magnesium, in affective disorders. This is mainly due to the lack of information about the distribution of the patients in clinical subgroups, sex, type of treatment and about the severity of their illnesses. Most of these studies concerned treated patients. We confirmed in this study that drug-free depressed patients have higher erythrocyte and plasma magnesium than controls, as shown in previous reports. Significant differences are observed in as shown in previous reports. Significant differences are observed in patients for sex and between clinical subgroups. Low plasma potassium levels are described in both male and female depressed patients. The erythrocyte magnesium level tends to normalize in parallel with clinical improvement, depending on sex and clinical subgroup, and seems then to be related to the intensity of the depression. Plasma magnesium in male and female patients, except for female unipolars, remains higher than controls in all conditions and might be related to the diagnosis of affective disorders.

The effect of clinical outcome on platelet G proteins of major depressed patients

Platelet G protein subunits (G alpha i2, G alpha q and Gbeta) were measured in 15 non-treated depressed patients (recurrent major depression) and 15 age- and sex-matched healthy controls by using the Western immunoblot method. The depression severity was measured by the AMDP depression rating scale before start of treatment. The AMDP score ranged between 12 and 44. Patients were then treated with different antidepressant drugs (ATD) for 1 month, after which G protein and depression were reassessed. Results indicated that drug-free depressed patients displayed increased levels of G proteins subunits, in comparison to healthy controls. Antidepressant drug administration resulted in decrease of depression severity but only seven patients showed a net response to drugs (AMDP depression score less than 12). These drug-responding patients have also reduced G protein levels, while patients without significant improvement continued to display either the same levels of G proteins or higher, whatever the class of the drug administered. These results suggest that depression is associated to increase in G protein subunit levels and that the clinical outcome seemed to be the determining factor in further decrease occurring in G protein levels.

Platelet membrane alpha2-adrenergic receptors in depression

The platelet membrane was used as a model system to examine alpha 2-adrenergic receptors in 30 depressed patients and 30 healthy control subjects. The number of binding sites and their affinity for 3H-UK 14304 (5-bromo-6-(2-imidazoline-2-ylamino)-quinoxaline), a potent, highly selective alpha 2-adrenergic receptor agonist, was measured. Plasma magnesium and free 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations were assayed in the same sample. A decreased agonist-receptor affinity was found in depressed patients, whereas receptor density was not significantly altered compared with that in control subjects. In bipolar depressed and dysthymic patients, there was a tendency toward a higher density of alpha 2-adrenergic receptors. This trend was not apparent in unipolar, recurrent depressed subjects. Moreover, a positive correlation between Bmax and Kd values was observed in patients but not in control subjects--a finding that suggests that a compensatory phenomenon occurs in depression. After the patients were treated with antidepressant drugs, an increased affinity (decrease in Kd) was observed, together with a decrease in binding sites. Plasma magnesium concentrations were higher in drug-free depressed patients than in control subjects. In addition, magnesium concentrations were negatively correlated with the density of alpha 2-adrenergic receptor binding sites in depressed patients, both before and during treatment. Lastly, a trend toward a negative correlation between plasma MHPG concentration and the number of binding sites was also observed. These results suggest a complex multifactorial regulation of alpha 2-adrenergic receptors, which are probably hyposensitive in depressive syndromes.

Adrenaline-Induced Platelet Aggregation in Depressed Patients and Control Subjects

We measured alpha 2-adrenoceptor-mediated platelet primary aggregation in depressed patients and healthy subjects. Both initial velocity and maximum amplitudes of platelet response to increasing concentrations of adrenaline were decreased in drug-free depressed patients as compared with controls. The EC50 of both initial slope and maximum amplitude were also increased in drug-free depressed patients. The results suggested a lowered platelet alpha 2-adrenoceptor function. Demographic factors (age and sex) and the time between blood collection and start of aggregation monitoring did not influence the results. This report is consistent with postsynaptic receptor desensitization in depressed patients. The precise molecular mechanism for this impairment remains to be elucidated.

Reversible in vitro Decrease of L-Tyrosine and L-Tryptophan Influx across the Human Erythrocyte Membrane Induced by Cytochalasin B, the Specific Inhibitor of D-Glucose Transport

For many years, we have been studying, in psychiatric conditions, the influx of tyrosine (TYR) and tryptophan (TRP), the two amino acid precursors of monoamines, across the membrane of human blood cells. We have also attempted to characterize better the transport mechanisms. In a previous paper, we suggested a close relationship between glucose and the two neuter amino acid transports in vitro. The purpose of the present study is to test the effect of cytochalasin B, the specific and potent inhibitor of glucose transport. Our data show that at high concentrations, the cytochalasin B induces a reversible inhibition of about 70% or more on the temperature-dependent influx of the two amino acids, depending on the medium of incubation. The effect of cytochalasin B was about 200 times less for TYR and TRP transport than for glucose. The cytochalasin E, claimed to be a nonspecific inhibitor, decreased both these transports only when used at very high concentrations, as described for sugar influx in the same structure. In conclusion, we suggest that there is a relationship between the transport of glucose and nucleosides, both carried into the cells by the glycoprotein band 4.5, and the two amino acid precursors of monoamines.

Weak association between blood sodium, potassium, and calcium and intensity of symptoms in major depressed patients

In previous reports, we showed that plasma and erythrocyte magnesium were increased in many drug-free hospitalized depressed patients. Furthermore, we observed that erythrocyte magnesium content was related to the intensity of the symptoms. Highly depressed patients had the highest magnesium values. Today, we report the results of plasma and erythrocyte sodium and potassium, and of total and ultrafilterable plasma calcium in 66 hospitalized patients with major depression compared to 58 healthy controls. No consistent differences in these biochemical parameters are observed between patients when separated according to intensity of anxiety, psychomotor retardation, and moral distress. Plasma sodium is higher and plasma potassium lower in female patients of all subgroups as compared to controls. Both male patients and controls have erythrocyte sodium and potassium levels that are significantly different from those of females. This clearly suggests a separation into genders in such studies. In conclusion--in contrast to blood magnesium--sodium, potassium, and calcium levels do not seem to be related to the intensity of the main clinical symptoms in hospitalized patients with major depression.

Decrease in Epinephrine-lnduced Attenuation of Platelet Adenylate Cyclase Activity in Depressed Patients: Relation with Plasma Electrolytes

We have measured the alpha 2-adrenoceptor-mediated inhibition of platelet membrane adenylate cyclase in depressed patients and control subjects. The results showed a decrease in the forskolin-stimulated adenylate cyclase inhibition of depressed patients compared to the healthy subjects. This suggests a subsensitivity of alpha 2-adrenoceptor in depression. However, this subsensitivity was not correlated to the severity of depression as both severely and moderately depressed patients exhibited the same percent of adenylate cyclase inhibition. The antidepressant drugs treatment induced an increase in the percent of adenylate cyclase inhibition with a trend towards the control values. However, this increase did not equal control value, and moreover both remitted and unremitted patients presented a similar change in their alpha 2-adrenoceptor-mediated adenylate cyclase inhibition. This result raises the question about a simple and direct relation between the clinical status of depression and the power of alpha 2-adrenoceptor-mediated adenylate cyclase inhibition. Plasma magnesium and sodium yielded correlations to this alpha 2-adrenoceptor-mediated adenylate cyclase inhibition suggesting a relation between the platelet adrenergic function and plasma electrolytes.

Evolution of Red Blood Cell Membrane Transport and Plasma Level of L-Tyrosine and L-Tryptophan in Depressed Treated Patients According to Clinical Improvement

The erythrocyte membrane transport (MT) of L-tyrosine (TYR) and L-tryptophan (TRP) and their plasma concentration showed abnormal mean values in 37 depressed patients compared to control subjects before treatment. The pattern of these abnormal values differed according to the clinical subgroup (DSM III criteria). In bipolar disorders the TYR values were all low and the TRP values showed little change, except a low level of plasma TRP. In major depression, MT were abnormal (MT TYR low, MT TRP high) with a very low plasma TRP. In dysthymic disorders the TYR and TRP values were normal. The normalization of the above biochemical variables was significantly correlated with the clinical improvement; however, the plasma concentration of TRP remained abnormal in some patients who had recovered. In contrast, only plasma TYR and TRP were significantly increased in patients without recovery.