G. J. Naylor

Vanadium: a possible aetiological factor in manic depressive illness.

The effect of Vitamin C in manic-depressive psychosis was assessed by a double-blind, placebo controlled, crossover trial. Both manic and depressed patients were significantly better following a single 3 g dose of Vitamin C than following a placebo. Preliminary results of a double-blind, crossover comparison of normal vanadium intake with reduced intake in manic and depressed subjects are reported. Both manic and depressed patients were significantly better on reduced intake. These results are in keeping with the suggestion that vanadium may be an aetiological factor in manic depressive illness.

Erythrocyte membrane cation carrier in manic-depressive psychosis

Erythrocyte Na-K ATPase and sodium pump site numbers were estimated in groups of depressed, manic and recovered patients. The activity of Na-K ATPase per pump site was lower in the depressed group than in the recovered group. In the manic group Na-K ATPase was lower than that of the recovered group, whereas there was no difference in the pump site numbers. In the more severe manics the activity of Na-K ATPase per pump site was significantly lower than that of the recovered patients. Therefore, the change occurring in the erythrocyte membrane cation carrier in manic-depressive psychosis is probably in the activity of individual Na-K ATPase molecules and not in the number of Na-K ATPase molecules per cell.

Lithium therapy and erythrocyte membrane cation carrier

Plasma cortisol and erythrocyte Na-K ATPase, ouabain sensitive K+ influx, lithium, sodium and potassium concentrations were measured twice when patients were on placebo and twice when they were on lithium therapy. The erythrocyte Na-K ATPase was significantly higher during the lithium than during the placebo treated period, whereas the other biochemical values measured showed no significant difference between the two phases.

A double-blind, placebo controlled, crossover trial of carbamazepine in overactive, severely mentally handicapped patients

A double-blind, placebo controlled, crossover trial of carbamazepine in 12 severely and profoundly mentally retarded, overactive adult patients is described. The trial lasted 7 months and those patients in whom overactivity was the dominant problem responded to some degree to carbamazepine with a reduction in overactivity. This was particularly so in patients in whom overactivity was accompanied by some elevation of mood. Patients in whom overactivity was part of a wider spectrum of multiple behaviour disorders showed a scatter of responses. There was no relationship between response to carbamazepine and the presence or absence of epilepsy. The trial identified a small group of mentally retarded patients in whom carbamazepine might be clinically useful.

Erythrocyte membrane cation carrier in mania.

Erythrocyte sodium and potassium concentrations, erythrocyte membrane ATPase (Na-K specific and non-specific) and the rate of potassium influx into erythrocytes (ouabain-sensitive and insensitive) were estimated in a group of female patients suffering from mania and repeated on about two thirds of them when they had recovered. With recovery there was a statistically significant increase in the erythrocyte ouabain-sensitive potassium influx. The other parameters showed no significant overall change with recovery but the initial severity correlated significantly and negatively with the change in erythrocyte Na-K ATPase with recovery. The changes that occurred in the erythorcyte sodium concentration and Na-K ATPase activity were not random since they correlated significantly with changes in the active potassium influx.

Plasma vanadium concentration in manic-depressive illness.

133 samples of plasma taken from 9 normal control and 8 manic-depressive subjects were analysed for vanadium by atomic absorption spectrometry. Mean plasma vanadium concentrations were 0 . 15 microM in normal control, 0 . 34 microM in manic and 0 . 28 microM in depressed subjects, and 0 . 23 microM in manic-depressive subjects after recovery. The differences between normal subjects and manic and recovered subjects were statistically significant. Significant negative correlations were found between plasma vanadium concentration and the ratio of Na-K-Mg ATPase to Mg-ATPase in 2 manic-depressive subjects, but not in normal subjects. The results suggest that vanadium may be a cause of the variations in Na-K-Mg ATPase and sodium pump activity which are associated with manic-depressive illness.

Erythrocyte membrane cation carrier, relapse rate of manic-depressive illness and response to lithium.

Biochemical studies of manic-depressive psychosis usually correlates biochemical findings with current affective state and hence any significant findings could be secondary to mood change. The present study attempts to correlate measures of the erythrocyte membrane cation carrier with clinical events, remote in time from the biochemical assay. Eprythrocyte sodium concentration, ouabain-sensitive potassium influx and Na-K ATPase were estimated in 11 patients before and after the cross-over point in a 2-year double blind clinical trial ratio tended to suffer most episodes of affective illness in the 2 years. Patients who had a low initial Na-K ATPase or a high initial flux sodium ATPase ratio, or in whom this ratio fell most with lithium or whose Na-K ATPase rose most with lithium, clinically responded best to lithium.

Pharmacokinetic aspects of protriptyline plasma levels

SummaryPlasma levels of protriptyline have been determined in 30 depressed female patients undergoing antidepressant therapy. After 3 1/2 weeks treatment at dosage levels of 40 mg/day, protriptyline plasma levels ranged from 430 to 1430 nmol/l. During this period only two-thirds of the subjects had definitely achieved asymptotic concentrations. Single dose studies in 5 volunteers suggest that the volume of distribution of protriptyline shows little intersubject variation. The half life of the drug, however, may vary appreciably from subject to subject, ranging from 54 to 198 h. The effects of two sedatives on mean protriptyline plasma levels have been determined. Mean plasma levels for nitrazepam recipients are indistinguishable from those for patients receiving no night sedation. The mean plasma levels for a group of patients receiving sodium amylobarbitone were significantly reduced. The problem of choice and early adjustment of dosages in order to achieve satisfactory plasma levels is discussed. For practical purposes it is suggested that early values may be of predictive significance in allowing early dosage adjustments to be made.

Lithium and erythrocyte membrane cation carrier studies in normal and manic depressive subjects.

Changes in the erythrocyte membrane cation carrier following lithium ingestion in normal human subjects were studied; ouabain sensitive potassium influx fell significantly during the lithium treated phase. Lithium was fed to rats and no change in erythrocyte Na-K ATPase was shown. These findings contrast with studies of lithium in manic depressive psychosis. The fluctuations in the erythrocyte membrane cation carrier were studied in 5 normal subjects over 12 weeks and the correlations between the parameters calculated. The erythrocyte sodium concentration correlated positively with the ouabain sensitive potassium influx. This too contrasts with findings in manic depressive psychosis.

Tissue vanadium levels in manic-depressive psychosis

The vanadium content of hair, whole blood, serum and urine was estimated by neutron activation analysis in samples from manic patients, depressed patients, recovered manic patients, recovered depressed patients and normal controls. The results suggest that manic patients have significantly raised vanadium levels in hair which fall towards control levels with recovery, but there are no significant differences in the mean vanadium content of whole blood or serum. In contrast, depressed patients have raised levels of vanadium in whole blood and serum which appear to fall with recovery. Levels of vanadium in serum correlate strongly with those in whole blood, but neither shows significant correlation with vanadium in hair for either patients or controls. Hair and blood probably serve as indicator tissues for differing aspects of vanadium metabolism.