Plasma and erythrocyte electrolytes in affective disorders.

Plasma and erythrocyte sodium (Na+), total and free (ultrafiltrable) plasma magnesium (Mg2+) as well as erythrocyte magnesium were measured in patients with affective disorders and in healthy control subjects. Depressed and manic patients had higher total plasma Mg2+ than did hospitalized healthy control subjects, but concentrations of ultrafiltrable Mg2+ did not differ. Although erythrocyte Mg2+ was significantly elevated in the depressed subjects in comparison with that found in the non-hospitalized healthy controls, this difference was not seen between the depressives and the hospitalized healthy controls. Depressed, manic or healthy control subjects did not differ with respect to either plasma or erythrocyte.

Lithium and the kidney: a review.

The effects of lithium on renal water and electrolyte transport have generally been considered to be reversible following the cessation of lithium treatment. However, several recent reports have suggested that lithium-induced nephrogenic diabetes insipidus may persist for months or even years after lithium is discontinued. In addition, a number of reports have described the development of renal insufficiency (in association with interstitial nephritis) in some patients who have been chronically treated with lithium. The authors briefly review the effects of lithium on renal tubular transport and critically examine the reports of lithium-induced renal disease.

Cerebral evoked potential changes produced by treatment with lithium carbonate.

To confirm and extend previous findings concerning evoked potential (EP) changes produced by lithium carbonate (Li), 12 depressive patients were studied while on placebo and on therapeutic doses of Li. Four kinds of EPs were recorded from 14 leads: somatosensory (SEP) to left (LSEP) and right (RSEP) median nerve stimuli; visual (VEP) to a checkerboard flash; auditory (AEP) to binaural click. Plasma and erythrocyte (RBC) Li levels and Hamilton Depression ratings were obtained. Li produced a number of amplitude changes in EPs of all sensory modalities, while there were few latency changes; in general, amplitudes of positive components were increased, while negative component amplitudes were reduced. The spatial distributions of EP peaks were mainly unaltered by Li. The amount of EP amplitude change with Li tended to be correlated with plasma and RBC Li levels. No convincing correlations were found between alterations in EPs and depression ratings. The nature of the EP changes with Li was generally not concordant with normalization of the deviant EP characteristics found in depressives. The findings indicate that Li produces more widespread CNS changes than suggested by previous reports; it appears that these tend to be related to Li levels, but not to the therapeutic effects of Li.

MMPI prediction of imipramine response: a replication study.

18 hospitalized male depressives were treated with imipramine hydrochloride for 28 days. Prior to initiating treatment, each patient completed the Minnesota Multiphasic Personality Inventory (MMPI). At the end of the treatment period, the patients were divided into groups of responders and nonresponders based on the change in their Hamilton Depression Rating Scale scores. The Imipramine Response Scale - Male (IRS-M) was scored for each patient and the ability of the scale to predict response or nonresponse in our sample of patients was examined. There was no evidence that the IRS-M was better than chance in its ability to predict response.

Biological component of the NIMH clinical research branch collaborative program on the psychobiology of depression: II. Methodology and data analysis.

A preceding paper has reviewed the history, background, and rationale for this collaborative effort exploring the biologic basis of the affective disorders. This paper details the "flow" of a subject through the experimental protocol, the instrumentation used to obtain the clinical and behavioural data, and the biologic methodologies employed in the analysis of the body fluids. Data management and analysis techniques developed for this study are also examined.

Prediction of dosage of lithium carbonate: use of a standard predictive method.

The nomogram developed by Cooper and associates used to predict the dose of Lithium Carbonate (Li+) which is needed to attain therapeutic Li+ concentrations has, in general, proven to be accurate and clinically useful. However, there may be some patients in whom the pharmacokinetic disposition of Li+ varies sufficiently so that accurate dosage predictions cannot be made; a report of one such patient is given.

The erythrocyte lithium-plasma lithium ratio in patients with primary affective disorder.

Increasing attention has been given to the significance of intra-cellular concentrations of the lithium ion in patients treated with this drug. The erythrocyte has been the most common cell investigated because of its accessibility and certain similarities between the ion transport mechanisms of this cell and the neuron. Intraerythrocyte lithium is expressed as the ratio of lithium in the cell to the plasma lithium concentration (lithium ratio). The lithium ratio has been reported to be related to a number of clinical variables, including treatment response, clinical state, side-effects, toxicity, diagnosis, and electrophysiological effects. We have investigated the lithium ratio in a large series of patients with a primary affective disorder and in a smaller control group. We found a significantly higher mean lithium ratio in the bipolar diagnostic group than in the unipolar and control groups. There was a trend, not statistically significant, in the unipolar and bipolar groups for females to have higher lithium ratios than males. While not diagnostic, the lithium ratio appears to be another biological variable where bipolar patients, as a group, differ from normals and others with an affective disorder.

Plasma and erythrocyte cations in affective illness.

Plasma and erythrocyte cations (sodium and magnesium) were studied in groups of patients with an affective disorder and in normal subjects. Baseline determinations were obtained before initiation of treatment for mania or depression. In a subgroup of patients, sequential measurements of cations were made during treatment with lithium carbonate. No differences were found in intraerythrocyte sodium or magnesium among any of the patient groups and controls. Patients with a primary affective disorder had significantly higher plasma sodium than control subjects. Neither baseline cation concentrations nor changes in cation concentration during treatment with lithium correlated with treatment response. Gender was shown to be a significant variable affecting intraerythrocyte cation concentrations.

Erythrocyte concentrations of the lithium ion: clinical correlates and mechanisms of action.

When lithium carbonate is administered to individuals, there is considerable intersubject variation in the extent of accumulation of Li+ by erythrocytes. The primary reason for this is differences in the activity of a Li+-Na+ counterflow system, which, under clinical conditions, removes Li+ from the cell. It appears that some bipolar patients accumulate more Li+ in their red cells than either unipolar depressives or normal controls. The precise clinical characteristics of the bipolar patients who accumulate relatively large amounts of erythrocyte Li+ need to be clarified in future research. Finally, the measurement of red cell concentrations of Li+, in addition to the usual plasma measurement, can be used as an indicator of patient compliance.

Red blood cell Li+ to plasma Li+ ratios. Are they related to plasma Li+ concentrations?

The relationship between the lithium ratio (ratio of lithium in blood cells to that in plasma) and plasma lithium concentration was examined in a group of male inpatients taking lithium carbonate for affective disorders. The lithium ratio was found to increase in the majority of these patients as plasma lithium concentration increased. However, the magnitude of variation of the lithium ratio with plasma lithium concentration observed in these patients is not sufficient to seriously affect the value of determining the lithium ratio in the clinical situation.

Prediction of the lithium ratio in man by means of an in vitro test.

The movement of the lithium ion (Li+) across the membrane of intact erythrocytes incubated in vitro was assessed under two different experimental conditions in which such transfer occurred primarily due to the activity of a lithium-sodium countertransport system. The 13 subjects on whom the in vitro procedures were done subsequently received lithium carbonate for 14 to 56 days, and the extent of accumulation of Li+ by erythrocytes in vivo was measured. While both in vitro procedures yielded data that correlated with the extent of accumulation of Li+ by erythrocytes in vivo, a system measuring the efflux of Li+ from Li+-loaded cells produced a much higher correlation (0.976). The magnitude of this correlation suggests that this in vitro system can be used for further investigations into the relevance of the erythrocyte accumulation of Li+ to the pathogenesis and treatment of affective disorders.