Lithium treatment of aggressive children and the EEG.

Electroencephalograms (EEG-s) of 44 children aged 6.3--15.4 years were examined at the baseline and 3 months later with two different doses of lithium. Lithium levels in serum in group I. ranged from 0.08 mmol/l to 0.33 mmol/l (mean: 0.23 mmol/l SD: 0.105), and in group II. ranged from 0.40 mmol/l to 0.84 mmol/l (mean: 0.555 mmol/l SD: 0.116). These children represent as Conduct Disorder. EEG-s were correlated across treatment groups with behavioural ratings, ratings of untoward effects, reaction time and different dosages of medication. In the group I. alpha-recovery time after-eye closing and percentage time of alpha activity in 60 s decreased at unchanged mean alpha frequency. In the group II. both alpha recovery time and alpha activity increased at unchanged mean alpha frequency. Paroxysmal focal abnormalities (spikes, spike-waves etc.) or increase in percentage time of delta activity were not found. Behavioural changes were assessed by using the Pictures Frustration Test for Children of Rosenzweig and the Hamburg Personality Inventory for Children. The group II. were found to be significantly superior to group I. in decreasing aggressive symptoms. No serious differences were found for the reaction time and side effects as well.

Therapeutic experience with lithium in childhood aggressivity.

An account is given of the therapeutic experience with lithium in childhood hyperaggressivity. In 13 cases of the hospitalized 17 children between 3 and 12 years of age significant rehabilitation was achieved. Their sociability and ability to adapt themselves to the environment improved to a tolerable level. During treatment, no irreversible side effects were observed. It is recommended that the treatment should be performed either at a child psychiatric unit or by a psychiatrist with adequate experiences in this field and preferably at a hospital.

Drainage of interstitial fluid from different regions of rat brain.

Studies were carried out in anesthetized rats comparing dynamics and pathways of interstitial fluid (ISF) drainage from different regions of brain. Rates of drainage from brain and flow into cerebrospinal fluid (CSF) were estimated from the efflux from brain and influx into CSF of radioiodinated albumin (RISA) following microinjection into caudate nucleus, internal capsule, or midbrain: pathways of flow through the subarachnoid space and into lymph were traced from the distribution of horseradish peroxidase and/or Evans blue-labeled albumin after injection into brain. ISF drainage rates (mul X g brain-1 X min-1) estimated for the three injection sites were 0.18, 0.19, and 0.29, respectively. Flow of ISF into bulk CSF sampled from the cisterna magna accounted for 60-75% of efflux from midbrain but only 10-15% of efflux from caudate nucleus or internal capsule. RISA was concentrated in the subarachnoid space, relative to bulk CSF, in sleeves of adventitial tissue surrounding pericerebral arteries, possibly accounting for the low recovery of isotope from bulk CSF. From the subarachnoid space, some fluid drained via olfactory nerve sheaths to retropharyngeal lymph nodes.

Red blood cell/plasma lithium ratio in manic-depressive, schizoaffective, and schizophrenic patients.

The red blood cell/plasma lithium ratio (LR) has been studied in 14 schizophrenic (paranoid type), 22 schizoaffective, and 86 manic-depressive patients. Mean LR proved to be significantly higher in manic-depressive patients (p less than 0.001) as compared to the other two groups which on the other hand did not differ significantly from each other. There was no significant difference in the LR between female and male patients. Analyzing the LR according to family history and subtype of illness (i.e., bipolar I/bipolar II dichotomization) of 86 manic-depressive patients we found that neither sex nor type of illness had consistent influence on LR, but patients with positive family history of affective illness had a significantly higher LR than patients with negative ones (p less than 0.01).

The red blood cell/plasma lithium ratio: marker of biological heterogeneity within bipolar affective illness?

The red blood cell/plasma concentration ratio (LR) was studied in 45 female patients with bipolar affective illness who responded to prophylactic lithium treatment. Patients were subdivided according to bipolar I vs. bipolar II diagnosis and presence vs. absence of a family history of affective illness. Mean LRs were significantly higher in bipolar II patients and in those with a positive family history of affective illness, but there was no relationship between diagnosis and family history. Results indicate that LR is genetically controlled and may be a biological marker distinguishing bipolar I and bipolar II patients, and also patients with positive or negative family history of affective illness.

Preferential vulnerability of dendrites to lithium ion in rat brain and in nerve cell culture.

Preferential swelling and vacuolation of dendrites were observed electron microscopically in different brain regions of rats treated with LiCl in a dose of 6-18 mmol/kg for 1-6 days. The most severe fine structural changes were revealed in the hippocampus. Low-dose (0.33 mmol/kg) lithium treatment lasting for a year did not cause any morphologically detectable alterations in the rat brain. In vitro studies showed a reduction of dendro-axonal process network of neurons measured by morphometric means after lithium exposure. Using different cultures of neuronal and glial cell populations, higher lithium uptake was observed for neuron-enriched cultures.

Alteration of erythrocyte phosphate transport in primary depressive disorders.

Plasma and erythrocyte phosphate levels, concentrations of red cell organic phosphate ester fractions (acid labile and acid resistant phosphate pools) and intracellular ATP content were determined in 16 patients with bipolar depression, in 14 subjects with unipolar depression as a group of primary affective disorders, in 15 patients suffering from neurotic depression and in 45 healthy controls. Simultaneous in vitro measurements were carried out to detect the exchange rates of inorganic phosphate between the extracellular phosphate pool and the different intracellular phosphate fractions, by use of 32P and applying tracer kinetic analysis. Plasma and red cell inorganic phosphate levels, passive phosphate transport and transfer of inorganic phosphate into the membrane ATP pool were significantly lowered in the primary depressive group as compared to the biochemical values observed in the neurotic group and in the healthy controls. The results suggest an alteration in anion transport across the red cell membrane in primary depressive disorders.

Steady-state distribution of lithium during cultivation of dissociated brain cells.

The formation of a steady-state intracellular lithium level was studied in the course of cultivation of dissociated nerve cell cultures obtained from chick embryonic brains. When lithium was given at a concentration of 2 mM, in the nutrient medium, at day 5, a steady state intracellular lithium content was achieved after about 30 min of incubation and it did not change significantly during the time of cultivation up to the 13th day in vitro.

The influence of external sodium and potassium on lithium uptake by primary brain cell cultures at "therapeutic" lithium concentration.

The ionic regulating of lithium homeostasis and steady-state intra:extracellular lithium distribution in the brain can be approached by experimental methods using intact nerve cells in vitro. Primary cultures prepared from chick embryonic brain were applied to study the effect of extracellular sodium and potassium on the lithium uptake of nerve cells at 'therapeutic' lithium concentration (1.5 mM). Lithium influx and the level of steady-state intracellular lithium were significantly reduced by increasing the external sodium concentration. At physiological extracellular sodium level, the steady-state content of lithium in the brain cells was about half of that observed in the presence of 10 mM sodium in the incubation media and the value of the intra:extracellular lithium distribution ratio was below 1. External potassium (0.5 - 3mM) strongly inhibited lithium uptake of the nerve cells. Ouabain (10(-4)M) had no effect on this potassium-sensitive lithium uptake in Tyrode media. Sodium influx studied by isotope tracer methodology was higher in cultures preloaded with lithium as compared to that of the controls. It can be concluded that sodium and potassium ions, at physiological concentrations, significantly influence lithium uptake as well as the intra:extracellular lithium distribution in brain cell cultures.

Clinical significance of sodium-dependent lithium transport in affective psychoses.

The steady state red blood cell/plasma lithium (Li) ratios were determined simultaneously with the in vitro rates of sodium-dependent Li transport of erythrocytes during prophylactic Li therapy in 30 unipolar, 52 bipolar forms of manic-depressive patients and in 58 nonmanic-depressive psychiatric patients as a control group. A reciprocal correlation was found between the Li ratios and the values of Na-dependent Li transport. These transport rates were in positive correlation with the steady state Li contents of red blood cells and that of the plasma. Significant differences were revealed between the different nosologic subgroups in the respect of in vitro rates of Na-dependent Li countertransport. Results are discussed in the light of clinical and pharmacogenetic aspects.

Calcium-dependent potassium transport in progressive muscular dystrophy.

The rates of calcium-dependent potassium efflux of red blood cells in 9 Duchenne muscular dystrophic patients were measured. A significant decrease was revealed in the Ca-provoked K transport when compared with the rates observed in healthy controls. Results are discussed on the basis of the theory of generalized membrane defect in progressive muscular dystrophies.

Sodium-dependent lithium efflux from red cells in affective disorders.

Steady state red blood cell/plasma lithium concentration ratios were determined simultaneously with the in vitro sodium-dependent downhill lithium efflux from red cells during maintenance lithium treatment in 22 bipolar depressed patients, 17 unipolar depressed patients, and 28 psychiatric control patients. The values of the sodium-dependent lithium efflux were significantly correlated with the steady-state lithium levels in red blood cells and plasma. A profound difference in sodium-dependent lithium efflux from red cells was found between controls and bipolar patients and to a lesser degree between controls and unipolar patients.

Na-dependent Li-transport in primary nerve cell cultures.

Primary cultures from chick embryonic brain were used to study the steady state distribution of lithium. The intra/extracellular Li+ ratio decreased by enhancing the external Na+ concentration. Ouabain did not influence this unequality. A phloretin-sensitive component was revealed in the Li uptake at low Na+ concentration. The findings might suggest the existence of a Na+-dependent Li+ countertransport system in these brain cell cultures.

Cell-to-cell contacts in primary cultures of dissociated chicken embryonic brain.

The fine structure of intercellular contacts was studied in primary cultures prepared from chicken embryonic brain. Desmosomes were frequently seen between the glial cells. Synaptic contacts were observed among neuronal cell bodies and neural processes after 8 days in vitro. Gap junctions were revealed between glial elements suggesting a functional role in direct cell communication and providing a morphological basis for previous observations on potassium transport in cultures of dissociated brain cells.

Effects of lithium on morphological characteristics of dissociated brain cells in culture.

Lithium chloride was added in 5 and 10 mM concentrations for different periods of exposition time to dissociated cultures obtained from chicken embryonic brain. When supplementing lithium at day 1 in vitro for five days, a dose-dependent decrease in total protein was observed in the cultures as compared to the sodium-treated controls. Profound reduction was revealed in the length of neuronal processes and in the number of neuronal cell bodies by phase contrast microscopy and by morphometric means. After exposition of lithium in 10 mM concentration for 48 h, beside a slight decrease in number of perikaryons, a marked reduction in process length of neural elements was observed in the 6-day-old tissue cultures. Ultrastructurally, swollen and degenerating nerve processes have been found after lithium treatment suggesting a particular sensitivity of these structures to lithium ion.