Ole J. Rafaelsen

Cerebrospinal fluid adrenaline and noradrenaline in depressed patients.

Mean adrenaline concentration in cerebrospinal fluid measured by a sensitive and specific isotope‐derivative assay was significantly lower in 15 depressed patients during illness compared with 18 control subjects. At the time of recovery cerebrospinal adrenaline levels had increased markedly to normal levels. Cerebrospinal fluid noradrenaline did not differ in patients compared with controls. The present findings suggest that adrenaline as a neurotransmitter may be involved in affective disorders.

LITHIUM MAINTENANCE TREATMENT OF MANIC-MELANCHOLIC PATIENTS: ITS ROLE IN THE DAILY ROUTINE

The purpose of this study was to evaluate the desired and undesired effects of relapse‐preventive lithium treatment given routinely to manic‐melancholic patients who had accepted the necessity of a strict tablet regime. The evaluation was based upon case record data and various rating scales, and 76 patients took part in the investigation. Our results showed that in 24 % of the patients treatment was discontinued. This was due to side effects in 16 % and to insufficient effect in 8% of the cases. The suicide risk was not eliminated, and 29 % of the patients were receiving additional antidepressive or antimanic treatment at the test day. On the other hand, 78 % of the patients rated the relapse‐preventive lithium effect as moderate to excellent. Indirect evidence was obtained in support o a stabilizing effect of lithium on the emotional control in bipolar patients. The most frquent complaints during lithium treatment were tremor and increased thirst.

LITHIUM TREATMENT AND WEIGHT GAIN

The problem of lithium maintenance treatment and weight gain was examined in 70 manic‐melancholic patients who had been in treatment for 2 to 10 years. Their case records were reviewed and they answered a questionnaire.

Cannabis and Alcohol: Effects on Simulated Car Driving

The effects of cannabis and alcohol on simulated car driving were studied. Cannabis resin containing 4 percent Δ1-tetrahydrocannabinol was administered orally in three doses equivalent to 8, 12, and 16 milligrams of that component. Alcohol was given orally in one standard dose of 70 grams. Both cannabis and alcohol increased the time required to brake and start, whereas alcohol increased while cannabis decreased the number of gear changes. An effect of dosage on response was observed with cannabis.

Lithium treatment: does the kidney prefer one daily dose instead of two?

Renal structure and function were investigated in two groups of long‐term lithium treated patients. Lithium was administered in two different ways either in a one‐dose per day schedule where the whole dose of lithium was given between 8 and 10 p.m. or in a schedule where the lithium dose was given, divided into two or three doses, during the day. Kidney biopsy was performed, and structural changes in the kidney tissue were determined together with 24‐h urine volume in the individual patients. The functional as well as the structural changes were most pronounced in patients given their lithium in divided doses during the day. Lithium may be more harmful to the kidney when the lithium administration gives a relatively constant serum lithium level than when the administration causes greater variations including peak values and low minimum levels in serum lithium. The reason for this might be that a number of regenerative processes only occur in periods with low lithium concentrations.

Lithium treatment regimen and renal water handling: The significance of dosage pattern and tablet type examined through comparison of results from two clinics with different treatment regimens

For many years two Danish psychiatric hospitals have used different lithium treatment regimens. In one, slow-release tablets were given in two daily doses and, in the other, conventional tablets were given in a single daily dose. In both hospitals many patients developed polyuria. Multiple regression analyses with sex, age, treatment duration, serum lithium concentration, and treatment regimen as predictor variables showed that the two treatment regimens did not affect the glomerular filtration rate or the proximal reabsorption differently, but that distal water reabsorption was significantly less affected and polyuria less pronounced in the patients given conventional tablets once daily than in those given slow-release tablets twice daily. The authors are divided among themselves as regards the implications of these findings.

5-HT and 5-HIAA in cerebrospinal fluid in depression

CSF 5-HT and 5-HIAA were measured in endogenously depressed patients (ICD-9) (n = 23) and controls (n = 11). Distribution of sex, age and body height was similar in the two groups. Non-parametric statistics were used. In depressed patients CSF 5-HT concentrations were found to be higher (P less than or equal to 0.01) than in controls. A further classification of the depressed patients by the Newcastle Scale showed that the highest values were found in the endogenous group compared to the non-endogenous group (P less than or equal to 0.02). CSF 5-HIAA was found to be equal in the two groups, even when pairs matched for height were compared. No relation between clinical recovery due to drug treatment and changes in CSF 5-HT was seen. Our data support a possible involvement of 5-HT in the biology of depression, but the anatomical and functional levels of a serotonin derangement are still unknown.

Lithium action on glycogen synthesis in rat brain, liver, and diaphragm

Abstract Intracisternal injection of 9 to 18 μmoles lithium chloride caused an increase in rat brain glycogen. Intraperitoneal injection of 500 to 1200 μmoles lithium chloride increased both brain and diaphragm glycogen, whereas liver glycogen decreased. Blood glucose varied with the time passed after intraperitoneal injection of lithium chloride, initially being 25 per cent higher and thereafter lower than the control rats. Correlation between blood glucose and liver glycogen is discussed.

Cannabis and alcohol: Effects on estimation of time and distance

The effect of cannabis and alcohol on estimation of time and distance during simulated car driving was studied. Cannabis resin containing 4% δ1-tetrahydrocannabinol (THC) was administered orally in 3 doses equivalent to 8, 12, and 16 mg THC. Alcohol was given orally in one dose of 70 g. The subjects were 8 men, 21 to 29 years old. Cannabis showed much stronger effect than alcohol on the estimation of time and distance. The effect of cannabis was more marked on the “subjective” than on the “objective” estimation. A dose-response type of effect was seen on cannabis.

HLA antigens and manic-depressive disorders: further evidence of an association.

One hundred and seven unrelated Danish patients considered to be manic-depressive according to strict diagnostic, symptomatic and course criteria were typed for antigens of the HLA system, the major histocompatibility system in man. Preliminary results from the first 47 patients had previously been reported to suggest a positive association between manic-depressive disorders and HLA-A3, HLA-B7, and HLA-Bw16 and a negative association between such disorders and HLA-B8. Results from the extended series provide confirmatory evidence that there is a positive association between manic-depressive disorders and HLA-Bw16 and also strongly suggest a positive association between HLA-B7 and such disorders. HLA typing may prove to be a useful way of identifying sub-groups of manic-depressive patients for other biological studies. The associations described provide a potential lead for formulating hypotheses about the nature of the biological mechanisms which predispose to manic-depressive disorders.