Biomedical subjects
Publications and source records attributed to L Demisch.
Rubidium (Rb+) has an antidepressive effect and shortens the circadian period in animals, whereas Li+, another alcalic metal, lengthens it. When we treated a depressive Li+ nonresponder with Rb+, we found an improvement of depression as well as a phase advance of the temperature rhythm in relation to the rest-activity rhythm.
In a double-blind study, melatonin (50 mg) or placebo was administered daily to 25 subjects at 9 am or 7 pm for 1 week. Self-rated fatigue as evaluated by the Stanford Sleepiness Scale (SSS) was significantly increased during the 3 hours following melatonin intake in the morning, whereas, after administration in the evening, no difference between melatonin and placebo could be distinguished. Sleep onset latency slightly decreased in both melatonin groups without reaching statistical significance. No cumulative effects on sleep or behavior were observed. Twelve pituitary and peripheral hormones measured under baseline and partly (in the evening groups) under stimulated conditions before and after the trial did not change. The two most important conclusions are that: 1) the sedative potency of exogenous melatonin depends on the daily time of administration; and 2) the high pharmacological doses used for acute sedation do not seem to have cumulative effects after prolonged application.
The classification of endogenous psychoses is a controversial sector of psychiatry. Differences with regard to the evaluation of course and outcome contribute to this controversy. The course and outcome of a psychiatric illness are basic to the Frankfurt Classification System (FC) of endogenous psychoses. The main groups are process and phasic psychoses (typical and atypical). A third group, encompassing cases which could not be definitely classified at the time of examination, is entitled 'nonclassified endogenous psychoses'. This system was outlined according to the AMDP system and SANS using the cases of 100 patients admitted to the hospital (aged 18-86 years; 57 men, 43 women) and compared with four classifications (ICD-9, RDC, DSM III and Feighner). The listed definitions do not state whether or not a defective symptomatology is absolutely irreversible. Most of the atypic-phasic psychoses of the FC (50-78%) were schizoaffective psychoses according to the other classifications (Feighner, RDC, ICD-9) and most of the process psychoses (85-97%) were schizophrenias according to Feighner, ICD-9, RDC and DSM III. The major reason for the great correspondence (97%) between process psychoses (FC) and DSM III schizophrenias appears to be that 85% of the sample consisted of chronic and not subchronic schizophrenic disorders according to DSM III. On the other hand, about 45% of the ICD-9 and RDC schizophrenias (principally acute and subacute) were not diagnosed as process psychoses according to the FC. In the case of the typic-phasic psychoses, there was almost complete agreement with the other diagnostic systems. Most of the cases in which classification into the group 'process' or 'phasic psychosis' was unclear were diagnosed as schizophreniform disorders according to DSM III (70%) or into nearly equivalent groups according to RDC or ICD-9. Nonetheless, complete equivalency among these similar groups was not possible. In the context of some research aims (e.g. definitions of phenomenological or biological parameters), a classification system based on clearly-defined inclusion and exclusion criteria of such concepts as phasic and process psychoses (in shifts or insidious) is methodologically useful. The FC is suggested as a step in this direction.
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There is no conclusive evidence supporting an interaction between the pineal gland and the hypothalamic-pituitary-adrenal axis. In this study, 11 healthy adults (six women, five men; aged 18-47 years) received a placebo the first night and 1 mg dexamethasone the next night at either 1800 or 2300 h. Administration of 1 mg of dexamethasone was followed by an attenuation of the nocturnal production of melatonin in 9 of 11 subjects. A significant reduction was found between melatonin plasma levels before and after dexamethasone at 0400 h (P less than 0.01, t test for dependent groups). It is suggested that dexamethasone affects nocturnal production of melatonin by means of mechanisms within the pineal gland.
The influence of various antidepressants on the morning levels of plasma melatonin was studied in human volunteers after acute and subchronic administration in weekly increasing doses over a period of three weeks. Two monoamine oxidase (MAO) inhibitors (tranylcypromine: irreversible type A and B; pirlindole: reversible type A), two reuptake inhibitors (maprotiline: selective for noradrenaline; fluvoxamine: selective for serotonin) and an alpha 1/alpha 2-adrenergic and serotonin S2-receptor antagonist (mianserin) were administered to groups of 4 to 7 healthy volunteers each. Two hours after a single oral dose at 9 a.m., at the end of each week and one week after the last dose, morning levels of melatonin were measured using a radioimmunological method. In addition, platelet MAO activity and the uptake of 14C-5-HT into platelets were determined. Plasma melatonin concentrations at 9 a.m. were significantly increased after the intake of 150 mg fluvoxamine the night before; whereas, administration of the same dose in the morning did not lead to increases in melatonin during the day. Following subchronic administration, plasma melatonin levels were significantly increased after the 1st (50 mg/day), 2nd (100 mg/day) and 3rd (150 mg/day) week of fluvoxamine intake in comparison to pre-drug levels. No changes in early morning levels of plasma melatonin were measured in the subjects receiving the other antidepressants, after acute as well as after subchronic administration. The results seem to indicate that following fluvoxamine intake at night, the early morning decline of melatonin is delayed. It is suggested that the underlying mechanism leading to a rise in morning melatonin levels cannot be explained solely on the basis of an inhibition of 5-HT reuptake and that other pharmacological properties of fluvoxamine may be involved.
The incorporation rate of 14C-labeled arachidonic acid (14C-AA) into membrane phospholipids was measured in a group of untreated (greater than 6 months) psychiatric patients (n = 33) and healthy controls (n = 31). Platelets from controls and from patients with schizophrenia (n = 10), schizophreniform disorder (n = 11), schizoaffective disorder (n = 6), major depression (n = 2), or an atypical psychosis (n = 4), diagnosed according to DSM-III, were incubated with 14C-AA. Platelets from patients with a schizophreniform and a schizoaffective disorder incorporated greater than 50% less 14C-AA than the platelets from controls. The incorporation rates of platelets from schizophrenic patients were slightly (18%), but not significantly, reduced compared to controls. Characterization of variables affecting arachidonic acid and phospholipid metabolism may be helpful in studies focused on the assessment of first-episode psychotic patients and in long-term outcome studies.
Thirty-nine subjects with chronic insomnia were treated with L-tryptophan (L-TRP) in a double-blind, cross-over study. Instead of a placebo, a very low dose of 0.04 g L-TRP was used. The subjects suffered from a sleeping disorder classified as "psychophysiological, persistent". In the subgroup taking the full L-TRP (2 g) dose first, there was a significant difference between the treatment period with the full L-TRP dose and the ineffective dose (placebo). If the placebo was given first, however, there was no significant difference between the two treatment periods. It is suggested that psychological factors are responsible for the diverging results in the two subgroups of patients. On the basis of subjective ratings, it appears that L-TRP is effective in promoting sleep in cases of chronic insomnia.
In an open clinical trial the authors treated 18 hospitalized patients suffering from endogenous depression with brofaromine (CGP 11305A), a competitive, selective, and short-acting inhibitor of type A monoamine oxidase (MAO). Four patients were defined as good responders, as they had a final HAMD score of between 0 and 7 points. Four patients were judged as improved, with final HAMD scores of between 8 and 15 points, while the remaining eight patients failed to respond (final HAMD score greater than or equal to 16 points). The major observations were a beneficial influence on drive in most patients, while paranoid symptoms worsened markedly, rendering the substance contraindicated in psychotic depression. Brofaromine appears to be safe and well tolerated and largely free of side effects. As objectified by the tyramine pressor test, dietary restrictions during brofaromine treatment require less stringency than is the case with conventional MAO inhibitors. The specificity of brofaromine to inhibit deamination is limited to MAO-A, since no reduction in platelet MAO activity was measurable. Sleep EEG recordings in a subset of patients reveals that the amount of rapid eye movement (REM) sleep is significantly reduced during brofaromine treatment.
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Changes in flash but not pattern evoked cortical potentials after subchronic application of the MAO type A inhibitor pirlindole in man are reported. Pirlindole affects the deamination of serotonin and noradrenaline in the central nervous system and has serotonin reuptake inhibiting properties. Flash and pattern evoked cortical potentials were recorded in 6 healthy men before and after a 7 day period of treatment with 3 X 75 mg/day of pirlindole. After drug treatment, an increase in P100 latency to flash stimuli was seen without a change in the latency to pattern stimuli. This indicates that different neuronal systems process flash and pattern stimuli.
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Fourteen depressed patients were given the dexamethasone and ACTH suppression tests. The results of 71% agreed, suggesting that in a subgroup of depressed patients dexamethasone resistance reflects a central rather than peripheral dysfunction of the hypothalamic-pituitary-adrenal axis.
Platelet monoamine oxidase (MAO) activity and personality characteristics were correlated in a sample of 52 men (37 +/- SD 13 years) and 54 women (37 +/- SD 15 years) from a rural community. Personality characteristics were measured by using the Freiburger Persönlichkeitsinventar (FPI-A). In males, weak but significant linear correlations (Pearson product-moment and Spearman rank correlations) were found between platelet MAO activity (p-tyramine and benzylamine as substrates) and the extraversion/introversion dimension. In the females, however, there were no consistent significant correlations between MAO activity and FPI test scores. Comparing the top and bottom 25% of the platelet MAO distribution resulted in a significant difference for the second order factor extraversion in the group of men but not in the group of women. The significant correlation between MAO and introversion could not be attributed to cigarette smoking, food consumption, alcohol, or drugs. In accord with previous biochemical-behavior research, it is suggested that reduced platelet MAO activity may, to some extent, reflect an impulsive personality type.
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