Lothar Adler

Administration of tryptophan-enriched diets to pregnant rats retards the development of the serotonergic system in their offspring

It is well established that an increased availability of tryptophan stimulates serotonin synthesis not only in the adult but also in the developing brain. In order to study the influence of a permanently increased supply of tryptophan on the developing central 5-HT-system, female rats were fed a tryptophan-enriched diet from mating throughout pregnancy and lactation. The effect of this dietary regime was assessed by measurements of neurochemical markers of 5-HT innervation in the developing brain of their offspring. A diminished content of 5-HT, a decreased activity of tryptophan hydroxylase and a reduction of crude synaptosomal high-affinity 5-HT uptake was found in the cortex and in the brain stem of 5 day old rat pups of mothers fed the tryptophan-enriched diet. The postnatal increase of all three markers of serotonergic innervation in the offspring of these mothers was retarded. Both the initial depletion and the delayed maturation of 5-HT content, of tryptophan hydroxylase activity and of synaptosomal serotonin uptake were more pronounced in the cortex than in the brain stem. Apparently, the increased dietary intake of tryptophan throughout pregnancy and lactation caused a delayed outgrowth of 5-HT axons and/or reduced collateral sprouting and synapse formation in the brain of the developing offspring.

Effects of indirectly acting 5-HT receptor agonists on circulating melatonin levels in rats

Because circulating melatonin levels are generally thought to be under the strict control of pineal N-acetyltransferase, little attention has been paid to the impact of an altered availability of serotonin (5-HT) on melatonin formation. In order to see whether melatonin synthesis is stimulated by an increased availability of free, cytosolic 5-HT, we studied the effects of 5-HT precursors, 5-HT releasers and reuptake inhibitors and of monoamine oxidase inhibitors, alone and in combination, on circulating melatonin levels in experimental animals. The administration of tryptophan and 5-HT-releasing drugs (fenfluramine, +/- 3,4-methylenedioxymethamphetamine) to rats caused a dose- and time-dependent elevation of circulating melatonin levels during the day and night. This increase in melatonin was further enhanced by inhibition of monoamine oxidase. The elevation of plasma melatonin caused by 5-HT-releasing drugs was prevented by prior administration of fluoxetine. Monoamine oxidase inhibitors and fluoxetine alone had no effect on circulating melatonin levels. These findings indicate that the administration of indirectly acting 5-HT receptor agonists which increase the free cytoplasmic pool of 5-HT may also elevate circulating melatonin levels. The results of this study suggest that the rate of pineal melatonin synthesis is dependent on the free cytoplasmic pool of 5-HT in pinealocytes and that the drug-induced elevation of this pool stimulates melatonin formation and increases circulating melatonin levels. At least some of the effects of indirectly acting 5-HT receptor agonists, e.g. on sleep, mood, food intake, pain perception, and neuroendocrine secretion, may therefore be mediated by the elevation of circulating melatonin and the subsequent activation of central melatonin receptors.

Endocrine Correlates of Personality Traits: A Comparison between Emotionally Stable and Emotionally Labile Healthy Young Men

An initial sample of 120 healthy young men was screened by a personality questionnaire and 15 subjects each with highest and lowest scores respectively on emotionality (emotionally labile, EL subjects and emotionally stable, ES subjects) were recruited for a study on the relationship between the degree of emotionality and the basal secretion of stress-sensitive hormones during night-time. The nocturnal urinary excretion of cortisol, testosterone, adrenaline, noradrenaline and melatonin was measured over a period of 5 consecutive nights. The average amounts of each hormone excreted per night were not different between the two extreme groups. The variability of the excretion during the 5 nights of cortisol and testosterone, but not of adrenaline, noradrenaline and melatonin, was significantly higher in EL compared to ES subjects. The larger fluctuations in the nocturnal secretion of these two (and no other) hormones in EL subjects indicate that emotional lability is associated with a more labile regulation of cortisol and testosterone secretion. The observed intraindividual variability of basal stress hormone secretion may contribute to the vast interindividual variability noticed in psychoneuroendocrine stress research, especially in emotionally labile subjects.

Relationship between Nocturnal Urinary Cortisol Excretion and Symptom Severity in Subgroups of Patients with Depressive Episodes

Introduction: The aim of this naturalistic study was to gain more information about the elevation of basal hypothalamic-pituitary-adrenal (HPA) activity in relationship to symptom severity in specific subtypes of depressive episodes. Method: Hamilton Depression Rating Scale scores and aggregated nocturnal urinary cortisol excretion were measured in 4 groups of inpatients with depressive episodes (n = 48; monopolar nonpsychotic, monopolar psychotic, bipolar nonpsychotic and bipolar psychotic) at the beginning and at the end of inpatient treatment. Results: The initial elevation of nocturnal urinary cortisol excretion was most pronounced in psychotic patients. At the end of treatment, the Hamilton Depression Rating Scale scores had decreased significantly in all patients to comparable levels, whereas the nocturnal cortisol excretion values were still relatively elevated in mono- and bipolar psychotic patients compared to mono- and bipolar nonpsychotic ones. Conclusion: The observation that the basal HPA activity remains elevated even after remission of symptoms in patients with psychotic depression supports the concept that a dysfunctional regulation of the HPA system is possibly a trait- rather than a state-related feature.

Definition des Kernbereichs ärztlicher Tätigkeit im psychiatrisch-psychotherapeutischen Fachgebiet – Voraussetzung für jede Delegation

Based on legal jurisdiction, knowledge of the psychiatric-psychotherapeutic field and insight into the necessity of a new allocation of responsibilities in the overall therapeutic service of a clinic, the core areas of medical activities are defined for the first time, innovative organisational approaches to the reorganisation of therapeutic service are presented and discussed against the background of qualified staff deficit, introduction of an OPS coding for inpatient psychiatry and economic constraints.

Effects of hypnotics on sleep quality and daytime well-being. Data from a comparative multicentre study in outpatients with insomnia

The effect of treatment (28 days) with zopiclone, triazolam, flunitrazepam and placebo on sleep quality and daytime well-being was proven in a randomised, double-blind, parallel group, multicentre study in private practice. Results of an exploratory statistic of treatment efficacy in a subgroup of 1,291 patients suffering from insomnia are presented. Patients met the following criteria: insomnia lasting at least four weeks and the presence of at least two of the following: 1) sleep latency >/= 45 minutes, 2) total sleep time </= 6 hours, and 3) nocturnal awakening >/=3 times. Treatment efficacy was assessed according to the following factors: either a shortening of sleep latency by at least 15 minutes, or prolongation of total sleep time by at least 20%, or reduction of the number of nocturnal awakenings to three or less and a refreshed feeling in the morning as well as no impairment in daytime well-being due to tiredness or anxiety. The total response rate was markedly higher with zopiclone (42.3%; p = 0.0003) than with placebo (29.0%). Triazolam (36.6%; p = 0.0905) and flunitrazepam (33.1%; p = 0.3401) were also more effective than the placebo, but they both tended to have a lower response rate than with zopiclone (p = 0.1199 and 0.0151, respectively). Total response was found to be essentially a reflection of the response of the socially important parameter of daytime well-being. These results suggest that zopiclone is more effective in the treatment of insomnia than either triazolam or flunitrazepam. Since the response of daytime well-being to therapy was generally poor, this parameter embodies the next main therapeutic challenge in the treatment of patients with insomnia.

Ärztemangel im psychiatrischen Krankenhaus – Zukunftssicherung durch Neuordnung des ärztlichen Dienstes

Increasing psychiatric disorder treatment need, increased work load, changes in the working hour regulations, the nation-wide shortage of physicians, efficiency principle and economisation can necessitate a reorganisation of medical services. The essential steps and instruments of process optimisation in medical services for a psychiatric clinic are elucidated and discussed in the context of demographic changes, generation change, and a new concept of values.

Rechtliche Aspekte von Delegation und Neuorganisation ärztlicher Tätigkeiten im psychiatrischen Fachgebiet

Current psychiatric-psychotherapeutic in-patient care takes place in an area of tension between increasing treatment requirements and the persistent lack of qualified staff. The optimisation of the diagnostic-therapeutic procedures in a clinic helps to reduce existing care deficits or to generate resources for future developments. The subject of delegation and substitution of medical services is considered in this context. Inadequate knowledge of the legal situation on the part of the decision makers impairs the indispensable trustful cooperation among the professions and adds to the uncertainty of all those concerned. The present paper outlines the legal, organisational and health policy aspects of delegation and the reorganisation of medical activities in the field of psychiatry.