The significance of the serum levels of vitamin B-1 and magnesium in delirium tremens and alcoholism.

The relation between serum levels of vitamin B-1 and magnesium at admission, and the clinical state was studied in hospitalized patients with either alcoholism or delirium tremens. Vitamin B-1 was deficient in the delirium group, magnesium in both groups. There was no correlation between vitamin B-1 and magnesium levels. Patients with an unfavorable outcome at discharge had lower vitamine B-1 levels and a higher age than patients with a favorable outcome in either group. The magnesium deficiency is discussed for longstanding malnutrition in both groups, the vitamin B-1 deficiency for an unusual high intake of alcohol before delirium tremens started.

Hyperventilation and panic attacks.

The symptoms of hyperventilation syndrome and panic disorder are very similar. A questionnaire was used to assess the incidence of panic disorder in 274 patients; 35% of the patients with hyperventilation and only 5% of the non-hyperventilating patients showed panic disorder. The authors conclude that hyperventilation plays an important role in panic disorder and in generalized anxiety disorder.

The clinical significance of disordered renal excretion of xanthurenic acid in depressive patients.

Xanthurenic acid is a metabolite of L-tryptophanicotinic acid ribonucleotide biosynthesis. The excretion of xanthurenic acid from urine 24 h after ingestion of 5 g L-tryptophan is increased in depressive patients, and 17-hydroxycorticosteroids are considered of primary importance to this disorder. However, in this study, the excretion of xanthurenic acid and 17-hydroxycorticosteroids did not correlate with the scores of the Raskin depression scale, Hamilton depression scale, Zung depression scale, or the Zung anxiety scale in depressive patients. The patients were treated with either pyridoxine plus L-tryptophan, a presumably serotonin-enhancing treatment (n = 10) or maprotiline, a noradrenaline-enhancing drug (n = 10). Repeated measurements showed no differences between treatments after 2 or 4 weeks of treatment. The improvement in xanthurenic acid excretion precedes clinical improvements in depression. The excretion of xanthurenic acid only at 2 weeks correlated significantly with the anxiety and depression scores at 4 weeks, making prediction of clinical improvement possible. The neurobiological mode of action on noradrenergic or serotonergic neurons of antidepressant medication is of questionable significance to their therapeutic effect.

Kinetics of L-tryptophan in depressive patients: a possible correlation between the plasma concentrations of L-tryptophan and some psychiatric rating scales.

The plasma concentration and flux of L-tryptophan are abnormal in primary depressive patients, according to the literature. The plasma concentrations of L-tryptophan over a 6-h period after ingestion of 5 g L-tryptophan were investigated and did not differ significantly between depressive patients and controls during the absorption, distribution, and elimination phases. There was no correlation between the plasma concentrations with anxiety or depression scores, or with the excretion in urine of 17-hydroxycorticosteroids and xanthurenic acid during the 24 h after L-tryptophan. Treatment with either 125 mg pyridoxine (three times daily with meals) and L-tryptophan (3 g at 10 PM) or with maprotiline (100 mg at 10 PM) had no influence on the plasma concentrations of L-tryptophan after 2 or 4 weeks of treatment. This excludes L-tryptophan deficiency as a pathogenic factor of depression in the patients studied. No kinetic differences could be demonstrated in the depressive patients, making differences in body compartments or flux of L-tryptophan unlikely to be of pathogenic importance to depression.

First report of mirtazapine overdose.

This report describes what is thought to be the first case of mirtazapine overdose occurring since the introduction of the antidepressant drug (Remeron) in the Netherlands in 1994. It is suggested that mirtazapine has a benign side effect profile when taken in overdose.

Treatment of the hyperventilation syndrome with bisoprolol: a placebo-controlled clinical trial.

The hyperventilation syndrome (HVS) can be regarded as a form of panic disorder associated with a relative increase in sympathomimetic tone, the effects of which can be counterbalanced by beta-adrenoceptor blockade. The efficacy of the beta-blocker bisoprolol was investigated in a double-blind placebo-controlled randomised crossover trial involving 60 patients from 17 general practices. Following a single-blind placebo prephase, patients who met the inclusion criteria were randomised to treatment with either 5 mg bisoprolol or an identical-looking placebo tablet once daily for three weeks. They were then crossed over to the other treatment arm. At the end of each treatment phase the number of hyperventilation attacks and the severity of symptoms were assessed and side effects recorded. The number of attacks decreased from 4.04 per week at baseline to 3.52 with placebo and to 1.26 with bisoprolol. The decrease of attacks with bisoprolol was significant (p < 0.05) compared to baseline and placebo. The severity of the complaints improved from 29 (scale 0 to 64) at baseline not significantly to 26 with placebo and significantly (p < 0.05) to 15 with bisoprolol. No serious side effects were reported. Five milligrams of bisoprolol once daily is effective and safe in the maintenance of symptom reduction in patients with the hyperventilation syndrome.

Adult metachromatic leukodystrophy. Arylsulphatase-A values in four generations of one family and some reflections about the genetics.

The authors describe an investigation of Adult Metachromatic Leukodystrophy in a Dutch family, of which two persons were affected. The studies of leukocyte arylsulphatase-A activity were made in 47 members of 4 generations of the same family. The propositus, a 30-year old man, showed a conspicious organic brain syndrome, that progressed in two years to a complete dementia. His leukocyte, liver and kidney arylsulphatase-A activities (ASA) were very low; leukocyte-ASA activity increased after aceto-salicylate. His brother had died at 34 years, after a progressive debelitating neuropsychiatric illness of eight years; postmortem metachromatic leukodystrophy was diagnosed. In all living family members, urine and leukocyte arylsulphatase-A activities were determined. The findings are discussed in relation to the genetics and pathogenesis of this adult form of metachromatic leukodystrophy. Allelic heterozygoty is proposed as inheritance model in this family. Suggestions for further research are made.

The chronopathology of premenstrual psychopathology.

Psychopathology may occur with the following premenstrual chronopathologic characteristic : the symptoms begin about four days before menstruation and end within the first four days of menstrual flow. For the diagnosis of "premenstrual tension syndrome" (PMTS) the complaints must be present for four consecutive menstrual cycles. According to DSM-III criteria PMTS is a mental disorder of shared phenomenology. The major etiologic factor is hyperprolactinaemia alone or in combination with reduced plasma levels of oestrogen or progesteron during the final luteal phase. The premenstrual chronopathology of these three forms of hyperprolactinaemia may explain the pathogenesis of PMTS. Lithium appears to have a favourable effect on the chronopathologic disorder. As to the molecular mechanisms of the pathogenesis, the intracellular affects of prolactin or prostaglandin PGE1 are important. From a pathophysiologic point of view PMTS may be considered a deficiency of PGE1 activity in the hypothalamus and the temporal cortical areas. This is antagonized by lithium. Premenstrual exacerbations of depression or psychosis differ from PMTS as to their clinical symptoms, location, pathogenesis, pathophysiology and treatment. From a pathophysiologic point of view PGE1 may be involved here, too. Implications for further investigation are discussed.

Gamma-hydroxybutyric acid as hypnotic. Clinical and pharmacokinetic evaluation of gamma-hydroxybutyric acid as hypnotic in man.

Gamma-Hydroxybutyric acid (GOH) was administered to three groups of four patients in 50, 75 or 100 mg/kg dose respectively, and sleep effects were scored, by sleep observation and questionnaire; GOH plasma levels were determined at 75-100 mg/kg, saliva and urine excretion at 100 mg/kg. Sleep induction was rapid and irresistible, subjects awoke at plasma levels of 90 micrograms/ml; sleep scores were good for 75 mg/kg, excellent for 100 mg/kg, notably on mood. For 75 or 100 mg/kg GOH had virtually disappeared from the blood eight hours after intake; twelve hours after intake no more GOH was detectable in urine; no correlation between plasma- and saliva levels was found. Plasma levels for 100 mg/kg dose were not at an anaesthetic level. So, GOH is a safe and good hypnotic at 75 or 100 mg/kg in clinical use.

[Pharmacotherapy of the hyperventilation syndrome]. / Pharmacothérapie du syndrome d'hyperventilation.

Hyperventilation may be induced by several organic factors. The HVS-hyperventilation and symptoms such as hypertonia and pain-hypocapnia and disturbance of the acid-base balance--other symptoms--anxiousness--hyperventilation--etc. In the adaptation-hyperventilation and symptoms such as hypertonia and pain,-hupocapnia and disturbance of the acid-base balance-other symptoms--anxiousness--hyperventilation--etc. In the adaptation process one distinguishes the load, the strain and a tension or counterforce (stress). In the cause and effect relationship between the adaptation process and a specific pathology, it is obvious that the strain is the only element capable of eliciting the specific pathology or syndrome. Stress is a compensation for the strain and is therefore beneficial to the organism. The strain is associated with, amongst other things, anxiety and changes in the pyridoxine-L-tryptophan metabolism (nicotinic acid-ribonucleotide synthesis). Stress depends to a large extent on the intact serotonergic transmission in the cerebrum. But serotonin synthesis is critically dependent on the pyridoxine-L-tryptophan metabolism. Benzodiazepines improve the hyperventilation, anxiousness and strain, if these are of the free-floating anxiety type. Tricyclic preparations improve anxiousness in as much as it assumes the character of fear, phobia or an anxiety attack. They are active against strain when that reveals itself as an anxiety attack. Pyridoxine and L-tryptophan as serotonergic agonists, improve the hyperventilation, have a beneficial effect on symptoms such as hypertonia and pain, are effective against anxiousness and anxiety and potentiate the stress. In addition they directly correct the property of strain, i.e. the disturbance of the nicotinicacid-ribonucleotide synthesis. Clomipramine is the most potent serotonergic agonist available. That substance has a favourable effect on hyperventilation, hypertonia and pain, on anxiousness that expresses itself as fear, phobia or an anxiety attack. It favours stress. Further investigation is desirable, in particular of the new serotonergic agonists that have recently been made available or are still to come.

Plasma concentrations of magnesium and vitamin B-1 in alcoholism and delirium tremens. Pathogenic and prognostic implications.

Plasma concentrations of magnesium were low in 32 alcoholics and 19 patients with delirium tremens. Vitamin B 1 was lowered only in delirium tremens. After discharge, 39 patients were in remission and 12 present signs of alcoholic encephalopathy. The development of encephalopathy can be predicted when delirium tremens is associated with a low plasma concentration of magnesium and vitamin B 1 and admission. One can thus conclude that encephalopathy after discharge is not caused in alcoholics by deficiencies in magnesium or vitamine B 1 or both together.

Recent antipsychotics in the treatment of psychoses.

Antipsychotic drugs are effective in psychoses, whatever the etiology of the disorder. The positive symptoms tend to respond more readily. The need for developing new drugs arises from the refractoriness of the negative symptoms, the 10-25% of the patients that are treatment-resistant and the problems of short-, and long-term extrapyramidal side-effects. Thus far, six drugs, differing from the classical antipsychotics, have been licensedfor use: olanzepine, risperidone and quetiapine; the longest registration exists for sulpiride and clozapine while the most recent one is for amisulpride. This review starts with a brief introduction to symptomatology, and takes differences with the classical drugs in pharmacology, pharmacokinetics, clinical aspects and side-effects into consideration. Clozapine, risperidone and sulpiride may be considered for clinical use in refractory patients; these three, olanzapine and amisulpride when extrapyramidal side-effects cause a clinical problem. Amisulpride and sulpiride have a dual therapeutic acion: On negative symptoms at low dose, on positive symptomen at high doses.

Biological markers in psychiatry.

Biological markers in psychiatry are defined as measurable and quantifiable indices of psychiatric disorders. Criteria for biological markers are discussed. The criteria for the assignment of a biological marker to the pathophysiology, pathogenesis, or etiology of a disorder are proposed. None of the biological markers described in the literature for depression, schizophrenia, alcoholism or anxiety as separate disorder fulfills the specified criteria. Most of them can at best be considered as biological markers of the aspecific processes of strain and stress. Free-floating anxiety is the clinical hallmark of strain.

Recent developments in the management of psychosis.

Antipsychotic drugs are effective in psychoses, whatever the aetiology of the disorder. The positive symptoms tend to respond more readily. The need for developing new drugs arises from the refractoriness of the negative symptoms, the 10-25% of the patients that are treatment-resistant and the problems of short-, and long-term extrapyramidal side-effects. Thus far, five drugs differing from the classical antipsychotics have been licensed for use: clozapine, olanzepine, risperidone, sertindole and sulpiride, and in at least some European countries quetiapine is now in the final phase of clinical research. This review starts with a brief introduction to symptomatology, is limited to the registered drugs and addresses differences with the classical drugs in pharmacology, pharmacokinetics, clinical aspects and side-effects. Clozapine, risperidone and sulpiride can be considered for clinical use in refractory patients, and these three together with olanzapine and sertindole are candidates when extrapyramidal side-effects cause a clinical problem.

The clinical significance of an elevated excretion of xanthurenic acid in psychiatric patients.

This study investigations whether the synthesis of nicotinamide out of L-tryptophan is disordered in depression or in anxiety. To this end the excretion of xanthurenic acid (XA) in 24 hours urine was measured after administration of an oral loading dose of 5 grams L-tryptophan. The subjects were depressive, anxious, and alcoholic patients, while other psychiatric patients, served as control group. Anxiety and not depression is the clinical correlate of an elevated excretion of XA. Liver disorder and vitamin B-6 deficiency have to be excluded. A psychiatric control group is necessary.

A literary dessert.

This paper contains an expression of gratitude towards the organizers of the congress 'Psychiatry, Food and Addiction', and the Board members of the Interdisciplinary Society for Biological Psychiatry, of the Sections 'Biological Psychiatry' and 'Psychiatry and Addiction' of the Dutch Society of Psychiatry and the former Editorial Board of Acta Neuropsychiatry. The author has been a long-term board member of the society and cofounder of both sections and cofounder and editor-in-chief of this Journal from 1989 to 1999.