H.M. van Praag

Neuroendocrine disorders in depressions and their significance for the monoamine hypothesis of depression

This article discusses the results of recent neuroendocrinological research in depressions. The abnormalities found in a given category of vital depressive patients ‐ cortisol hypersecretion, decreased growth hormone response to insulin hypoglycaemia and decreased luteinizing hormone secretion in menopause ‐ are believed to be due to deficient noradrenalin‐(NA)‐ergic activity in the hypothalamus. Thus explained, they support the so‐called MA (monoamine) hypothesis, which postulates that a functional NA deficiency in the brain plays a role in the pathogenesis of certain types of vital depression.

Central monoamine metabolism in depressions. II. Catecholamines and related compounds

CA research in depressions is reviewed. The present situation can be outlined as follows: Vital depressive patients may show central CA disorders that point in the direction of CA deficiency. In principle, this deficiency can be a primary phenomenon or a secondary development: the result of hypersensitivity of postsynaptic CA receptors. The former possibility is considered more plausible than the latter. The DA disorder seems to be related to motor retardation and loss of initiative and probably plays a role in their pathogenesis. There is no reason to assume that this disorder is a predisposing factor. The NA disorder is not related to motor symptoms. Its causative significance is still uncertain. An important byproduct of CA research in depressions is the momentum it gives to attempts to “translate” behavior disorders in terms of disturbed psychological functions. Such a functional psychopathology could be an important supplement to the traditional, more syndromal, and nosological classification of psychiatric conditions.

The scientific foundation of anti-psychiatry

Anti‐psychiatry has exerted a substantial influence on the thoughts of workers in the field of mental hygiene; on those of the psychiatrically trained, but even much more on those without psychiatric training. Consequently it seemed important to me to investigate the strength of the foundation of this school of thought. This has been the objective of this study. The point of crystallization of anti‐psychiatry is the labelling theory on the origin of deviant behaviour. The scientific status of anti‐psychiatry stands or falls with that of the labelling theory. Since this theory has not been formulated in verifiable hypotheses, I ventured to formulate “theses”, and then tested these against empirical obtained data. The results of this study were largely negative. The empirical material does not support the labelling theory, and in many cases even contradicts it. Consequently anti‐psychiatry ‐ as a model to explain the development of psychological disorders ‐ has not a leg to stand on.

Neuropeptides. A New Dimension in Biological Psychiatry

Publisher Summary In the past 20 years, research into biochemical determinants of disturbed behavior has focused mainly on the central monoamines (MA). Other central transmitters either did not fulfill these criteria, or did so only to a partial extent. An example is acetylcholine. The discovery of the neuropeptides was of importance to biological psychiatry for two reasons. The first is a general reason: neuropeptides represent a new principle in neurobiology, that of hormone-like compounds produced in the brain, whose target is the brain. The second is a specific biological psychiatric reason: the neuropeptides have added a new dimension to human brain and behavior research, supplementary to the MA dimension. This chapter discusses the relation between neuropeptide and MA systems.

Tablets and talking—A spurious contrast in psychiatry

Pharmacotherapy and psychotherapy of psychiatric patients are not given equal appreciation. Particularly in syndromes with marked psychogenic or psychosocial overtones, psychotherapy is regarded as the causal therapy par excellence. In these cases (the vast majority), psychotropic drugs are believed to have at best a symptomatic importance and to entail the risk of effacing the true causes. I consider this view to be as unfelicitous as it is wrong, because: (1) Psychosocially determined behavior disorders, too, have a neurochemical substrate; (2) It is by all means sensible to make an attempt to normalize behavior by correction of this substrate; (3) Normalization of the cerebral substrate with the aid of pharmacotherapy is no less a causal type of therapy than is reduction of the pathogenic input with the aid of psychotherapy; (4) This means that pharmacotherapy and psychotherapy are complementary, and that each separately is an incomplete therapy. This argument is valid where psychotropic drugs with a relatively specific effect are available, as they are for the vital depressions and psychoses of the schizophrenic type. In these groups of patients, empirical findings confirm the theoretical expectation formulated (4) above. It is postulated that, for the treatment of neuroses which has so far been based entirely on psychotherapeutic intervention, much is yet to be expected of future developments in psychopharmacology.

Chemoprophylaxis of depressions An attempt to compare lithium with 5‐hydroxytryptophan

There are indications that the group of vital (‘endogenous’) depressions encompasses a subgroup with central 5‐HT deficiency and that this factor contributes to the development of the (or some) depressive symptoms instead of resulting from them. In a majority of patients the suspected S‐HT deficiency persists even when the depressive symptoms have disappeared and the medication has been discontinued. This led us to the hypothesis that the disturbed central 5‐HT metabolism is not a direct causal, but a predisposing factor. If this is true, then abolition of the suspected 5‐HT deficiency, for example with the aid of 5‐HTP, can be expected to have a prophylactic effect. This hypothesis was investigated in this study and confirmed. 5‐HTP reduces the relapse rate in recurrent vital depressions with a unipolar and those with a bipolar course. This effect would seem to be most pronounced in patients whose disorders of central 5‐HT metabolism are persistent. Tentatively it was concluded that 5‐HTP seems to be inferior to lithium in bipolar patients and at least equivalent to lithium in unipolar patients. This problem, however, is still under investigation.

Psychopsychiatry: can psychosocial factors cause psychiatric disorders?

It is a widely accepted view today that psychosocial factors can cause psychiatric disorders. However, this view has, as yet, no firm foundation of verifiable facts. This paper outlines some research strategies that can provide data in favor of or against this theory: (1) systematic analysis of life events preceding psychiatric disorders, covering both stable events and interactional events; (2) vulnerability research on three levels (biologic, psychological, and sociological), aimed at factors that could explain the increased vulnerability of some individuals to the detrimental effects of life events; (3) pathogenesis research, aimed at analyzing how psychosocial stress disrupts cerebral systems, and discovering which of these disruptions is responsible for disturbed behavior, and (4) research into the efficacy of combined biologic (mainly pharmacotherapeutic) and psycho(socio)therapeutic methods. Some results obtained in these areas of research are discussed. The central idea of this study is that psychosocial and biologic factors do not operate independently but in close interaction. This seems a cliche, but is not, as clearly indicated by the scantiness of relevant research so far carried out. This gap is to be filled if psychiatry is to maintain and reinforce its status as a medical discipline.

Effect of des-Tyr1-γ-endorphin on serotonin metabolism in rat brain regions

Intracerebroventicular (i.c.v.) administration of des-Tyr1-γ-endorphin (0.1 and 1.0 μg) caused a decrease of the serotonin (5-HT) concentration of the hippocampus. The concentration of 5-HIAA and the pargyline-induced alterations in 5-HT and 5-HIAA were not affected. No effects were noticed in other brain regions.

Endorphin research in schizophrenic psychoses

Abstract The discovery of the endorphins has opened up a new dimension for research into the biological determinants of schizophrenic behavior. However, it would be premature to advance an endorphin hypothesis on the pathogenesis of schizophrenic psychoses at this time. Technical difficulties have so far been an obstacle in the study of the human central endorphin metabolism. The therapeutic aspect of endorphin research shows some interesting features. Opiate (endorphin) antagonists certainly do not seem to be universal antipsychotics, but undoubtedly it is worthwhile to continue the search for subgroups that are susceptible to these compounds. The reverse of this strategy has also been applied: administration of endorphins to schizophrenic patients. Of the three compounds used in this context, β-endorphin, a synthetic met-enkephalin derivative and DTγE, the latter is the most interesting. It is a naturally occurring fragment of γ-endorphin which lacks morphinomimetic effects and has certain pharmacological as well as clinical properties in common with the traditional neuroleptics. This compound may well open up entirely new perspectives for the treatment of schizophrenic psychoses.