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H M Van Praag

Publications and source records attributed to H M Van Praag.

At least 19 recordsLinked to original sources
PubMed1990

Nosological tunnel vision in biological psychiatry. A plea for a functional psychopathology.

Classical nosology has been the major cornerstone of biological psychiatric research; finding biological markers and eventually causes of disease entities has been the major goal. Another approach, one we have designated as "functional," seems possible, attempting to correlate biological variables with psychological dysfunctions, the latter being considered to be the basic units of classification in psychopathology. We have pursued this route for many years, and based on the resulting findings we formulated the following hypothesis. Signs of diminished dopamine, serotonine, and noradrenaline metabolism, as have been found in psychiatric disorders, are not disorder-specific, but rather are related to psychopathological dimensions; i.e., hypoactivity/inertia; increased aggression/anxiety and anhedonia, independent of the nosological framework in which these dysfunctions occur (van Praag et al. 1990). In this paper only the 5-HT data have been discussed. Implications of the functional approach for psychiatry are discussed, including a shift from nosological to functional application of psychotropic drugs. Functional psychopharmacology will be dysfunction-oriented and therefore inevitably geared towards utilizing drug combinations. This prospect is hailed as progress, both practically and scientifically.

5-Hydroxytryptophan↗
PubMed1986

The serotonin hypothesis of (auto)aggression. Critical appraisal of the evidence.

Based on the relation found to exist between low CSF 5-HIAA and suicide attempt, in particular violent suicide attempt, both in depressed and in so-called nondepressed suicide attempters, the conclusion was drawn that decreased central 5-HT metabolism is related to (auto)aggression, rather than to depression. We challenged this conclusion and that for three reasons: Violent suicide attempt accumulates in certain types of depression making it impossible to conclude whether the biological variable relates to (auto)aggression or to that type of depression as such. Nondepressed suicide attempter is a diagnosis that should be based on presuicidal not on postsuicidal data, in order to avoid false-positive diagnoses. Suicide method is not a reliable index of seriousness of the attempt. Risk/rescue ratio should be used instead. Next the data are discussed that do support the hypothesis that diminished 5-HT metabolism in the brain is related to disregulation of aggression. Finally, the hypothesis is launched that both mood and aggression disorders are related to decreased 5-HT metabolism in the CNS. This would provide a biological explanation for the clinical observation that disorders in mood and in aggression often go hand in hand. Biological research of psychiatric disorders gains in informative value as the psychopathological analysis of the phenomena one studies is more comprehensive. Biological suicide research is no exception to this rule.

Aggression↗
PubMed1985

Multiple [3H]imipramine binding sites in brains of male and female Fawn-Hooded and Long-Evans rats.

Comparisons of high- and low-affinity [3H]imipramine binding to whole brain homogenates from adult male and female rats of the Fawn-Hooded and Long-Evans strains were performed. Most strikingly, no significant differences were observed between the two strains in any of the binding parameters, indicating that brain [3H]imipramine binding sites, which may be related to the serotonergic uptake process, appear normal in a strain of rats with serotonin platelet storage pool disease. However, a significant sex difference in high- but not low-affinity whole brain [3H]imipramine Bmax values was observed, with females of both strains having higher densities than males. The observed sex difference in densities of high-affinity [3H]imipramine binding sites necessitates further research into possible sex hormone interactions with this binding site and serotonergic transmitter systems.

Animals↗
PubMed1979

The effect of propranolol treatment in shizophrenia on CSF amine metabolites and prolactin.

Recent reports have suggested that high doses of propranolol may be an effective treatment in schizophrenia. To determine whether such treatment has effects on cerebrospinal fluid (CSF) amine metabolites and prolactin similar to the effects of the neuroleptic drugs, we studied CSF from ten patients before and after propanolol therapy. The initial CSF sample was removed after a drug-free period and propranolol dosage was then increased over 1 week to 1000 mg daily in all ten patients. A second CSF sample was removed after 3 weeks of propranolol therapy. Propranolol levels and prolactin in CSF were measured by radioimmunoassay. Homovanillic acid, 5-hydroxyindoleacetic acid, and 3-methoxy-4-hydroxyphenylethylene glycol were measured by gas chromatography-mass spectrometry. Propranolol had no effect on the prolactin or amine metabolite concentrations. CSF propranolol levels averaged 40 ng/ml (range less than 1--78).

Adult↗
PubMed1979

Color blindness linkage to bipolar manic-depressive illness. New evidence.

Linkage between protanopia and deuteranopia and bipolar manic-depressive illness is demonstrated in a sample of eight informative families ascertained in Brussels. Genetic heterogeneity of bipolar affective disorders is also shown in the present study. These results add new evidence to the hypothesis of X-linked dominant genetic transmission of affective liability in a subgroup of patients with bipolar affective disorders.

Adult↗
PubMed1979

Therapeutical significance of clopimozide in the treatment of chronic psychotic patients.

This report, which concerns both an open and a double-blind study, describes the activity profile and optimum daily dose of clopimozide (R 29 764) investigated in 40 chronic psychotic patients. The results of the open study indicated that clopimozide represents an equal, if not superior, choice versus the other neuroleptics which the patients had been receiving before the open study. Patients sought more contact with those surrounding them, were less preoccupied with their delusions and hallucinations, and showed a better adapted social behaviour. However, these results were not confirmed by the data from the double-blind study-showing that clopimozide was less superior to the placebo than expected on the basis of the open trial. Two hypotheses are advanced to explain this discrepancy: first, the difference in investigational method and second, possible over-dosage of the drug at an average optimum daily dose of 13.95 mg.

Adult↗
PubMed1977

Evidence for a probenecid-sensitive transport system of acid monoamine metabolites from the spinal subarachnoid space.

The location of probenecid-sensitive elimination mechanisms of monoamine metabolites from the cerebrospinal fluid of the cat was determined with ventriculo-cisternal or ventriculo-lumbar perfusion techniques. These techniques were described in detail. Levels of endogenous homovanillic acid and 5-hydroxyindoleacetic acid were assayed in the perfusate. Probenecid administration induced the most marked increase of the levels of the monoamine metabolites in the ventriculo-lumbar perfusates. It was concluded that probenecid blocked the transport of both metabolites from the spinal subarachnoid space.

Animals↗
PubMed1977

On the significance of regional dopamine metabolism in the rat brain for the classification of centrally acting drugs.

3,4-Dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured in the corpus striatum, nucleus accumbens and tuberculum olfactorium of the rat brain, 4 antidepressants, 4 anesthetics, dipropylacetate, ethosuximide and metoclopramide induced a rise of DOPAC and HVA levels in the 3 brain regions. No change was observed after carbamazepine, diazepam or propranolol treatment. Combined treatment with a maximally effective dose of haloperidol and morphine, oxotremorine or probenecid produced an additional rise of DOPAC and HVA levels, while no additional rise was seen with chloral hydrate, chlorimipramine, ether, halothane, metoclopramide or sulpiride. The potency of drugs to increase DA metabolism in corpus striatum relative to mesolimbic structures was estimated. Atypical neuroleptics such as sulpiride could be differentiated in this respect from classical neuroleptics such as chlorpromazine, fluphenazine and thioridazine, by their ability to produce a relatively large increase of metabolite levels in the mesolimbic regions. The heterogeneous group of 14 non-neuroleptics however produced regional changes which were very similar to those of the atypical neuroleptics. DA metabolism in mesolimbic regions, in contrast to striatal tissue, seems to respond more to atypical neuroleptics and non-neuroleptics than to typical neuroleptics.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1977

Controlled study comparing nomifensine and clomipramine in unipolar depression, using the probenecid technique.

1. Central dopamine turnover may be lowered in patients with unipolar endogenous depression particularly when associated with retardation. 2. Nomifensine selectively activates the central dopaminergic system and may be of special therapeutic value in patients with motor inhibition. 3. A double-blind comparison of clomipramine and nomifensine was carried out in patients with recurrent unipolar depression. Biochemical and clinical assessments were carried out weekly for 4 weeks. 4. The mean homovanillic acid level in cisternal liquor of those patients who responded to nomifensine, was significantly lower than the mean level of the total group. 5. The factor "retardation" on the Hamilton Depression Scale was improved more with nomifensine than with clomipramine.

Adult↗
PubMed1977

New evidence of serotonin-deficient depressions.

In 30 patients suffering from vital depression (the syndrome of endogenous depression) a negative correlation was found between the pre-therapeutic post-probenecid CSF 5-HIAA response and the therapeutic response to clomipramine (Anafranil). Clomipramine is a tricyclic antidepressant with a strong potentiating effect on central 5-HT. The following conclusion was drawn: if the cenral 5-HT turnover is diminished in depressions, then correction of this biochemical disturbance leads to alleviation of depressive symptoms. This finding is considered to support the concept of '5-HT-deficient depression'. Five of the 8 clomipramine-resistant patients showed a favourable response to nortriptyline, a NA-potentiating anti-depressant. The pre-therapeutic CSF MHPG concentration in these patients was not related to the therapeutic efficacy of nortriptyline. So, the assumption that these patients have been NA-deficient was not confirmed. However, renal MHPG excretion was not measured and possibly this variable correlates better with cerebral NA metabilism than MHPG in lumbar CSF which is of mainly spinal origin.

Adult↗
PubMed1976

Importance of dopamine metabolism for clinical effects and side effects of neuroleptics.

The authors studied the relation between human central dopamine (DA) metabolism and the clinical effects of neuroleptics. The neuroleptic-induced increase in central DA turnover (an indicator for the degree of DA receptor blocking) was found to be positively correlated with the therapeutic effect of neuroleptics and the development of hypokinetic-rigid symptoms. This supplies a direct argument in support of the contention that DA antagonism is related to the occurrence of clinical effects. The authors also found indications that neuroleptics of different chemical types do not significantly differ in their intrinsic ability to provoke hypokinetic-rigid symptoms, that development of these symptoms depends on the patient's individual susceptibility, and that individual susceptibility is based on relatively low DA turnover.

Adult↗
PubMed1976

Clozapine versus perphenazine: the value of the biochemical mode of action of neuroleptics in predicting their therapeutic activity.

The chemical structure of a neuroleptic does not relaibly predict the exact profile of its therapeutic action. We considered the question whether the biochemical action of a neuroleptic, and specifically the ratio between DA-receptor block and NA-receptor block, might have a higher predictive value in this respect. In this context we carried out a double-blind study of the therapeutic value of clozapine and perphenazine in acute psychoses of varying symptomatology anc aetiology. There are strong indications that clozapine has only a slight inhibitory effect on transmission in central DA-ergic neurons, but markedly inhibits transmission in central NA-ergic neurons, and that the reverse applies to perphenazine. In view of these data we expected perphenazine to be a stronger antipsychotic and a weaker sedative than clozapine, and vice versa. The plausibility of this hypothesis was demonstrated. Partly also on the basis of earlier research, we concluded that the biochemical action of a neuroleptic is a more faithful predictor of its therapeutic action profile than the chemical structure.

Adult↗