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Biomedical subjects

H M Van Praag

Publications and source records attributed to H M Van Praag.

At least 19 recordsLinked to original sources
PubMed1994

5-HT-related, anxiety- and/or aggression-driven depression.

Mood lowering is considered to be the prime factor in the diagnosis of depression. However, it has been proposed that in a subset of cases of depression, the primary symptoms are anxiety and/or aggression. It has also been shown that these symptoms coincide with disturbance of 5-hydroxytryptamine (5-HT), which is frequently seen in depressed patients and has been suggested to be a vulnerability factor in the onset of depressive phases. If the concept of this proposed subset of depression--termed "5-HT-related, anxiety-and/or aggression-driven depression"--is accepted, this will lead to a review of the mode of diagnosis of depression and a reorientation of research into antidepressant drugs.

Aggression↗
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↗
PubMed1984

Human platelets possess multiple [3H]imipramine binding sites.

Scatchard analysis of [3H]imipramine binding to human platelets over the concentration range of 0.1-250 nM revealed a biphasic concave upward curve. Computer-assisted analysis indicated the best fit of the data by a two-site model with apparent Kd values of 0.68 and 293 nM and apparent Bmax values of 802 fmol/mg protein and 12.72 pmol/mg protein for the high- and low-affinity components, respectively. These results demonstrate the complex manner in which [3H]imipramine binding to human platelets, suggesting a reason for inconsistencies in Bmax values reported in the literature. Further studies of these low- as well as high-affinity sites may help elucidate the functional role of [3H]imipramine binding sites in affective disorders.

Blood Platelets↗
PubMed1982

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

Intracerebroventricular (i.c.v.) administration of des-Tyr1-gamma-endorphin (0.1 and 1.0 microgram) 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.

Animals↗
PubMed1980

Unusual plasma level oscillations of clomipramine in man: a pharmacokinetic and pharmacodynamic dilemma.

Modern bioanalytic methodology has opened up new opportunities to study drug concentrations in the body and thereby gain an understanding of the pharmacokinetics, pharmacodynamics and hence pathways for the clinical efficacy of various drugs. Plasma clomipramine levels have therefore been studied in normal and depressed subjects after oral and intravenous administration. For eight hours after a single dose plasma clomipramine levels behaved in accordance with known pharmacokinetic principles but thereafter, whichever the route used, there were substantial oscillations, minimal in the morning, maximal early in the afternoon and falling in the late afternoon, peak levels being reached on the second or third day. One possible explanation for these oscillations is that at first much of the drug is stored at binding sites from which it is displaced from time by endogenous substances, competing with the parent drug and causing its release back into the circulation. Future studies should include the behaviour of the metabolite desmethylclomipramine, and the effect of repeated doses of clomipramine.

Administration, Oral↗
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↗