Central monoamine metabolism in depressions. I. Serotonin and related compounds
Comprehensive PsychiatryPublished 1 January 1980
H. M. van Praag
Citations98
SJR quartileQ1
SJR score1.72
SNIP1.60
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TL;DR
Research into the possible significance of disorders of the central 5-HT metabolism in the pathogenesis of recurrent depressions is reviewed, with the tentative conclusion that such metabolic disorders are indeed involved in a certain subcategory of vital depressions and play a (possible predisposing) role in the Pathogenesis of these depressions.
Abstract
This article reviews research into the possible significance of disorders of the central 5-HT metabolism in the pathogenesis of recurrent depressions. The available data would seem to warrant the tentative conclusion that such metabolic disorders are indeed involved in a certain subcategory of vital depressions and play a (possible predisposing) role in the pathogenesis of these depressions.The use of 5-HT precursors in depressions is regarded as a potential asset, although the conclusion that real substitution therapy can thus be given would be premature.
Keywords
MedicineNeuroscience
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1,022 Citations1971John D. Fernstrom, R. J. Wurtman
Brain serotonin cocentrations at 1 p.m. were significantly elevated 1 hour after rats received a dose of L-tryptophan and plasma and brain tryptophan levels were elevated 10 to 60 minutes after the injection, but they never exceeded the concentrationis that occur nocturnally in untreated aninmals as result of their normal 24-hour rhythms.
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The data suggest that endogenous depression is a hiochemically heterogenous disease and there may be a subgroup of patients within the endogenous syndrome where indoleamine metabolism is disturbed, and treatment with drugs that influence indoleamines more directly than a typical noradrenaline uptake inhibitor like nortriptyline, may lead to better therapeutic results.
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225 Citations1971H. M. van Praag, Jakob Korf
The influence of i.v. administered probenecid on the 5-HIAA concentration in the CSF was studied in a group of patients with vital (“endogenous”) depression and a non-depressive control group, suggesting that the group of v tal depressions encompasses two biochemically different categories: patients with and patients without demonstrable disturbances in the metabolism of 5-HT in the brain.
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180 Citations1979W.M.A. Verhoeven
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Archives of General PsychiatryCerebral Monoamines and Depression
175 Citations1973H. M. van Praag
Findings lend support to the hypotheses which postulate a correlation between deficient central monoamine metabolism and the occurrence of depressive symptoms and justify the hypothesis that depressive syndromes similar in terms of psychopathological symptoms may nevertheless be based on disparate metabolic substrates.
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Urinary excretion levels of MHPG in one of the patients studied longitudinally did not correspond to the direction of clinical affective state but did reflect anticipated changes during alpha-MPT treatment, suggesting that serotonergic mechanisms are likely involved in the anti-depressant effects of imipramine in man.
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It is interesting that some recent work with animal models of depression has again provided the research clinician with new insights for further experimentation.
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The sum of the ratings for depressed mood, suicidal intent, depressive thought content, and anxiety showed a more rapid improvement in the former group, the difference being already significant after 12 days of treatment, and in the tryptophan group the degree of improvement seemed to be positively correlated to these levels, suggesting that further improvement might have been reached in some patients by increasing the dose of clomipramine.
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It is plausible that disorders of the 5-HT metabolism play a role in the pathogenesis of depression, instead of resulting from them, and suggests that the group of vital depression is heterogenous in biochemical terms.
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In depressions, varying therapeutic effects have been obtained with 5-HT precursors, possibly due to the fact that the group of the depressions is pathogenetically heterogeneous; that, specifically, some types do and other types do not entail disturbances in the central 5- HT metabolism; and that only the former types are “precursor-sensitive”.
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Journal of Neural TransmissionBiochemical post-mortem findings in depressed patients
115 Citations1975W Birkmayer, Peter Riederer
Biochemical human post-mortem studies on depressed patients indicate an unspecific deficiency of neurotransmitters in several brain areas and a circadian disrhythm in depressed patients resulting in lowered VMA- and HVA-levels in urines during the morning and a remission to normal values in the evening.
Archiv für Psychiatrie und NervenkrankheitenThe treatment of depression with L-5-Hydroxytryptophan versus imipramine
94 Citations1977Jules Angst, B. Woggon +1 more
The L-5-HTP results showed no difference compared with the results of an Imipramine treatment in 40 patients in earlier double-blind studies, and the gastrointestinal side effects seemed to be dose dependent.
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87 Citations1977Sheila L. Handley, Todd Dunn +3 more
There was a positive correlation between plasma free tryptophan concentrations and mood state and over the period plasma freetryptophAn concentrations tended to rise and plasma cortisol concentrations to decline.
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81 Citations1979Anna Cristina Åberg, Gunnar Holmberg
Zimelidine, a bicyclic compound, which in animal experiments causes specific inhibition of the uptake of 5‐HT, was tried on 15 patients with depression of endogenous type and produced considerable and highly significant5‐HT uptake inhibition in rat brain slices incubated in blood plasma from the patient under treatment, but no inhibition of NA uptake.
PsychopharmacologyPlasma amino acids as an index for subgroups in manic depressive psychosis: Correlation to effect of tryptophan
66 Citations1976S. E. M�ller, Laura Kirk +1 more
Two biochemical distinct groups of manic depressive patients seem to be present, one group showed a normal pattern of plasma amino acids and was resistant to oral tryptophan medication, and another group, characterized by a relative deficiency of tryPTophan in plasma as measured by the ratio of total plasma tryptopophan to competing amino acids, responded readily to tryaptophan treatment.
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64 Citations1979David Costain, A. R. Green +1 more
When ECS are given to rats in ways similar to those in which electroconvulsive therapy is given to patients with depression, enhancement of behavioural responses to increased 5-HT function is produced.
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61 Citations1973H. Keith H. Brodie, Robert L. Sack +1 more
This chapter presents evidence for a specific indoleamine abnormality in depression and the attempts to correct a suspected deficiency with the serotonin precursor, L-5-hydroxytryptophan (L- 5-HTP), and theoretical advantages compared to L- tryptophan as an agent that could have pharmacological effects.
Approaches to Brain Amines in Psychiatric Patients: A Reevaluation of Cerebrospinal Fluid Studies
54 Citations1978Robert M. Post, Frederick K. Goodwin
Special focus will be given to the time course of biological changes at the synapse, especially more chronic, long-term compensatory and adaptive mechanisms which may be critical to an understanding of the nature of biochemical-behavioral linkage.
Acta Psychiatrica ScandinavicaNeuroendocrine disorders in depressions and their significance for the monoamine hypothesis of depression
53 Citations1978H. M. van Praag
The results of recent neuroendocrinological research in depressions 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.
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50 Citations1978Alec Coppen, Keith Wood
Although exogenously administered oestrogens do not have any therapeutic efficacy in relieving mild residual depressive symptoms of lithium treated patients, they increased the levels of plasma free tryptophan, which reduced the levels in depressed patients.
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Results suggest an association between affective state and the above precursor amino acids with lower concentrations in primary depression and higher ones when anxiety or agitation predominate.
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It is concluded that L-tryptophan probably has some antidepressive action in patients with depressive illness of moderate severity, and both groups of patients improved steadily over the course of four weeks and there were no marked differences between the treatment groups.
Journal of Neurology Neurosurgery & PsychiatryDepression and Schizophrenia. A Contribution on their Chemical Pathologies
36 Citations1978L L Iversen
This is a good book and highly recom that they have identified and rectified a mended and it is in rapidly developing section includes thoughtful and interyoung subspecialities, such as neuroesting comments and discussion.
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30 Citations2017Juan José López-Ibor Aliño, J L Ayuso Gutiérrez +1 more
The treatment with nialamide + l-5-HTP proved to have a shorter delay of onset and patients treated with this combination achieved a fuller recovery than those who were treated with nIALamide alone.
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29 Citations1976W. Pühringer, Anna Wirz‐Justice +3 more
Arguments are presented supporting the assumption that primarily serotoninergic changes underlie these mood effects, and this mode of i.v. application of 1-5HTP represents a practicable strategy for investigating biochemical hypotheses as to serotonin mediated normal and deviant human behaviour, especially in affective disorders.
PsychopharmacologyEnhancement of central norepinephrine and 5-hydroxytryptamine transmission by tricyclic antidepressants
26 Citations1979Chaichan Sangdee, Donald N. Franz
All four drugs enhanced transmission by both NE and 5-HT, but their relative selectivities for the two transmitters differed markedly and were complementary, support those of previous studies based on less direct methods for assessing inhibition of amine reuptake by tricyclic antidepressants.
Psychiatry and Clinical NeurosciencesClinical Evaluation of 5-Hydroxy-L-Tryptophan as an Antidepressant Drug
19 Citations1978Teruo Nakajima, Yoshio Kudo +1 more
Analysis of General Improvement Rating in the various subtypzs of depressive symptoms indicated that endogenous depression and involutional or senile depression were the preferable indication of 5‐hydroxy‐L‐tryptophan loading.
Comprehensive PsychiatryThe position of biological psychiatry among the psychiatric disciplines
13 Citations1971H. M. van Praag
Psychiatry and Clinical NeurosciencesMeasurement of 5–Hydroxyindole Compounds During L-5–HTP Treatment in Depressed Patients
10 Citations1976Saburo Takahashi, Ryo Takahashi +2 more
Clinical response to L‐5–HTP treatment appeared to have some correlation with the biochemical measures in the depressed patients, that is, non‐responders exhibited significantly lower excretion levels of 5–HT and 5–HIAA in urine, and lower plasma levels of 4–HT than responders.
Comprehensive PsychiatryPsychopsychiatry: Can psychosocial factors cause psychiatric disorders?
10 Citations1979H. M. van Praag