Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: a meta-analysis of monoamine depletion studies.
ABSTRACT Dysfunction in the monoamine systems of serotonin (5-HT), norepinephrine (NE) and dopamine (DA) may causally be related to major depressive disorder (MDD). Monoamine depletion studies investigate the direct effects of monoamines on mood. Acute tryptophan depletion (ATD) or para-chlorophenylalanine (PCPA) deplete 5-HT, acute phenylalanine/tyrosine depletion (APTD) or alpha-methyl-para-tyrosine (AMPT) deplete NE/DA. Available depletion studies found conflicting results in heterogeneous populations: healthy controls, patients with previous MDD in remission and patients suffering from MDD. The decrease in mood after 5-HT and NE/DA depletion in humans is reviewed and quantified. Systematic search of MEDLINE and EMBASE (1966-October 2006) and cross-references was carried out. Randomized studies applying ATD, PCPA, APTD or AMPT vs control depletion were included. Pooling of results by meta-analyses was stratified for studied population and design of the study (within or between subjects). Seventy-three ATD, 2 PCPA, 10 APTD and 8 AMPT studies were identified of which 45 ATD and 8 APTD studies could be meta-analyzed. 5-HT or NE/DA depletion did not decrease mood in healthy controls. 5-HT or NE/DA depletion slightly lowered mood in healthy controls with a family history of MDD. In drug-free patients with MDD in remission, a moderate mood decrease was found for ATD, without an effect of APTD. ATD induced relapse in patients with MDD in remission who used serotonergic antidepressants. In conclusion, monoamine depletion studies demonstrate decreased mood in subjects with a family history of MDD and in drug-free patients with MDD in remission, but do not decrease mood in healthy humans. Although depletion studies usefully investigate the etiological link of 5-HT and NE with MDD, they fail to demonstrate a causal relation. They presumably clarify a vulnerability trait to become depressed. Directions for further investigation of this vulnerability trait are proposed.
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ABSTRACT: Acute tryptophan depletion (ATD) studies indicate that low serotonin can lower mood and also increase aggression, although results vary somewhat between studies with similar participants. Lowering of mood after ATD is related to the susceptibility of the study participants to clinical depression, and some participants show no effect on mood. This indicates that low serotonin can contribute to lowered mood, but cannot-by itself-cause lowered mood, unless other unknown systems interact with serotonin to lower mood. Studies using tryptophan supplementation demonstrate that increased serotonin can decrease quarrelsomeness and increase agreeableness in everyday life. Social interactions that are more agreeable and less quarrelsome are associated with better mood. Thus, serotonin may have direct effects on mood, but may also be able to influence mood through changes in social behaviour. The increased agreeableness and decreased quarrelsomeness resulting from increases in serotonin will help foster congenial relations with others and should help to increase social support. As social support and social isolation have an important relationship with both physical and mental health, more research is needed on the implications of the ability of serotonin to modulate social behaviour for the regulation of mood, and for future physical and mental health.Philosophical Transactions of The Royal Society B Biological Sciences 01/2013; 368(1615):20110375. · 6.40 Impact Factor
Article: The interface between inhibition of descending noradrenergic pain control pathways and negative affects in post-traumatic pain patients.[show abstract] [hide abstract]
ABSTRACT: Animal studies have shown that surgical trauma activates the descending noradrenergic pathway. However, perioperative patients have decreased concentrations of noradrenaline (NA) in the cerebrospinal fluid (CSF). We proposed that the descending monoaminergic pathway is altered in post-traumatic pain patients and that CSF monoamine neurotransmitters may be more closely related to affective symptoms. We investigated the levels of monoamine neurotransmitters and assessed pain in these patients. Patients were divided into a post-traumatic pain group, a pain-free group, a painful labor group, and a pain-free labor group. CSF was collected from all patients, and concentrations of NA, 3-methoxy-4-hydroxyphenylglycol (MHPG), dopamine, homovanillic acid, and 5-hydroxyindoleacetic acid (5-HIAA) were measured by high-performance liquid chromatography. In the post-traumatic pain group, lumbar CSF concentrations of NA and MHPG were significantly decreased (P < 0.01) compared to the control group. The post-traumatic pain group displayed a significant negative correlation between NA and the respective total value of the short form of the McGill pain questionnaire (SF-MPQ), SF-MPQ (affective), and visual analog scale (r = -0.388, r = -0.433, and r = -0.367; P < 0.05). Post-traumatic pain patients demonstrated decreased concentrations of NAin CSF, indicating that descending noradrenergic pain control pathways may be inhibited. NA is more closely related to negative affects in post-traumatic pain patients.Upsala journal of medical sciences 02/2012; 117(3):293-9. · 0.73 Impact Factor
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ABSTRACT: Peroxisome Proliferator-Activated Receptors (PPARs) are a family of nuclear receptors whose activation modulates the gene expression that underlies both the glucid-lipid and the inflammation pathways. While many PPARs agonists have been used for years as medication for metabolic disorders, an increasing attention is being currently dedicated to these drugs for inflammation-related pathologies. Within the psychiatric field, it has recently appeared that inflammatory processes are highly suspected in the pathophysiology of several important disorders, such as schizophrenia and mood disorders. By their anti-inflammatory properties, PPARs might have a disease-modifying action that could help in improving the outcome of patients. Furthermore, recent data suggest that PPARs could also modulate the expression of some neurotransmission factors. Therefore, PPARs may directly modify the information processing, and have a potential symptomatic action on several psychiatric disorders. At last, PPARs action of metabolic regulation could have a role on corrective or even preventive strategies against the metabolic adverse events that are commonly observed with some current psychiatric medications, notably antipsychotics. This triple potential action profile of PPARs modulators is investigated in this article, successively for schizophrenia spectrum disorders and mood disorders. Theoretical involvements of PPARs are also discussed for the treatment of Post-Traumatic Stress Disorder and Personality Disorders. At the time of the emerging concept of psychoneuroimmunology, PPARs open original therapeutic prospects for the psychiatric research.Current drug targets 03/2013; · 3.93 Impact Factor
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TitleDose-escalation in the picture : pharmacological and imaging studies in depression
Faculty Faculty of Medicine
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Dose-escalation in the picture
Pharmacological and Imaging studies in depression
Dose-escalation in the picture
Dose-escalation in the picture
Omslag Ruhe.indd 117-9-2008 15:56:58
DOSE-ESCALATION IN THE PICTURE
PHARMACOLOGICAL AND IMAGING STUDIES IN DEPRESSION
The work described in this thesis was mostly performed at the Academic Medical Center, Program
for Mood Disorders in the Netherlands. The studies were conducted in close collaboration with
the departments of Nuclear Medicine, General Practice, Pharmacology and Pharmacotherapy,
Clinical Epidemiology, Biostatistics and Bioinformatics and Radiology.
Most of the studies in this thesis were financially supported by grants from the Academic Medical
Center (SFA.07.012), the Netherlands Organisation for Health Research and Development
(ZonMw), program Mental Health, education of investigators in mental health (OOG; #100-002-
002), and from the Dutch Brain Foundation (14F06.45).
Additional support for the completion of this thesis was provided by Amicale Facel Holland.
Dose-Escalation in the Picture. Pharmacological and Imaging studies in depression
Thesis, University of Amsterdam, The Netherlands. With a summary in Dutch.
Copyright © 2008, Henricus G. Ruhé, Amstelveen, The Netherlands H.G.Ruhe@AMC.UvA.NL
All rights reserved. No part of this thesis may be reproduced, stored or transmitted in any form or
by any means, without prior permission of the author.
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Dose-Escalation in the Picture
Pharmacological and Imaging studies
ter verkrijging van de graad van doctor
aan de Universiteit van Amsterdam
op gezag van de Rector Magnificus
prof. dr. D.C. van den Boom
ten overstaan van een door het college voor promoties
in het openbaar te verdedigen in de Aula der Universiteit
op woensdag 5 november 2008, te 10:00 uur
Henricus Gerardus Ruhé
geboren te Amsterdam