Tryptophan depletion in SSRI-recovered depressed outpatients

Spillmann, Maya; Does, Willem Van der; Rankin, Meridith A.; Vuolo, Rachel D.; Alpert, Jonathan E.; Nierenberg, Andrew A.; Rosenbaum, Jerrold F.; Hayden, Douglas; Schoenfeld, David; Fava, Maurizio

doi:10.1007/s002130000669

Cited by 67 publications

(49 citation statements)

References 17 publications

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“…Moreover, this paradigm produces, within the same time frame as that used in the present study, a resurgence of depressive symptoms in patients previously ameliorated by their antidepressant drug regimen (Delgado et al 1990(Delgado et al , 1999Bremner et al 1997). Most importantly, it can produce a recurrence of depressive symptoms in remitted depressed patients who are no longer taking antidepressant drugs (Smith et al 1997;Moreno et al 2000;Spillmann et al 2001). Consequently, the tryptophan depletion was likely sufficient to attenuate 5-HT transmission in the brain of subjects studied in the present experiments.…”

Section: Discussionmentioning

confidence: 58%

Serotonin 1A Receptor Activation and Hypothermia in Humans Lack of Evidence for a Presynaptic Mediation

Blier

Seletti

Gilbert

et al. 2002

Neuropsychopharmacology

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The hypothermia produced by 5-HT 1A 1A receptors are located both on the cell body of 5-HT neurons and on postsynaptic neurons throughout the central nervous system. On 5-HT neurons, 5-HT 1A receptors mediate a negative feedback influence on firing activity. When overactivated by an excess amount of 5-HT, or by an exogenous agonist, they slow down the pacemaker activity leading to a decreased firing rate of 5-HT neurons (Aghajanian and Lakoski 1984;Blier and de Montigny 1987). As 5-HT release is proportional to firing rate, the excess activation of these 5-HT 1A autoreceptors generally results in a decrease of 5-HT release in projecting structures (see Rueter et al. Gainesville, FL 32610, Tel.: 352-392-3681, Fax : 352-392-2579, E-mail : blier@psych.med.ufl.edu Received May 11, 2001 revised January 16, 2002; accepted February 20, 2002. Online publication: 2/27/02 at www.acnp.org/citations/ Npp022702253. 302 P. Blier et al. N EUROPSYCHOPHARMACOLOGY 2002 -VOL . 27 , NO . 2 1997). The postsynaptic 5-HT 1A receptors, particularly abundant in the limbic system, commonly exert an inhibitory function on neuronal activity as well. Therefore, the net effect of the systemic administration of a 5-HT 1A receptor agonist on 5-HT 1A signal transfer in postsynaptic areas represents a composite of decreased 5-HT release, resulting from 5-HT 1A autoreceptor activation, and direct occupation of the postsynaptic 5-HT 1A receptors.Although it is well established that neuroendocrine responses, such as growth hormone and adenocorticotropic hormone release, produced by systemic administration of 5-HT 1A agonists are mediated by postsynaptic 5-HT 1A receptors (Van de Kar et al. 1985;Gilbert et al. 1988;Pan and Gilbert 1992), there has been controversy with respect to the hypothermia resulting from this pharmacological challenge. The very first study examining the pre-versus postsynaptic mediation of the hypothermia clearly indicated that this response was produced by postsynaptic 5-HT 1A receptors (Hjörth 1985). Indeed, this initial study clearly showed that the hypothermic response to the prototypical 5-HT 1A agonist 8-OH-DPAT was not attenuated, but even enhanced in rats pretreated daily for 3 days with the 5-HT synthesis inhibitor parachlorophenylalanine (PCPA). Subsequently, identical results were obtained by another group of investigators using 2-day injections of a higher dose of PCPA (Goodwin et al. 1987). When their PCPA treatment was prolonged, however, for 14 days, despite producing its maximal effect on 5-HT levels after the first 3 days, the 8-OH-DPATinduced hypothermia was dampened and the conclusion of a presynaptic mediation of this phenomenon was made. From then on, several studies carried out in laboratory animals and humans used the 5-HT 1A -induced hypothermia to assess the responsiveness of the 5-HT 1A autoreceptor in different disease states and following administration of various types of psychotropic drugs. Although the majority of studies (Hutson et al. 1987;O'Connell et al. 1992;Hillegaart 1991;Mill...

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Section: Discussionmentioning

confidence: 58%

Serotonin 1A Receptor Activation and Hypothermia in Humans Lack of Evidence for a Presynaptic Mediation

Blier

Seletti

Gilbert

et al. 2002

Neuropsychopharmacology

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“…There is evidence to indicate that a threshold exists that needs to be exceeded before behavioral effects occur. 379,380 Van der Does 379 reviewed several ATD studies and suggests that the threshold for possible mood effects to occur lies somewhere around a 60% reduction of free plasma TRP. In a study comparing high and low dose ATD in remitted depressed patients, Booij et al 381 reported impaired processing of positive information in all and return of depressive symptoms in some of the participants in the high depletion group (80-90% depletion of plasma TRP levels).…”

Section: Depletion/atdmentioning

confidence: 99%

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

et al. 2006

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In recent years, the term serotonergic vulnerability (SV) has been used in scientific literature, but so far it has not been explicitly defined. This review article attempts to elucidate the SV concept. SV can be defined as increased sensitivity to natural or experimental alterations of the serotonergic (5-HTergic) system. Several factors that may disrupt the 5-HTergic system and hence contribute to SV are discussed, including genetic factors, female gender, personality characteristics, several types of stress and drug use. It is explained that SV can be demonstrated by means of manipulations of the 5-HTergic system, such as 5-HT challenges or acute tryptophan depletion (ATD). Results of 5-HT challenge studies and ATD studies are discussed in terms of their implications for the concept of SV. A model is proposed in which a combination of various factors that may compromise 5-HT functioning in one person can result in depression or other 5-HT-related pathology. By manipulating 5-HT levels, in particular with ATD, vulnerable subjects may be identified before pathology initiates, providing the opportunity to take preventive action. Although it is not likely that this model applies to all cases of depression, or is able to identify all vulnerable subjects, the strength of the model is that it may enable identification of vulnerable subjects before the 5-HT related pathology occurs. Molecular Psychiatry ( Keywords: serotonin; mood disorders; stress; genetics; sex; tryptophan Involvement of serotonin in depressionMood disorders are one of the most prevalent forms of mental illness. 1 According to the DSM-IV, the lifetime risk for major depressive disorder is between 10 and 25% for women and between 5 and 12% for men. 2 Depression has been studied intensively during the last few decades, but the psychological and neurobiological determinants of depression have not yet been precisely defined. Although several factors are known to contribute to the etiology of depression, it is not clear how these factors cause depression, and why some subjects become depressed while others remain unaffected. In terms of biological factors in the etiology of depression, there are several hypotheses. These include neurotransmitter dysfunctions (serotonin, 5-HT; dopamine, DA; norepinephrine, NE); dysregulations in hypothalamic-pituitary-adrenal (HPA) axis activity; and immune system imbalance. The aim of this article is not to discuss all of these hypotheses in detail, but to evaluate the role that serotonin may play within these hypothesized mechanisms.It is widely accepted that diminished serotonergic (5-HTergic) function is involved in the onset and course of depression. 3,4 The 5-HTergic system is a large and complex system. Although nearly all cell bodies of 5-HTergic neurons are located in the raphe nuclei in the brain stem, the axons of these neurons innervate almost the entire brain. The actions of 5-HT are mediated by 16 types and subtypes of receptors. 5 As the 5-HTergic system is assumed to be a modulatory system, the exact func...

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“…Further research support, however, has since become available. [25][26][27][28] Although each of these studies comprised a relatively small number of patients, the replications are important because of the negative findings mentioned above.…”

Section: Acute Tryptophan Depletionmentioning

confidence: 99%

Monoamine depletion in psychiatric and healthy populations: review

2003

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A number of techniques temporarily lower the functioning of monoamines: acute tryptophan depletion (ATD), alpha-methyl-para-tyrosine (AMPT) and acute phenylalanine/tyrosine depletion (APTD). This paper reviews the results of monoamine depletion studies in humans for the period 1966 until December 2002. The evidence suggests that all three interventions are specific, in terms of their short-term effects on one or two neurotransmitter systems, rather than on brain protein metabolism in general. The AMPT procedure is somewhat less specific, affecting both the dopamine and norepinephrine systems. The behavioral effects of ATD and AMPT are remarkably similar. Neither procedure has an immediate effect on the symptoms of depressed patients; however, both induce transient depressive symptoms in some remitted depressed patients. The magnitude of the effects, response rate and quality of response are also comparable. APTD has not been studied in recovered major depressive patients. Despite the similarities, the effects are distinctive in that ATD affects a subgroup of recently remitted patients treated with serotonergic medications, whereas AMPT affects recently remitted patients treated with noradrenergic medications. The evidence also suggests that ATD and APTD affect different cognitive functions, in particular different memory systems. Few studies investigated cognitive effects of the procedures in patients. Patients who are in remission for longer may also be vulnerable to ATD and AMPT, but the relationship with prior treatment is much weaker. For these patients, individual vulnerability markers are the more important determinants of depressive response, making these techniques potentially useful models of vulnerability to depression. Molecular Psychiatry (2003) 8, 951-973.

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Tryptophan depletion in SSRI-recovered depressed outpatients

Cited by 67 publications

References 17 publications

Serotonin 1A Receptor Activation and Hypothermia in Humans Lack of Evidence for a Presynaptic Mediation

Serotonin 1A Receptor Activation and Hypothermia in Humans Lack of Evidence for a Presynaptic Mediation

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

Monoamine depletion in psychiatric and healthy populations: review

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