Serotonergic‘vulnerability’ in affective disorder: a study of the tryptophan depletion test and relationships between peripheral and central serotonin indexes in citalopram‐responders

Åberg‐Wistedt, Anna; Hasselmark, L.; Stain-Malmgren, Rigmor; Apéria, B.; Kjellman, Bengt; Mathé, Aleksander A.

doi:10.1111/j.1600-0447.1998.tb10017.x

Cited by 47 publications

(37 citation statements)

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“…In essence, serotonergic vulnerability (SV) means that there is a vulnerability or sensitivity to alterations or dysregulations in the 5-HTergic system (based upon references 21,[23][24][25][26][27][28][29][30] ). Thus, the idea is that the 5-HTergic functioning of an individual determines the vulnerability of that individual to develop disorders that are related to 5-HT.…”

Section: -Htergic Vulnerabilitymentioning

confidence: 99%

“…Mood lowering in response to ATD demonstrates individual vulnerability of the 5-HTergic system. 24,[27][28][29][30]373 In currently depressed untreated patients, ATD does not cause any mood-lowering (for review see Maes and Meltzer, 23 Bell et al, 320 Young and Leyton 321 ). However, ATD can cause mood changes in subjects with a personal history of mood disorders.…”

Section: Depletion/atdmentioning

confidence: 99%

“…358 A mood response to ATD appears to be the best way to identify subjects with SV, because this mood response indicates that the 5-HTergic system lacks the ability to compensate for the transient decrease in TRP and 5-HT. ATD has already been described as a way to identify a subgroup of patients with a specific 5-HTergic 'vulnerability' 30 and as a suitable model of vulnerability to depression. 382 ATD causes mood lowering in some populations, but results are generally mixed, and ATD does not cause mood lowering in currently depressed patients.…”

Section: Proposed Model and Conclusionmentioning

confidence: 99%

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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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Section: -Htergic Vulnerabilitymentioning

confidence: 99%

Section: Depletion/atdmentioning

confidence: 99%

Section: Proposed Model and Conclusionmentioning

confidence: 99%

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Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

et al. 2006

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“…In remitted depressed patients, ATD induced depressive symptoms (Smith et al 1997;Aberg-Wistedt et al 1998;Moreno et al 2000). In healthy first-degree relatives of depressed patients, ATD induced a modest lowering of mood, compared with healthy control subjects (Benkelfat et al 1994;Klaassen et al 1999).…”

Section: -Ht Vulnerability In Relatives Of Bipolar Patients 835mentioning

confidence: 99%

Effects of Acute Tryptophan Depletion on Mood and Cortisol Release in First-degree Relatives of Type I and Type II Bipolar Patients and Healthy Matched Controls

Sobczak

Honig

Nicolson

et al. 2002

Neuropsychopharmacology

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Biological vulnerability for bipolar disorders (BD) in relatives of BD patients has not as yet been established. Serotonergic vulnerability was studied, using acute tryptophan depletion (ATD), in healthy first-degree relatives of BD patients and healthy controls. The effects of ATD on mood and cortisol release in 30 healthy adult, lifetime symptom free, unaffected first-degree relatives of BD patients (Family History; FH) were compared with effects in 15 healthy matched controls in a placebocontrolled, double-blind, crossover design. During ATD and placebo, salivary cortisol response was also assessed during a stress-inducing speech task (SIST). First-degree relatives of type II BD patients (FH II) showed an elevation of mood, whereas control subjects and relatives of type I BD patients (FH I) showed a lowering of mood after ATD. ATD was followed by a decrease in cortisol level in both FHIn the pathophysiology of bipolar disorders (BD), several lines of evidence support the hypothesis of an underlying dysfunction of the serotonergic system. Increased platelet serotonin (5-hydroxytryptamine or 5-HT), a lower maximal velocity (Vmax) of 5-HT platelet uptake and decreased central serotonergic neurotransmitter activity, indicated by decreased 5HIAA/5-HT ratios, have been reported in untreated bipolar depressed patients (Wirz Justice and Puhringer 1978; Marazziti et al.1991;Leake et al. 1991;Young et al. 1994). Polymorphism in the 5-HT-transporter, 5-HT receptors and the tryptophan hydroxylase gene have been associated with the pathophysiology of BD (Kunugi et al. 1997;Oruc et al. 1997;Bellivier et al. 1998).Acute tryptophan depletion (ATD) is a direct method to investigate central serotonergic vulnerability (Delgado et al. 1994). In this procedure, a lowering of central 5-HT Vulnerability in Relatives of Bipolar Patients 8355-HT synthesis is accomplished by giving subjects a 50-100 g balanced amino acid-drink (AA-drink), composed of amino acids, including large neutral amino acids (LNAAs: tyrosine, valine, leucine, isoleucine and phenylalanine), and devoid of tryptophan (Trp) (Young 1991). In remitted depressed patients, ATD induced depressive symptoms (Smith et al. 1997;Aberg-Wistedt et al. 1998;Moreno et al. 2000). In healthy first-degree relatives of depressed patients, ATD induced a modest lowering of mood, compared with healthy control subjects (Benkelfat et al. 1994;Klaassen et al. 1999). It thus appears that individuals without prior depressive episodes, but at a genetic risk for depression, may be biologically predisposed to mood-lowering effects of ATD.Until now, little attention has been paid to the effects of ATD in BD, and results are inconsistent . Cappiello et al. (1997) reported a significant increase in manic symptoms in recently remitted (one month) lithium-treated manic patients. In BD patients who were stable for a longer period (1-15 years), ATD did not induce significant mood changes (Benkelfat et al. 1995;Cassidy et al. 1998;Hughes et al. 2000).In BD patients abnormalities in cortisol homeostas...

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“…No mood measures were reported in that study, but chronically high cortisol has frequently been linked to dysphoric mood and clinical depression (Checkley, 1996), although this might relate to dysfunction of brain 5-HT systems as well as the hypothalamic pituitary adrenal axis (Van Praag, 1996). Indeed, high baseline plasma cortisol predicts induction of depression by acute dietary TRP depletion (Åberg-Wistedt et al 1998). By comparison with acute effects, any understanding of mechanisms underlying chronic effects will need to include neurotransmitter and neurohormone receptor adaptation (Huether et al 1998).…”

Section: Effects Of Chronic Dietary Manipulations On Mood and Performmentioning

confidence: 99%

Nutritional influences on cognitive function: mechanisms of susceptibility

Gibson

Green

2002

NRR

119

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The impact of nutritional variation, within populations not overtly malnourished, on cognitive function and arousal is considered. The emphasis is on susceptibility to acute effects of meals and glucose loads, and chronic effects of dieting, on mental performance, and effects of cholesterol and vitamin levels on cognitive impairment. New developments in understanding dietary influences on neurohormonal systems, and their implications for cognition and affect, allow reinterpretation of both earlier and recent findings. Evidence for a detrimental effect of omitting a meal on cognitive performance remains equivocal: from the outset, idiosyncrasy has prevailed. Yet, for young and nutritionally vulnerable children, breakfast is more likely to benefit than hinder performance. For nutrient composition, despite inconsistencies, some cautious predictions can be made. Acutely, carbohydrate-rich-protein-poor meals can be sedating and anxiolytic; by comparison, protein-rich meals may be arousing, improving reaction time but also increasing unfocused vigilance. Fat-rich meals can lead to a decline in alertness, especially where they differ from habitual fat intake. These acute effects may vary with time of day and nutritional status. Chronically, protein-rich diets have been associated with decreased positive and increased negative affect relative to carbohydrate-rich diets. Probable mechanisms include diet-induced changes in monoamine, especially serotoninergic neurotransmitter activity, and functioning of the hypothalamic pituitary adrenal axis. Effects are interpreted in the context of individual traits and susceptibility to challenging, even stressful, tests of performance. Preoccupation with dieting may impair cognition by interfering with working memory capacity, independently of nutritional status. The change in cognitive performance after administration of glucose, and other foods, may depend on the level of sympathetic activation, glucocorticoid secretion, and pancreatic ␤-cell function, rather than simple fuelling

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Serotonergic‘vulnerability’ in affective disorder: a study of the tryptophan depletion test and relationships between peripheral and central serotonin indexes in citalopram‐responders

Cited by 47 publications

References 17 publications

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

Effects of Acute Tryptophan Depletion on Mood and Cortisol Release in First-degree Relatives of Type I and Type II Bipolar Patients and Healthy Matched Controls

Nutritional influences on cognitive function: mechanisms of susceptibility

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