Tryptophan modulation and cognition (original) (raw)
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Tryptophan, mood, and cognitive function
Brain, Behavior, and Immunity, 2002
In separate experiments we investigated the duration of the effects of acute tryptophan depletion (ATD) on mood and cognition. The results showed that ATDÕs effects consist of lowering of mood only in subjects with a family history of unipolar depression. A specific impairment of memory consolidation was seen in all subjects. In subjects without any vulnerability for mood disorders, performance on so-called Ôfrontal tasks,Õ measuring higher attentional functions tended to improve after ATD. The effects of ATD on mood and cognition were manifest as long as biochemical indices of low tryptophan remained low. In conclusion, ATD is a model for impairment of memory, next to being a model of mood disorders in vulnerable subjects. Moreover, ATD could be used as a challenge to demonstrate individual vulnerability of the serotonergic system.
Relationship of brain tryptophan and serotonin in improving cognitive performance in rats
Pakistan journal of pharmaceutical sciences, 2006
Brain function can be affected by the availability of dietary precursors of neurotransmitters. The diet induced increase in tryptophan (TRP) availability has been shown to increase brain serotonin synthesis and various related behaviors. Evidence shows that TRP and serotonin (5HT; 5 Hydroxytryptamine) play a significant role in memory function. Enhanced brain serotonin activity has been shown to improve cognitive performance in animals and human whereas decreasing brain 5HT levels by acute TRP depletion has been shown to impair cognition. A number of methods have been used for the assessment of memory in animals. In the present study, the radial arm maze and the passive avoidance was used for the assessment of memory in rats following long-term TRP administration. TRP at doses of 50 and 100 mg/kg body weight was orally administered for 6 weeks. The present study shows a significant improvement in memory of rats following both doses of tryptophan. Plasma TRP, brain TRP, 5HT and 5 hyd...
Cognitive changes after acute tryptophan depletion: what can they tell us?
Psychological Medicine, 2004
Serotonin (5-hydroxytryptamine, 5-HT) is known to play a role in a wide variety of functions including: mood, anxiety, sleep, aggression, sexual function and cognitive function. In the past decade, the sudden interest in acute amino acid depletion paradigms has stimulated the interest in studying the function of 5-HT in man in vivo. In particular, investigating the association of experimentally lowered 5-HT with cognition by measuring the influence of acute tryptophan depletion (ATD) on performance, and in some cases applying ATD as a challenge test using cognition as disease surrogate marker, have recently become popular. The crucial questions, ‘what can this method tell us about cognitive function in health and disease?’ and ‘what can ATD-induced cognitive changes tell us about health and disease?’ can only be answered after first considering basic assumptions about the method. These pertain to the derived questions, ‘is ATD a serotonergic manipulation?’, ‘is the placebo used in A...
Current Pharmaceutical Design, 2010
Acute tryptophan depletion (ATD), a method to temporarily lower central serotonin levels, has been used to study the functioning of the serotonergic system. Relatively recent studies that examined the effects of ATD on brain activation associated with cognitive and emotional processing in healthy volunteers are reviewed. An overview of the findings in healthy volunteers is important for the interpretation of the effect of ATD on brain activation in patients with an affective disorder, such as major depression. These studies show that during response control and negative feedback processing ATD modulates the BOLD response in the inferior/orbitofrontal cortex, the anterior cingulate cortex and the dorsomedial prefrontal cortex. During emotional processing, it is consistently found that ATD modulates the BOLD response in the amygdala. These brain regions also show abnormal activation in depressed patients.
The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP), 2007
Polymorphism at the serotonin transporter linked polymorphic region (5-HTTLPR) has been associated with neuroticism, increased risk for affective disorders and greater vulnerability to mood change following serotonin (5-HT) depletion. The aim of the present study was to investigate whether the cognitive effects of 5-HT depletion were differentially affected by genotype at the 5-HTTLPR polymorphism, using neuropsychological measures of memory and attention. We utilized the acute tryptophan depletion (ATD) technique to temporarily reduce 5-HT synthesis in two groups of healthy volunteers pre-selected on the basis of 5-HTTLPR genotype, 15 of the ll genotype and 15 of the ss genotype, in a double-blind, placebo-controlled crossover design. As expected, ATD resulted in a robust reduction in plasma tryptophan concentration in both genotype groups. However, the genotype groups differed in terms of the effect of ATD on cognitive performance. The ss genotype group showed impaired verbal reca...
Neuropsychopharmacology, 2003
Cognitive impairment has repeatedly been described in bipolar disorders (BD). Serotonin (5-hydroxytryptophan; 5-HT) is possibly involved in these cognitive processes, more particularly in executive functions, learning, memory, and attention. The aim of this study was to investigate serotonergic vulnerability and its relation to cognitive functioning in healthy first-degree relatives of BD patients. We investigated the effects of an intravenous (i.v.) tryptophan (Trp) challenge and placebo on cognitive performance in 30 healthy firstdegree relatives of bipolar patients (FH) and 15 matched controls in a double-blind crossover design. A distinction was made between relatives of type I BD patients (FH I) and type II BD patients (FH II). Performances on planning, memory, attention, and psychomotor tasks were assessed 3 h after Trp infusion. After Trp, planning and attention were impaired in FH subjects but not in controls. Independent of Trp, FH subjects showed cognitive deficits on memory, focused and divided attention, and psychomotor performance. FH I subjects showed more pronounced cognitive impairments then FH II and controls. In all groups, Trp impaired memory and psychomotor performance significantly. In conclusions, cognitive deficits in FH following Trp may reflect a central 5-HT vulnerability in frontal brain areas. Independent of Trp, cognitive deficits in FH provide evidence for a trait marker for BD.
Psychopharmacology, 1987
In a previous study we found that a tryptophandeficient amino acid mixture, designed to lower tissue tryptophan and thus brain 5-hydroxytryptamine (5HT) levels, caused a rapid (5 h) lowering of mood in normal males. Because of the importance of this evidence indicating a direct causal connection between low 5HT and low mood, we have now investigated other possible explanations for the mood lowering effect. Research strongly supports the involvement of environmental setting and cognition in the production and experience of emotions. Therefore we investigated how these factors might influence the mood-lowering effects of tryptophan depletion. In an instructional manipulation subjects were either supplied or not supplied with information designed to account for any possible peripheral sensations that might be related to depressive affect. In an environmental manipulation subjects were exposed either to a supportive and comfortable atmosphere (positive environment), or an unrewarding and unstimulating environment (negative environment). In the control group, which received a balanced amino acid mixture, the positive and negative environments had the expected effects on the scores of the Multiple Affect Adjective Checklist, thus indicating the effectiveness of these procedures. In the tryptophan depletion group neither the instructional nor the environmental manipulation had any influence on the mood lowering effect. It may be that tryptophan depletion lowers mood in normal males because low 5HT influences mood directly rather than via cognitive processes. Our data strongly support the idea that 5HT exerts an effect on mood and that low 5HT may, in some patients, be an important factor contributing to the etiology of clinical depression.
Tryptophan depletion and its implications for psychiatry
British Journal of Psychiatry, 2001
BackgroundOver the past 10 years the technique of tryptophan depletion has been used increasingly as a tool for studying brain serotonergic systems.AimsTo review the technique of tryptophan depletion and its current status as a tool for investigating psychiatric disorders.MethodSystematic review of preclinical and clinical studies.ResultsTryptophan depletion produces a marked reduction in plasma tryptophan and consequently brain serotonin (5-HT) synthesis and release. In healthy volunteers the effects of tryptophan depletion are influenced by the characteristics of the subjects and include some mood lowering, some memory impairment and an increase in aggression. In patients with depression tryptophan depletion tends to result in no worsening of depression in untreated subjects but a relapse in those who have responded to antidepressants (particularly serotonergic agents). In panic disorder the results are similar.ConclusionsThe findings that tryptophan depletion produces a relapse o...