Effects of tryptophan depletion on memory, attention and executive functions: A systematic review

Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands.
Neuroscience & Biobehavioral Reviews (Impact Factor: 8.8). 07/2009; 33(6):926-52. DOI: 10.1016/j.neubiorev.2009.03.006
Source: PubMed


The serotonergic system is implicated in the regulation of mood and cognition. Acute tryptophan depletion (ATD) is an experimental procedure for lowering central serotonin levels. Here, the effects of ATD on psychomotor processing, declarative memory, working memory, executive functions and attention are discussed. The most robust finding is that ATD impairs the consolidation of episodic memory for verbal information. Semantic memory appears to be unaffected by ATD although a limited variety of tasks examined effects in this domain. Similarly, evidence suggests ATD does not influence verbal, spatial and affective working memory. Most studies investigating effects on executive functions have produced non-specific or negative findings. In terms of attention, ATD either does not affect or may improve focused attention and ATD likely does not impact sustained and divided attention or attentional set-shifting. Although ATD is known to affect mood in certain vulnerable populations, the effects of ATD on cognition in non-vulnerable participants are independent of mood changes. Suggestions for future directions and implications for psychiatric illnesses are discussed.

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    • "Serotonin (5-HT) system has been consistently implicated in cognitive functions such as memory as well as cognitive flexibility that refers primarily to different dimensions of executive functioning and attention (for review, see Schmitt et al. (2006)). 5-HT system may be particularly important for verbal memory as 5-HT depletion robustly impairs verbal memory consolidation (Helmbold et al., 2013; Mendelsohn et al., 2009) and carriers of the S-allele in the 5-HT transporter promoter region perform worse in verbal memory task (Zilles et al., 2012). The serotonin 5-HT 1A receptor may have crucial role at conveying these effects, as both 5-HT 1A receptor agonists and partial agonists impair verbal memory functions (Riedel et al., 2002; Wingen et al., 2007; Yasuno et al., 2003; for review, see Meneses and Perez-Garcia (2007)). "
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    ABSTRACT: The serotonin 5-HT1A receptor is a putative drug development target in disorders with cognitive and in particular memory deficits. However, previous human positron emission tomography (PET) studies on 5-HT1A receptor binding and memory functions have yielded discrepant results. We explored the association between verbal memory and 5-HT1A receptor binding in 24 healthy subjects (14 male, 10 female, aged 18–41 years). The cognitive tests included the Wechsler Memory Scale-Revised (WMS-R), Wechsler Adult Intelligence Scale-Revised (WAIS-R) and Wisconsin Card Sorting Test (WCST). 5-HT1A receptor binding was measured with PET and the radioligand [carbonyl-11C]WAY-100635, which was quantified with the gold standard method based on kinetic modeling using arterial blood samples. We found that global 5-HT1A receptor binding was positively correlated with measures of verbal memory, such that subjects who had higher receptor binding tended to have better verbal memory than subjects who had lower receptor binding. Regional analyses suggested significant correlations in multiple neocortical brain regions and the raphe nuclei. We did not find significant correlations between 5-HT1A receptor binding and executive functions as measured with WCST. We conclude that neocortical as well as raphe 5-HT1A receptors are involved in verbal memory function in man.
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    • ", Hughes et al . , 2003 ; Mendelsohn , Riedel , & Sambeth , 2009 ) . Furthermore , ATD is a pharmacological proce - dure that reduces serotonin to extremely low levels that would not normally occur and would therefore have limited applicabil - ity to understanding how modestly lowered levels of serotonin or any other neurotransmitter are related to self - regulatory fatigue . "
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    • "The afferent connections of the vagus nerve provide direct projections to many of the modulatory regions of the brain that have been implicated in executive control and motivation (Ruffoli et al., 2011) and electronic vagal nerve stimulation affects the release of norepinephrine and serotonin in rats (Dorr and Debonnel, 2006). Thus, further investigation into noradrenergic and serotonergic mechanisms is warranted and may ultimately lead to a more comprehensive understanding of self-regulatory depletion and cognitive fatigue, the latter of which has already been strongly linked to serotonergic depletion by researchers who have studied the effects of tryptophan depletion (the amino acid precursor to serotonin) on cognitive fatigue (Mendelsohn et al., 2009). For dogs, the present research has implications regarding alternative means of replenishment. "
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