scholarly journals Effects of Acute Tryptophan Depletion on Human Taste Perception

2020 ◽  
Author(s):  
Sharon A Smith ◽  
Paula D Trotter ◽  
Francis P McGlone ◽  
Susannah C Walker

Abstract Taste perception has been reported to vary with changes in affective state. Distortions of taste perception, including blunted recognition thresholds, intensity and hedonic ratings have been identified in those suffering from depressive disorders. Serotonin is a key neurotransmitter implicated in the aetiology of anxiety and depression; systemic and peripheral manipulations of serotonin signalling have previously been shown to modulate taste detection. However, the specific effects of central serotonin function on taste processing have not been widely investigated. Here, in a double-blind placebo-controlled study, acute tryptophan depletion was used to investigate the effect of reduced central serotonin function on taste perception. 25 female participants aged 18-28 attended the laboratory on 2 occasions at least 1 week apart. On one visit they received a tryptophan depleting drink and on the other a control drink was administered. Approximately 6 hours after drink consumption they completed a taste perception task which measured detection thresholds and supra-threshold perceptions of the intensity and pleasantness of four basic tastes (sweet, sour, bitter and salt). While acutely reducing central levels of serotonin had no effect on the detection thresholds of sweet, bitter or sour tastes it significantly enhanced detection of salt. For supra-threshold stimuli, acutely reduced serotonin levels significantly enhanced the perceived intensity of both bitter and sour tastes and blunted pleasantness ratings of bitter quinine. These findings show manipulation of central serotonin levels can modulate taste perception and are consistent with previous reports that depletion of central serotonin levels enhances neural and behavioural responsiveness to aversive signals.

Author(s):  
Mallikarjuna Rao I. ◽  
Usha Kiran Prayaga ◽  
Dharma Rao Uppada ◽  
Ramachandra Rao E. ◽  
B. L. Kudagi

Background: The SSRIs being used as 1st line therapy in treatment of depression have delayed therapeutic effect which makes the patient vulnerable to an increased risk of suicide and decreased adherence to the treatment and will prematurely discontinue the therapy. The present study was conducted to evaluate if low dose mirtazapine-escitalopram combination therapy has any add on benefit over monotherapy with escitalopram.Methods: In a single-centered, comparative study involving patients with depression attending the out-patient after screening and exclusion, 60 eligible patients were randomly assigned to receive tablet mirtazapine 7.5 mg plus tablet escitalopram 10 mg intervention or tablet escitalopram 10 mg plus placebo intervention in a double-blind 6-week treatment phase. The primary outcome measure was the change in the 17-item Hamilton Depression Rating Scale (HDRS) and Montgomery-Asberg Depression Rating Scale (MADRS) score from baseline. Participants were evaluated at baseline, 1st, 2nd,4th and 6th week. Results were analyzed using Chi-Square test for adverse effects and independent t-test analysis for efficacy parameter.Results: In the analysis of results at 6th week the numbers of patients achieved remission in mirtazapine group are more with a p-value of 0.018 which is significant and the numbers of responders in mirtazapine group are also more which is statistically significant on chi-square test. There is no significant difference was observed between the two groups with reference to occurrence of adverse effect.Conclusions: Adding low dose mirtazapine has an added benefit in terms of efficacy and getting remission early with more number of responders in the treatment of major depression.


2002 ◽  
Vol 33 (1) ◽  
pp. 41-49 ◽  
Author(s):  
R. J. PORTER ◽  
B. S. LUNN ◽  
J. T. O'BRIEN

Background. The cholinergic system is profoundly impaired in senile dementia of Alzheimer type (SDAT) and replacement therapy produces only modest clinical benefits. The serotonergic system is also impaired and may contribute both to cognitive and non-cognitive symptoms in SDAT. To investigate this further we assessed the effects of lowering brain serotonin using the technique of acute tryptophan depletion on cognitive function in patients with SDAT and in age matched control subjects.Method. Sixteen patients with probable SDAT and 17 healthy elderly subjects received two amino acid drinks in a within subject, double-blind, placebo-controlled, counterbalanced, crossover design. One of the drinks was nutritionally balanced and contained tryptophan (placebo), the other was identical but contained no tryptophan. A battery of detailed neuropsychological tests was performed between 4 and 6 h after the drink. Mood rating scales and other ratings of behavioural and emotional symptoms were also performed on both occasions.Results. Acute tryptophan depletion resulted in impairment on tasks of working memory in both groups. There was no group specific effect. Female SDAT subjects performed better on a task of pattern recognition during acute tryptophan depletion compared with placebo. There were no changes in behavioural symptoms during acute tryptophan depletion in either group.Conclusion. Compromised serotonergic function may be an important contributor to cognitive decline in SDAT and in ageing. Strategies targeting specific 5HT receptors may be helpful in SDAT.


2004 ◽  
Vol 10 (4) ◽  
pp. 434-441 ◽  
Author(s):  
Derick T Wade ◽  
Petra Makela ◽  
Philip Robson ◽  
Heather House ◽  
Cynthia Bateman

The objective was to determine whether a cannabis-based medicinal extract (CBME) benefits a range of symptoms due to multiple sclerosis (MS). A parallel group, double-blind, randomized, placebo-controlled study was undertaken in three centres, recruiting 160 outpatients with MS experiencing significant problems from at least one of the following: spasticity, spasms, bladder problems, tremor or pain. The interventions were oromucosal sprays of matched placebo, or whole plant CBME containing equal amounts of delta-9- tetrahydrocannabinol (THC) and cannabidiol (CBD) at a dose of 2.5- 120 mg of each daily, in divided doses. The primary outcome measure was a Visual Analogue Scale (VAS) score for each patient’s most troublesome symptom. Additional measures included VAS scores of other symptoms, and measures of disability, cognition, mood, sleep and fatigue. Following CBME the primary symptom score reduced from mean (SE) 74.36 (11.1) to 48.89 (22.0) following CBME and from 74.31 (12.5) to 54.79 (26.3) following placebo [ns]. Spasticity VAS scores were significantly reduced by CBME (Sativex) in comparison with placebo (P- 0.001). There were no significant adverse effects on cognition or mood and intoxication was generally mild.


1979 ◽  
Vol 7 (1) ◽  
pp. 7-18 ◽  
Author(s):  
Ryo Takahashi ◽  
Akira Sakuma ◽  
Toshio Hara ◽  
Hajime Kazamatsuri ◽  
Atsuyoshi Mori ◽  
...  

A multi-clinic double-blind controlled study on amoxapine in comparison with imipramine, using the WHO Schedule for a Standard Assessment of Patients with Depressive Disorders, was performed and the data were analyzed with 111 patients. The assessment of severity of illness and overall improvement indicated clearly the superiority of the antidepressive effect of amoxapine to that of imipramine. The onset of antidepressive effect of amoxapine was clearly more rapid than that of imipramine, and in more than half of the patients in the amoxapine group the improvement was seen within four days following the drug administration, Amoxapine was superior to imipramine in terms of safety and usefulness. The side-effects due to amoxapine appeared less frequently and were less serious than with imipramine. The difference between amoxapine and imipramine was especially remarkable for hypotensive effect. The antidepressive effect of amoxapine was superior to that of imipramine for almost all symptoms and signs. Amoxapine displayed an especially remarkable effect on psychomotor retardation, depressive feeling, anxiety and tension, somatic complaints and sleep disturbance.


2020 ◽  
Vol 9 (12) ◽  
pp. 4103
Author(s):  
Francina Fonseca ◽  
Joan-Ignasi Mestre-Pintó ◽  
Àlex Gómez-Gómez ◽  
Diana Martinez-Sanvisens ◽  
Rocío Rodríguez-Minguela ◽  
...  

Major depression disorder (MDD) is the most prevalent psychiatric comorbid condition in cocaine use disorder (CUD). The comorbid MDD might be primary-MDD (CUD-primary-MDD) or cocaine-induced MDD (CUD-induced-MDD), and their accurate diagnoses and treatment is a challenge for improving prognoses. This study aimed to assess the tryptophan/serotonin (Trp/5-HT) system with the acute tryptophan depletion test (ATD), and the kynurenine pathway in subjects with CUD-primary-MDD, CUD-induced-MDD, MDD and healthy controls. The ATD was performed with a randomized, double-blind, crossover, and placebo-controlled design. Markers of enzymatic activity of indoleamine 2,3-dioxygenase/tryptophan 2,3-dioxygenase, kynurenine aminotransferase (KAT) and kynureninase were also established. Following ATD, we observed a decrease in Trp levels in all groups. Comparison between CUD-induced-MDD and MDD revealed significant differences in 5-HT plasma concentrations (512 + 332 ng/mL vs. 107 + 127 ng/mL, p = 0.039) and the Kyn/5-HT ratio (11 + 15 vs. 112 + 136; p = 0.012), whereas there were no differences between CUD-primary-MDD and MDD. Effect size coefficients show a gradient for all targeted markers (d range 0.72–1.67). Results suggest different pathogenesis for CUD-induced-MDD, with lower participation of the tryptophan system, probably more related to other neurotransmitter pathways and accordingly suggesting the need for a different pharmacological treatment approach.


2016 ◽  
Vol 28 (9) ◽  
pp. 1487-1491 ◽  
Author(s):  
Janet L. Mace ◽  
Richard J. Porter ◽  
John C. Dalrymple-Alford ◽  
Chris Collins ◽  
Tim J. Anderson

ABSTRACTBackground:Studies using acute tryptophan depletion (ATD) to examine the effects of a rapid reduction in serotonin function have shown a reduction in global cognitive status during ATD in Alzheimer's disease (AD) and Parkinson's disease (PD). Based on the severe cholinergic loss evident in dementia with Lewy bodies (DLB) and Parkinson's disease and dementia (PDD), we predicted that a reduction of global cognitive status during ATD would be greater in these conditions than in AD.Methods:Patients having DLB or PDD underwent ATD in a double-blind, placebo-controlled, randomized, counterbalanced, crossover design.Results:While the study intended to test 20 patients, the protocol was poorly tolerated and terminated after six patients attempted, but only four patients – three with DLB and one with PDD – completed the protocol. The Modified Mini-Mental State Examination (3MSE) score was reduced in all three DLB patients and unchanged in the PDD and dementia patient during ATD compared with placebo.Conclusions:This reduction in global cognitive function and the poor tolerability may fit with the hypothesis that people with dementia with Lewy bodies have sensitivity to the effects of reduced serotonin function.


eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Tobias U Hauser ◽  
Micah Allen ◽  
Nina Purg ◽  
Michael Moutoussis ◽  
Geraint Rees ◽  
...  

Impairments in metacognition, the ability to accurately report one’s performance, are common in patients with psychiatric disorders, where a putative neuromodulatory dysregulation provides the rationale for pharmacological interventions. Previously, we have shown how unexpected arousal modulates metacognition (Allen et al., 2016). Here, we report a double-blind, placebo-controlled, study that examined specific effects of noradrenaline and dopamine on both metacognition and perceptual decision making. Signal theoretic analysis of a global motion discrimination task with adaptive performance staircasing revealed that noradrenergic blockade (40 mg propranolol) significantly increased metacognitive performance (type-II area under the curve, AUROC2), but had no impact on perceptual decision making performance. Blockade of dopamine D2/3 receptors (400 mg amisulpride) had no effect on either metacognition or perceptual decision making. Our study is the first to show a pharmacological enhancement of metacognitive performance, in the absence of any effect on perceptual decision making. This enhancement points to a regulatory role for noradrenergic neurotransmission in perceptual metacognition.


2011 ◽  
Vol 26 (S2) ◽  
pp. 619-619 ◽  
Author(s):  
E. Corruble ◽  
C. Bélaidi ◽  
G.M. Goodwin

The novel antidepressant agomelatine is a MT1/MT2 receptor agonist and a 5HT2c receptor antagonist, whose efficacy is demonstrated in Major Depressive Disorder (MDD) (1). In an international 24-week double-blind randomized controlled study, the effects of agomelatine 25–50 mg/d (n = 164) were compared to those of escitalopram 10-20 mg/d (n = 160) on satisfaction about sleep (Visual Analogic Scale), depressive symptoms (Hamilton Depression Rating Scale (HAM-D)) and emotions in a subset of 45 patients having completed the Oxford Depression Questionnaire (2).Both drugs improved depressive symptoms (mean decrease in HAM-D score from baseline: -19.9 with agomelatine and -19.2 with escitalopram; percentage of remitters: 69.6% with agomelatine and 63.1% with escitalopram, LOCF endpoint) and the satisfaction about sleep. Interestingly, the wellness feeling on waking was more improved with agomelatine as compared to escitalopram (p = 0.025), indicating a better alertness on waking with agomelatine than escitalopram.Moreover, emotional blunting was less frequent with agomelatine as compared to escitalopram: 28% on agomelatine vs 60% on escitalopram felt that their emotions lacked intensity with a trend to statistical significance (p = 0.063) and 16% of patients on agomelatine vs 53% on escitalopram felt that things that they cared about before illness did not seem important any more (p = 0.024). Finally, less patients withdrew due to emergent adverse events with agomelatine (4.3%) as compared to escitalopram (10.6%), (p = 0.029). To conclude, this study shows some potential clinical advantages of agomelatine as compared to escitalopram in the long term treatment of MDD.


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