scholarly journals Serotonin depletion impairs both Pavlovian and instrumental reversal learning in healthy humans

2020 ◽  
Author(s):  
Jonathan W. Kanen ◽  
Annemieke M. Apergis-Schoute ◽  
Robyn Yellowlees ◽  
Frederique E. Arntz ◽  
Febe E. van der Flier ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Psychiatric Disorders ◽  
Reversal Learning ◽  
Emotional Reactions ◽  
Tryptophan Depletion ◽  
Double Blind ◽  
Experimental Animals ◽  
Serotonin Depletion ◽  
Healthy Humans ◽  
Aversive Processing

AbstractSerotonin is implicated in aversive processing and updating responses to changing environmental circumstances. Optimising behaviour to maximise reward and minimise punishment may require shifting strategies upon encountering new situations. Likewise, emotional reactions to threats are critical for survival yet must be modified as danger shifts from one source to another. Whilst numerous psychiatric disorders are characterised by behavioural and emotional inflexibility, few studies have examined the contribution of serotonin in humans. We modelled both processes in two independent experiments (N = 97), using instrumental and aversive Pavlovian reversal learning paradigms, respectively. Upon depleting the serotonin precursor tryptophan – in a double-blind randomised placebo-controlled design – healthy volunteers showed impairments in updating both behaviour and emotion to reflect changing contingencies. Reversal deficits in each domain, furthermore, were correlated with the extent of tryptophan depletion. These results translate findings in experimental animals to humans and have implications for the neurochemical basis of cognitive inflexibility.

scholarly journals Serotonin depletion impairs both Pavlovian and instrumental reversal learning in healthy humans

2021 ◽  
Author(s):  
Jonathan W. Kanen ◽  
Annemieke M. Apergis-Schoute ◽  
Robyn Yellowlees ◽  
Fréderique E. Arntz ◽  
Febe E. van der Flier ◽  
...  
Keyword(s):  
Reversal Learning ◽  
Skin Conductance Response ◽  
Tryptophan Depletion ◽  
Trial And Error ◽  
Double Blind ◽  
Autonomic Responses ◽  
Stimulus Response ◽  
Healthy Humans ◽  
Threatening Stimulus ◽  
Reversal Phase

AbstractSerotonin is involved in updating responses to changing environmental circumstances. Optimising behaviour to maximise reward and minimise punishment may require shifting strategies upon encountering new situations. Likewise, autonomic responses to threats are critical for survival yet must be modified as danger shifts from one source to another. Whilst numerous psychiatric disorders are characterised by behavioural and autonomic inflexibility, few studies have examined the contribution of serotonin in humans. We modelled both processes, respectively, in two independent experiments (N = 97). Experiment 1 assessed instrumental (stimulus-response-outcome) reversal learning whereby individuals learned through trial and error which action was most optimal for obtaining reward or avoiding punishment initially, and the contingencies subsequently reversed serially. Experiment 2 examined Pavlovian (stimulus-outcome) reversal learning assessed by the skin conductance response: one innately threatening stimulus predicted receipt of an uncomfortable electric shock and another did not; these contingencies swapped in a reversal phase. Upon depleting the serotonin precursor tryptophan—in a double-blind randomised placebo-controlled design—healthy volunteers showed impairments in updating both actions and autonomic responses to reflect changing contingencies. Reversal deficits in each domain, furthermore, were correlated with the extent of tryptophan depletion. Initial Pavlovian conditioning, moreover, which involved innately threatening stimuli, was potentiated by depletion. These results translate findings in experimental animals to humans and have implications for the neurochemical basis of cognitive inflexibility.

scholarly journals Probabilistic reversal learning under acute tryptophan depletion in healthy humans: a conventional analysis

2020 ◽  
Vol 34 (5) ◽  
pp. 580-583
Author(s):  
Jonathan W Kanen ◽  
Frederique E Arntz ◽  
Robyn Yellowlees ◽  
Rudolf N Cardinal ◽  
Annabel Price ◽  
...  
Keyword(s):  
Reversal Learning ◽  
Negative Feedback ◽  
Acute Tryptophan Depletion ◽  
Tryptophan Depletion ◽  
Serotonin Synthesis ◽  
Male And Female ◽  
Healthy Humans ◽  
Enhanced Sensitivity ◽  
Conventional Analysis ◽  
Probabilistic Reversal Learning

The involvement of serotonin in responses to negative feedback is well established. Acute serotonin reuptake inhibition has enhanced sensitivity to negative feedback (SNF), modelled by behaviour in probabilistic reversal learning (PRL) paradigms. Whilst experiments employing acute tryptophan depletion (ATD) in humans, to reduce serotonin synthesis, have shown no clear effect on SNF, sample sizes have been small. We studied a large sample of healthy volunteers, male and female, and found ATD had no effect on core behavioural measures in PRL. These results indicate that ATD effects can differ from other manipulations of serotonin expected to have a parallel or opposing action.

Rapid Tryptophan Depletion Improves Decision-Making Cognition in Healthy Humans without Affecting Reversal Learning or Set Shifting

2005 ◽  
Vol 31 (7) ◽  
pp. 1519-1525 ◽  
Author(s):  
Peter S Talbot ◽  
David R Watson ◽  
Suzanne L Barrett ◽  
Stephen J Cooper
Keyword(s):  
Decision Making ◽  
Reversal Learning ◽  
Tryptophan Depletion ◽  
Set Shifting ◽  
Healthy Humans

scholarly journals Neuroticism as a predictor of mood change: The effects of tryptophan depletion

2002 ◽  
Vol 181 (3) ◽  
pp. 242-247 ◽  
Author(s):  
Mary E. Stewart ◽  
I.J. Deary ◽  
K. P. Ebmeier
Keyword(s):  
Cognitive Function ◽  
Family History ◽  
Healthy Volunteers ◽  
Acute Tryptophan Depletion ◽  
Tryptophan Depletion ◽  
Mood Change ◽  
Double Blind ◽  
History Of ◽  
Mood And Cognition ◽  
Double Blind Crossover Study

BackgroundAcute tryptophan depletion (ATD) results in a transient lowering of mood in patients recovered from depression and in healthy volunteers with a family history of affective disorders. The personality trait of neuroticism is strongly associated with depression.AimsTo assess whether neuroticism predicts mood change in response to ATD in healthy volunteers.MethodHealthy volunteers who scored at the top and bottom fifth percentiles of neuroticism scores (17 and 15 respectively) were selected. In a double-blind, crossover study they received a tryptophan-free or a control drink. Mood and cognition were assessed.ResultsNeuroticism did not predict the amount of mood change following ATD but did moderate performance on the verbal fluency test. A family history of affective disorder (n=5) predicted mood change but not cognitive function following ATD.ConclusionsNeuroticism moderates aspects of cognitive function, but in this study it was not strongly related with mood change via serotonin.

Effects of Neurapas® balance on sleep EEG, cognitive performance and mood: A double-blind randomised cross-over study in healthy volunteers

2005 ◽  
Vol 38 (05) ◽  
Author(s):  
M Giesler ◽  
A Thum ◽  
A Haag ◽  
A Wartenberg-Demandt ◽  
G McGregor ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Cognitive Performance ◽  
Sleep Eeg ◽  
Double Blind

scholarly journals Relative absorption of silicon from different formulations of dietary supplements: a pilot randomized, double-blind, crossover post-prandial study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
N. Boqué ◽  
R. M. Valls ◽  
A. Pedret ◽  
F. Puiggrós ◽  
L. Arola ◽  
...  
Keyword(s):  
Dietary Supplements ◽  
Inductively Coupled Plasma ◽  
Aloe Vera ◽  
Emission Spectrometry ◽  
Orthosilicic Acid ◽  
Post Dose ◽  
Double Blind ◽  
Gold Standard Method ◽  
Healthy Humans ◽  
Relative Absorption

AbstractThe purpose of the present study was to compare the relative absorption of a new powder presentation of silicon (Si) as orthosilicic acid with maltodextrin (Orgono Powder) compared to usual Si liquid presentations as orthosilicic acid with Equisetum arvense and Rosmarinus officinalis (G5 Siliplant) and orthosilicic acid with aloe vera (G7 Aloe). All dietary supplements were administered at the same Si oral dose (21.6 mg) in a randomized, double-blind, crossover post-prandial study conducted in 5 healthy men. Urine was collected at baseline and over the 6-h post-dose period in 2 separate 3-h collections for the analysis of Si concentration, which was conducted by inductively coupled plasma optical emission spectrometry as the gold standard method. No significant differences in total urinary Si excretion were found after the intake of these 3 dietary supplements; 34.6%, 32.4% and 27.2% of the ingested Si from G7 Aloe, G5 Siliplant and Orgono Powder, respectively, was excreted in urine over the 6-h follow-up period. The 3 different oral Si formulations tested, in powder and liquid presentations, provide highly bioavailable Si and present an equivalent relative absorption in healthy humans.

506 Samelisant: Baseline Characteristics from a Phase 2 Study Evaluating Efficacy and Safety in Patients with Narcolepsy

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A199-A199
Author(s):  
Ramakrishna Nirogi ◽  
Jyothsna Ravula ◽  
Pradeep Jayarajan ◽  
Satish Jetta ◽  
Gopinadh Bhyrapuneni ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Demographic Data ◽  
Fixed Ratio ◽  
Study Drug ◽  
Eligibility Criteria ◽  
Double Blind ◽  
Healthy Humans ◽  
Parallel Group ◽  
Secondary Endpoints ◽  
Baseline Characteristics

Abstract Introduction histamine H3 receptor (H3R) antagonists/ inverse agonists increase histaminergic neurotransmission and offer a therapeutic option for the treatment of narcolepsy. Samelisant (SUVN-G3031) is a potent and selective H3R inverse agonist exhibited selectivity over 70 other targets. Samelisant showed wake-promoting and anticataplectic effects in orexin knockout mice suggesting its potential therapeutic utility in the treatment of EDS and cataplexy associated with narcolepsy. Safety and tolerability studies in animals and healthy humans suggested a favorable risk/benefit profile. Methods The current study is a 2 week treatment, multicenter, double-blind, placebo controlled, parallel-group study in patients with Narcolepsy with or without Cataplexy. Eligibility criteria include age between 18 to 50 years old, an ESS score of ≥ 12; and mean MWT time of < 12 minutes and a confirm diagnosis of narcolepsy as per ICSD-3. Further, the randomization will be stratified according to type of narcolepsy (Type-1 or Type-2). Each subject will receive either placebo or study drug once daily for 2 weeks in a fixed ratio of 1:1:1. The primary efficacy endpoint is change in maintenance of wakefulness test (MWT) score from baseline to week 2. Key secondary endpoints include change from baseline to week 2 in ESS and an improvement in CGI-S scores. Safety will be monitored by medical monitor and by an independent data safety monitoring committee. Baseline clinical and demographic data for the currently enrolled study is summarized descriptively. Since the study is blinded, a breakdown of baseline characteristics by treatment group will not be available until after completion. Results As of data cutoff date of Dec 20, 2020, a total of 54 subjects were completed in the study. The median age of subjects was 30 years (range: 18 - 50 years) with mean BMI of 28.6 (range: 18.3 - 43.1 kg/m2). Overall, 74% of subjects were female and 83% were Caucasian. Mean (SD) baseline values of MWT and ESS are 5.65 (3.5) and 16.7 (2.5), respectively. Conclusion Baseline characteristics are consistent with the general narcolepsy population. The study is currently enrolling the subjects with Narcolepsy with or without Cataplexy, and the Data readout is expected in the second half of 2021. Support (if any):

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