scholarly journals Oxytocinergic modulation of threat-specific amygdala sensitization in humans is critically mediated by serotonergic mechanisms

2020 ◽  
Author(s):  
Congcong Liu ◽  
Chunmei Lan ◽  
Keshuang Li ◽  
Feng Zhou ◽  
Shuxia Yao ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Acute Tryptophan Depletion ◽  
Placebo Control ◽  
Tryptophan Depletion ◽  
Social Emotional ◽  
Double Blind ◽  
Link Type ◽  
Parallel Group ◽  
Emotional Effects

AbstractBackgroundOverarching conceptualizations propose that the complex social-emotional effects of oxytocin (OXT) in humans are partly mediated by interactions with other neurotransmitter systems. Recent animal models suggest that the anxiolytic effects of OXT are critically mediated by the serotonin (5-HT) system, yet direct evidence in humans is lacking.MethodsTo determine the role of 5-HT in OXT-induced attenuation of amygdala threat reactivity and sensitization/ desensitization, we conducted a parallel-group randomized placebo-controlled double-blind experiment during which n = 121 healthy subjects underwent a transient decrease in 5-HT signaling via acute tryptophan depletion (ATD, TRYP-) or the corresponding placebo-control protocols before the administration of intranasal OXT or placebo intranasal spray, respectively. Mean and repetition-dependent changes in threat-specific amygdala reactivity towards threatening stimuli (angry faces) as assessed by fMRI served as the primary outcome.ResultsNo treatment main or interaction effects on amygdala threat reactivity were observed, yet OXT switched bilateral amygdala threat sensitization to desensitization and this effect was significantly attenuated during decreased central 5-HT signaling via pretreatment with TRYP-.ConclusionsThe present findings provide the first evidence for a role of OXT in threat-specific amygdala desensitization in humans and suggest that these effects are critically mediated by the 5-HT system. OXT may have a therapeutic potential to facilitate amygdala desensitization and adjunct up-regulation of 5-HT neurotransmission may facilitate OXT’s anxiolytic potential.The trial was preregistered on clinicaltrials.gov (https://clinicaltrials.gov/ct2/show/NCT03426176, ID NCT03426176)

scholarly journals Oxytocinergic modulation of stress-associated amygdala-hippocampus pathways in humans is specially mediated by serotonergic mechanisms

2021 ◽  
Author(s):  
Chunmei Lan ◽  
Congcong Liu ◽  
Keshunag Li ◽  
Zhiying Zhao ◽  
Yina Ma ◽  
...  
Keyword(s):  
Resting State ◽  
Resting State Fmri ◽  
Interactive Effects ◽  
Acute Tryptophan Depletion ◽  
Placebo Control ◽  
Tryptophan Depletion ◽  
Double Blind ◽  
Fmri Study ◽  
Parallel Group ◽  
Pre Treatment

Background: The hypothalamic neuropeptide oxytocin (OXT) may exert anxiolytic and stress-reducing actions via modulatory effects on amygdala circuits. Animal models and initial findings in humans suggest that some of these effects are mediated by interactions with other neurotransmitter systems, in particular the serotonin (5-HT) system. Against this background, the present pharmacological resting state fMRI study aimed at determining whether effects of OXT on stress-associated amygdala intrinsic networks are mediated by 5-HT. Methods: We employed a randomized placebo-controlled double-blind parallel-group pharmacological fMRI resting state experiment during which n = 112 healthy male participants underwent a transient decrease in 5-HT signaling via acute tryptophan depletion (ATD+) or the corresponding placebo-control protocols (ATD-) before the administration of intranasal OXT or placebo intranasal spray, respectively. Results: OXT and 5-HT modulation exerted interactive effects on the coupling of the left amygdala with the ipsilateral hippocampus and adjacent midbrain. OXT increased intrinsic coupling in this pathway, while this effect of OXT was significantly attenuated during transiently decreased central serotonergic signaling induced via ATD+. In the absence of OXT or 5-HT modulation this pathway was associated with self-reported stress perception in everyday life, while an OXT-induced modulation of this pathway was following ATD- pre-treatment. Conclusions: Together, the findings provide first evidence that effects of OXT on stress-associated amygdala-hippocampal-midbrain pathways are critically mediated by the 5-HT system in men.

scholarly journals Effect of acute tryptophan depletion on CO2-induced anxiety in patients with panic disorder and normal volunteers

2000 ◽  
Vol 176 (2) ◽  
pp. 182-188 ◽  
Author(s):  
H. E. J. Miller ◽  
J. F. W. Deakin ◽  
I. M. Anderson
Keyword(s):  
Panic Disorder ◽  
Panic Attacks ◽  
Acute Tryptophan Depletion ◽  
Tryptophan Depletion ◽  
Double Blind ◽  
Normal Volunteers ◽  
Plasma Tryptophan ◽  
Drug Free ◽  
Normal Controls

BackgroundUncertainties remain about the role of serotonin in the aetiology and treatment of panic disorder.AimsTo investigate the effect of reducing brain serotonin function on anxiety at rest, and following 5% CO2 provocation in normal controls and patients with panic disorder.MethodTwenty drug-free patients with DSM–III–R panic disorder and 19 controls received a tryptophan-free amino acid drink on one occasion and a control drink on the other in a double-blind, balanced protocol. 5% CO2 was given as a panic challenge after 270 minutes.ResultsPlasma tryptophan fell by more than 80% both patients and controls after the tryptophan-free drink. Tryptophan depletion did not alter resting anxiety. In patients alone, tryptophan depletion caused a greater anxiogenic response and an increased rate of panic attacks (9 v. 2, P<0.05) after 5% CO2 challenge. No normal volunteers panicked.ConclusionsSerotonin may directly modulate panic anxiety in patients with panic disorder. This may underlie the efficacy of serotonergic antidepressants in treating panic disorder.

scholarly journals Evaluating the role of serotonin in hot flashes after breast cancer using acute tryptophan depletion

2009 ◽  
Vol 16 (4) ◽  
pp. 644-652 ◽  
Author(s):  
Janet S. Carpenter ◽  
Menggang Yu ◽  
Jingwei Wu ◽  
Diane Von Ah ◽  
Jennifer Milata ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hot Flashes ◽  
Acute Tryptophan Depletion ◽  
Tryptophan Depletion

scholarly journals The role of G-CSF in recurrent implantation failure: A randomized double blind placebo control trial

2016 ◽  
Vol 14 (12) ◽  
pp. 737-742 ◽  
Author(s):  
Fatemeh Davari-tanha ◽  
Ensieh Shahrokh Tehraninejad ◽  
Mohadese Ghazi ◽  
Zahra Shahraki ◽  
◽  
...  
Keyword(s):  
Placebo Control Trial ◽  
Placebo Control ◽  
Implantation Failure ◽  
Recurrent Implantation Failure ◽  
Double Blind ◽  
Double Blind Placebo

scholarly journals Randomized trial of preladenant, given as monotherapy, in patients with early Parkinson disease

Neurology ◽  
2017 ◽  
Vol 88 (23) ◽  
pp. 2198-2206 ◽  
Author(s):  
Fabrizio Stocchi ◽  
Olivier Rascol ◽  
Robert A. Hauser ◽  
Susan Huyck ◽  
Anjela Tzontcheva ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Active Control ◽  
Rating Scale ◽  
Double Blind ◽  
Clinical Trial Registration ◽  
Link Type ◽  
Parallel Group ◽  
Number Of Patients ◽  
Disease Rating ◽  
Post Hoc

Objective:To evaluate the adenosine 2a receptor antagonist preladenant as a nondopaminergic drug for the treatment of Parkinson disease (PD) when given as monotherapy.Methods:This was a randomized, 26-week, placebo- and active-controlled, parallel-group, multicenter, double-blind trial conducted in adults diagnosed with PD for <5 years who were not yet receiving l-dopa or dopamine agonists. Patients with a Unified Parkinson’s Disease Rating Scale (UPDRS) part 3 (motor function) score ≥10 and Hoehn & Yahr score ≤3 were randomized 1:1:1:1:1 to preladenant 2, 5, or 10 mg twice daily, rasagiline 1 mg (active-control) once daily, or placebo. The primary endpoint was the change from baseline at week 26 in the sum of UPDRS parts 2 (activities of daily living) and 3 scores (UPDRS2+3).Results:The number of patients treated was 1,007. Neither preladenant nor rasagiline was superior to placebo after 26 weeks. The differences vs placebo (95% confidence interval) in UPDRS2+3 scores (with a negative difference indicating improvement vs placebo) were preladenant 2 mg = 2.60 (0.86, 4.30), preladenant 5 mg = 1.30 (−0.41, 2.94), preladenant 10 mg = 0.40 (−1.29, 2.11), and rasagiline 1 mg = 0.30 (−1.35, 2.03). Post hoc analyses did not identify a single causal factor that could explain the finding of a failed trial. Preladenant was generally well-tolerated with few patients discontinuing due to adverse events (preladenant 7%, rasagiline 3%, placebo 4%).Conclusions:No evidence supporting the efficacy of preladenant as monotherapy was observed in this phase 3 trial. The lack of efficacy of the active control rasagiline makes it difficult to interpret the results.Clinical trial registration:Clinicaltrials.gov: NCT01155479.Classification of evidence:This study provides Class I evidence that for patients with early PD, preladenant is not effective as monotherapy at the doses studied (2, 5, 10 mg).

scholarly journals Meta-analysis of double-blind placebo control trials evaluating the role of coenzyme Q10 on semen parameters

2018 ◽  
Vol 110 (4) ◽  
pp. e167-e168 ◽  
Author(s):  
A. Agarwal ◽  
A. Sharma ◽  
K. Master ◽  
R. Sharma ◽  
R. Henkel
Keyword(s):  
Coenzyme Q10 ◽  
Meta Analysis ◽  
Semen Parameters ◽  
Placebo Control ◽  
Double Blind ◽  
Double Blind Placebo

Effects of acute tryptophan depletion on cognitive function in Alzheimer's disease and in the healthy elderly

2002 ◽  
Vol 33 (1) ◽  
pp. 41-49 ◽  
Author(s):  
R. J. PORTER ◽  
B. S. LUNN ◽  
J. T. O'BRIEN
Keyword(s):  
Cognitive Function ◽  
Rating Scales ◽  
Senile Dementia ◽  
Specific Effect ◽  
Acute Tryptophan Depletion ◽  
Elderly Subjects ◽  
Tryptophan Depletion ◽  
Emotional Symptoms ◽  
Double Blind ◽  
Healthy Elderly

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.

Dependence of Phonatory Effort on Hydration Level

1994 ◽  
Vol 37 (5) ◽  
pp. 1001-1007 ◽  
Author(s):  
Katherine Verdolini ◽  
Ingo R. Titze ◽  
Ann Fennell
Keyword(s):  
Control Treatment ◽  
Placebo Control ◽  
Double Blind ◽  
Hydration Level ◽  
Phonation Threshold Pressure ◽  
Perceived Phonatory Effort ◽  
Direct Measures ◽  
Psychological Measure ◽  
Hydration And Dehydration

In this study, a double-blind placebo-controlled approach was used to assess the relation between hydration level and phonatory effort. Twelve adult, untrained voice users with normal voices participated as subjects. Each subject received a 4-hour hydration treatment, a 4-hour dehydration treatment, and a 4-hour placebo (control) treatment. Following each treatment, phonatory effort was measured with a physiological measure, phonation threshold pressure (PTP), and with a psychological measure, direct magnitude estimation of perceived phonatory effort (DMEPPE). Summarizing the results across these measures, the findings indicated an inverse relation between phonatory effort and hydration level, but primarily for high-pitched phonation tasks. The findings for PTPs replicated those from an earlier study conducted without double-blind experimental manipulations (Verdolini-Marston, Titze, & Druker, 1990). Theoretical discussion focuses on the possible role of vocal fold tissue viscosity for hydration and dehydration effects, although direct measures of tissue viscosity are lacking.

scholarly journals Effects of Acute Tryptophan Depletion on Three Different Types of Behavioral Impulsivity

2010 ◽  
Vol 3 ◽  
pp. IJTR.S4317 ◽  
Author(s):  
Donald M. Dougherty ◽  
Dawn M. Richard ◽  
Lisa M. James ◽  
Charles W. Mathias
Keyword(s):  
Amino Acid ◽  
Response Inhibition ◽  
Acute Tryptophan Depletion ◽  
Future Research ◽  
Placebo Control ◽  
Tryptophan Depletion ◽  
Biological Processes ◽  
Response Initiation ◽  
Different Types ◽  
Behavioral Impulsivity

Introduction While central nervous system serotonin has been implicated in a variety of problematic impulsive behaviors, biological manipulation of brain serotonin using acute tryptophan depletion for studying changes in impulsive behavior has received little attention. Methods Using identical treatment conditions, we examined the effects of reduced serotonin synthesis for each of three matched groups using acute tryptophan depletion. Thirty healthy men and women (ages 18–45) were assigned to perform one of three tasks assessing different types of behavioral impulsivity: response initiation, response inhibition, and consequence sensitivity ( N = 90). Participants completed two experimental days during which each consumed either a tryptophan-depletion or balanced-placebo amino-acid formulation and completed 5 sessions of their respective tasks at 0.25 h before and 1.5, 4.0, 5.0, and 6.0 h after beverage consumption. Results During peak effectiveness (5.0 h to 6.0 h following amino-acid consumption), depletion produced selective differences dependent on the type of impulsivity being tested. Specifically, relative to baseline testing (pre-depletion), response initiation impulsivity was significantly increased during the peak effects of depletion. And, when compared to placebo control, both response initiation and consequence sensitivity impulsivity were increased during the peak effects of depletion. Conclusion Though response initiation and consequence sensitivity impulsivity were affected by tryptophan depletion, response inhibition impulsivity was not, suggesting that other biological processes may underlie this specific component of impulsivity. Future research in other populations or using different pharmacological agents is warranted to further examine the biological processes underlying these components of impulsivity.

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