Serotonin, Serotonin Genetics(TPH2) and Emotion and Interference Processing

Not Applicable

• Conditions: Healthy
• Interventions: Drug: ATD treatment; Drug: placebo treatment

• Registration Number: NCT03549182
• Lead Sponsor: University of Electronic Science and Technology of China

Brief Summary

The study aims to explore whether acute tryptophan depletion can affect the emotion and interference processing whether this effect is moderated by the TPH2 genotype

Detailed Description

Based on previous studies suggesting that serotonin, a neurotransmitter, is associated with social \& emotional behavior, including emotional reactivity and emotion regulation, the present study aims to explore effects of acute tryptophan depletion (ATD) on emotion processing and emotional interference processing within a randomized double-blind, with-subject, placebo-controlled pharmaco-fMRI experiment. To further examine the potential moderating effects of the genetic makeup of the serotonin system the present study will include a pharmacogenetics imaging approach. Given that TPH2 is the key regulator of the serotonergic signaling pathway, we therefore assessed whether such the effects of tryptophan depletion vary according to the TPH2 genotype. To this end, healthy male TPH2-GG or TPH2-TT carriers will be recruited and will receive ATD (100g) and placebo (102.3g) in a within subject design. To control for potential effects of pre-medication personality traits as well as effects of medicines on mood, subjects will be administered pre-treatment assessing relevant personality traits and post-treatment assessments of mood.

Study Timeline

• Study Start: 2017-03-01
• Study First Submitted: 2018-02-05
• Study First Submitted QC: 2018-06-05
• Study First Posted: 2018-06-07
• Status Verified: 2020-12
• Last Update Submitted: 2020-12-20
• Last Update Posted: 2020-12-22
• Primary Completion: 2021-06-01
• Study Completion: 2021-12-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Male
• Target Recruitment: 50

Inclusion Criteria

• Healthy subjects without past or current psychiatric or neurological disorders
• Right-handedness

Exclusion Criteria

• History of head injury;
• Medical or psychiatric illness.
• High blood pressure, general cardio-vascular alterations
• History of drug or alcohol abuse or addiction.
• Allergy against medications or general strong allergies
• Sleep disorders.
• Visual or motor impairments

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
male TPH2-TTcarriers with placebo then ATD group	placebo treatment	male TPH2-TT carriers will first receive placebo,then will receive ATD at least 5 weeks later.
male TPH2-GG carriers with ATD then placebo group	ATD treatment	male TPH2-GG carriers will first receive ATD, then will receive placebo at least 5 weeks later.
male TPH2-GG carriers with ATD then placebo group	placebo treatment	male TPH2-GG carriers will first receive ATD, then will receive placebo at least 5 weeks later.
male TPH2-GG carriers with placebo then ATD group	ATD treatment	male TPH2-GG carriers will first receive placebo, then will receive ATD at least 5 weeks later.
male TPH2-GG carriers with placebo then ATD group	placebo treatment	male TPH2-GG carriers will first receive placebo, then will receive ATD at least 5 weeks later.
male TPH2-TTcarriers with ATD then placebo group	ATD treatment	male TPH2-TT carriers will first receive ATD, then will receive placebo at least 5 weeks later.
male TPH2-TTcarriers with ATD then placebo group	placebo treatment	male TPH2-TT carriers will first receive ATD, then will receive placebo at least 5 weeks later.
male TPH2-TTcarriers with placebo then ATD group	ATD treatment	male TPH2-TT carriers will first receive placebo,then will receive ATD at least 5 weeks later.

Primary Outcome Measures

Name	Time	Method
Neural processing during emotion processing as assessed via fMRI	5-6h after administration of ATD, or placebo	Subjects will undergo a validated emotional face paradigm. To assess genotype x ATD interaction effects on neural emotional reactivity effects of ATD depletion on the corresponding neural activity will be compared between the TPH2 genotype groups.
Neural processing during interference processing as assessed via fMRI	5-6h after administration of ATD, or placebo	Subjects will undergo a validated cognitive-emotional interference paradigm. To assess genotype x ATD interaction effects on neural interference control effects of ATD depletion on the corresponding neural activity will be compared between the TPH2 genotype groups.
Neural processing during the resting state as assessed via fMRI	5-6h after administration of ATD, or placebo	Subjects will undergo a validated resting state assessment. To assess genotype x ATD interaction effects on intrinsic brain activity in the emotion and interreference related neural networks effects of ATD depletion on the corresponding neural activity will be compared between the TPH2 genotype groups.

Secondary Outcome Measures

Name	Time	Method
Behavioral interference performance	5-6h after administration of ATD, or placebo	Subjects will undergo a emotion-cognition interference paradigm. To assess genotype x ATD interaction effects on behavioral indices of interference (congruent vs incongruent trials) behavioral performance (accuracy/reaction time) effects of ATD depletion on the corresponding behavioral indices will be compared between the TPH2 genotype groups.

Trial Locations

Locations (1)

School of Life Science and Technology; 🇨🇳 Chengdu, Sichuan, China