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

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Influence of Acute Tryptophan Depletion on Emotion and Interference Processing and Potential Moderation by 5HT Genetics (TPH2)

Conditions
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Healthy

Intervention / Treatment
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* Drug: ATD treatment
* Drug: placebo treatment


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: male TPH2-GG carriers with ATD then placebo group<br>male TPH2-GG carriers will first receive ATD, then will receive placebo at least 5 weeks later. | Drug: ATD treatment<br>* oral administration of ATD (100g)(Acute Tryptophan Depletion)<br>Drug: placebo treatment<br>* oral administration of placebo (102.3g)<br>|
| Experimental: male TPH2-GG carriers with placebo then ATD group<br>male TPH2-GG carriers will first receive placebo, then will receive ATD at least 5 weeks later. | Drug: ATD treatment<br>* oral administration of ATD (100g)(Acute Tryptophan Depletion)<br>Drug: placebo treatment<br>* oral administration of placebo (102.3g)<br>|
| Experimental: male TPH2-TTcarriers with ATD then placebo group<br>male TPH2-TT carriers will first receive ATD, then will receive placebo at least 5 weeks later. | Drug: ATD treatment<br>* oral administration of ATD (100g)(Acute Tryptophan Depletion)<br>Drug: placebo treatment<br>* oral administration of placebo (102.3g)<br>|
| Experimental: male TPH2-TTcarriers with placebo then ATD group<br>male TPH2-TT carriers will first receive placebo,then will receive ATD at least 5 weeks later. | Drug: ATD treatment<br>* oral administration of ATD (100g)(Acute Tryptophan Depletion)<br>Drug: placebo treatment<br>* oral administration of placebo (102.3g)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neural processing during emotion processing as assessed via fMRI | 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. | 5-6h after administration of ATD, or placebo | 
| Neural processing during interference processing as assessed via fMRI | 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. | 5-6h after administration of ATD, or placebo | 
| Neural processing during the resting state as assessed via fMRI | 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. | 5-6h after administration of ATD, or placebo | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Behavioral interference performance | 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. | 5-6h after administration of ATD, or placebo | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute tryptophan depletion, tryptophan hydroxylase 2 gene, emotion