Mood, Serotonin and Social Interaction

Study Overview
=================
Brief Summary
-----------------
Rationale: Major depressive disorder (MDD) is a psychiatric disorder whose onset, severity, and duration are influenced by interpersonal factors. The serotonin system is known to influence MDD risk. Recent research has suggested that serotonin may also play a role in regulating social behaviour. Therefore, it would be interesting to study the role of serotonin in responses to social stimuli in individuals at risk for MDD. Objective: This project aims to study how changes in serotonin alter interpersonal functioning in adults with or without a first degree family member diagnosed with MDD. The primary goal is to investigate the effect of experimentally lowered brain serotonin levels on empathic accuracy. Secondary goals are to determine how this manipulation influences verbal and non-verbal communication, cardiovascular function in a social context, and mood. An exploratory goal is to investigate how these outcomes are related to genes thought to be involved in MDD.

Detailed Description
-----------------
see summary

Official Title
-----------------
Mood, Serotonin and Social Interaction

Conditions
-----------------
Mood, Social Behavior

Intervention / Treatment
-----------------
* Dietary Supplement: tryptophan depletion


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18 to 65 yrs At least one first-degree family member with MDD, Family History (FH) positive, or no first and -second degree family members with MDD, FH negative Willingness to cooperate, to sign written informed consent Exclusion Criteria: Any current or past Diagnostic and Statistical Manual (DSM) IV Axis I mood disorder, anxiety disorder, psychotic disorder, eating disorder, or somatoform disorder as determined by Structured Clinical Interview for DSM interview Any current substance use disorder Any past substance dependence Ongoing medical treatment for a chronic disease, particularly cancer, gastrointestinal disease, phenylketonuria, diabetes, cardiovascular disease, or disease of the liver or kidneys Not speaking Dutch fluently Current or past use of neuroleptics, sedative drugs, antidepressants etc. On test days, a positive urine test for drugs of abuse For women, initiation of hormonal contraceptive treatments 3 months prior to screening, or a positive urine test for pregnancy on test days

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tryptophan depletion first day<br>tryptophan depletion on the first day. on the other day participants receive placebo. | Dietary Supplement: tryptophan depletion<br>* tryptophan depletion involves the ingestion of an amino acid mixture that is devoid of tryptophan. on the other day participants receive placebo, being the same mixture but including tryptophan<br>|
| Experimental: tryptophan depletion on day 2<br>tryptophan depletion on the second day. on the first day participants receive placebo. | Dietary Supplement: tryptophan depletion<br>* tryptophan depletion involves the ingestion of an amino acid mixture that is devoid of tryptophan. on the other day participants receive placebo, being the same mixture but including tryptophan<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Empathic Accuracy | Empathic Accuracy is assessed with a computer task, approximately 6 hrs after completion of the amino acid mixture | 45 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Behavioral mimicry | Behavioral mimicry is assessed in two experiments. In the first experiment, mimicry of a person in a video is assessed. In a second experiment mimicry is assessed in response to the investigators mannerisms | 10 minutes | 
| Emotional Prosody (EP) | EP is assessed in two experiments. In the first experiment, EP is assessed in response to a video. In a second experiment EP is assessed in a dyad with the investigator. | 10 minutes | 
| blood | blood is analysed for levels of tryptophan, oxytocin and cortisol | 10 minutes | 
| heart rate variability | hrv is measured in response to emotional video clips | 1 hour | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
mood, empathy, mimicry, emotional reactivity, prosody