Mood, Serotonin and Social Interaction

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.

Study Overview

• Status: Completed
• Conditions: Mood; Social Behavior
• Intervention / Treatment: Dietary supplement: tryptophan depletion

Detailed Description

see summary

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • University Center Psychiatry

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: tryptophan depletion first day; tryptophan depletion on the first day. on the other day participants receive placebo.	Dietary supplement: tryptophan depletion; 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
EXPERIMENTAL: tryptophan depletion on day 2; tryptophan depletion on the second day. on the first day participants receive placebo.	Dietary supplement: tryptophan depletion; 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

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serotonin transporter polymorphism	From one of the blood samples collected we will isolate whole blood for DNA extraction in order to analyse the serotonin transporter polymorphism	1 day

Collaborators and Investigators

• Sponsor: University of Groningen
• Investigators: Principal Investigator: Marije aan het Rot, Dr., University of Groningen

Publications and helpful links

General Publications

• Hogenelst K, Schoevers RA, Kema IP, Sweep FC, aan het Rot M. Empathic accuracy and oxytocin after tryptophan depletion in adults at risk for depression. Psychopharmacology (Berl). 2016 Jan;233(1):111-20. doi: 10.1007/s00213-015-4093-9.

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (ACTUAL): March 1, 2014
• Study Completion (ACTUAL): March 1, 2014

Study Registration Dates

• First Submitted: January 24, 2014
• First Submitted That Met QC Criteria: January 29, 2014
• First Posted (ESTIMATE): January 31, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): January 30, 2015
• Last Update Submitted That Met QC Criteria: January 29, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: mood; empathy; prosody; mimicry; emotional reactivity
• Additional Relevant MeSH Terms: Psychotropic Drugs; Antidepressive Agents; Antidepressive Agents, Second-Generation; Tryptophan
• Other Study ID Numbers: NL451-09-013