Interaction Between Early Trauma and Odor-induced Dopamine Release (T-ODOR)

Consequence of Early Trauma on Odor Hedonics Appreciation and DOpamine Release

This prospective, double-blind, parallel-group controlled trial aims to investigate the consequence of early trauma on dopamine release evoked by positive valence odors.

Study Overview

• Status: Not yet recruiting
• Conditions: Trauma, Psychological
• Intervention / Treatment: Other: High score at Childhood Trauma Questionnaire.; Other: Low score at Childhood Trauma Questionnaire.

Detailed Description

The occurrence of early trauma has been linked to alterations in the development of emotion regulation circuits and functional brain connectivity (particularly in the dorsolateral prefrontal cortex - DLPFC), the dopaminergic response to stress and an alteration in hedonicity (including olfactory hedonicity), which can lead to the onset of psychiatric disorders such as anxiety or depression.

However, few studies have investigated the influence of early trauma on the release of dopamine (DA) evoked by odors with a positive emotional valence. Yet hedonicity is a key component of olfaction, as a positive odor leads to reinforced behavior in areas such as food intake and social interaction. This reinforcement process is thought to be underpinned by the very close link between the olfactory system (olfactory tubercle), the emotional regulation system (DLPFC) and the reward system (striatum), including the release of DA.

The aim of the study is to investigate the influence of early trauma on DAergic transmission evoked by odorants with a positive emotional valence.

To this end, 30 participants will be recruited and divided into two groups: those with early trauma and those without, according to their score on the Childhood Trauma Questionnaire. They will undergo an MRI-PET scan during which they will be exposed to pleasant odors. Subcortical dopaminergic transmission will be analyzed using the PET activity of [11C]Raclopride (a D2 receptor antagonist).

Investigators hypothesize that early trauma resulting in abnormal cortico-subcortical and cortico-cortical connectivity would lead to a deficit in the hedonic appreciation of a pleasant odor, associated with a reduction in DAergic reactivity evoked in the reward system.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: VERONIQUE VIAL; Phone Number: 0033437915522; Email: veronique.vial@ch-le-vinatier.fr
• Study Contact Backup: Name: FILIPE GALVAO; Phone Number: 0033437915565; Email: filipe.galvao@ch-le-vinatier.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Aged 18 years or older
• Have been selected based on the Childhood Trauma Questionnaire score
• Non-smoker
• Be able to speak and read French
• Sign a consent form before intervention.

Exclusion Criteria:

• A pre-existing condition that affects olfaction including congenital anosmia, upper respiratory tract infection, nasal and/or sinus disease,
• Be on medication, with the exception of oral contraceptives
• Pregnant or breast-feeding woman (check with urine pregnancy tests);
• Contraindications to TMS or MRI (implanted medical devices or metallic foreign body in the head);
• Psychiatric disorders
• Use of psychotropic drugs
• Have participated in a study involving the injection of a radiotracer during the year

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Presence of early trauma; In the "presence of early trauma" arm, 15 participants are recruited based on a high Childhood Trauma Questionnaire total score.	Other: High score at Childhood Trauma Questionnaire.; In the "presence of early trauma" arm, 15 participants are recruited based on a high Childhood Trauma Questionnaire total score.
Other: Absence of early trauma; In the "absence of early trauma" arm, 15 participants are recruited based on a low Childhood Trauma Questionnaire total score.	Other: Low score at Childhood Trauma Questionnaire.; In the "absence of early trauma" arm, 15 participants are recruited based on a low Childhood Trauma Questionnaire total score.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dopamine transmission measured with positron emission tomography	Subcortical dopaminergic transmission will be analyzed, using [11C]raclopride PET activity (D2 receptor antagonist)	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Odor hedonic appreciation.	The pleasantness of the odors presented will be assessed on a scale of 1 to 9.	24 months
Functional brain connectivity.	Resting-state functional connectivity assessed with fMRI.	24 months
Effective brain connectivity	Effective brain connectivity will be assessed using a dual-coil TMS protocol that stimulates the motor cortex and dorsolateral prefrontal cortex during odor presentation. Measurement of the amplitude of the motor response reflects the connectivity between these two regions of interest.	24 months

Collaborators and Investigators

• Sponsor: Hôpital le Vinatier
• Investigators: Study Director: JEROME BRUNELIN, PSYR2

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: February 13, 2024
• First Submitted That Met QC Criteria: February 26, 2024
• First Posted (Actual): February 28, 2024

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Trauma and Stressor Related Disorders; Stress Disorders, Traumatic; Wounds and Injuries; Psychological Trauma
• Other Study ID Numbers: 2022-A02736-37

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No