Interaction Between Early Trauma and Odor-induced Dopamine Release

Trauma, Psychological Clinical Trial

— T-ODOR  

Official title:

Consequence of Early Trauma on Odor Hedonics Appreciation and DOpamine Release

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06284382
• Other study ID #: 2022-A02736-37
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 1, 2024
• Est. completion date: June 1, 2027

Study information

• Verified date: February 2024
• Source: Hôpital le Vinatier
• Contact: FILIPE GALVAO
• Phone: 0033437915565
• Email: filipe.galvao[@]ch-le-vinatier.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: June 1, 2027
• Est. primary completion date: June 1, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 30 Years

Eligibility

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

Related Conditions & MeSH terms

• Psychological Trauma
• Trauma, Psychological
• Wounds and Injuries

Intervention

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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hôpital le Vinatier

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dopamine transmission measured with positron emission tomography	Subcortical dopaminergic transmission will be analyzed, using [11C]raclopride PET activity (D2 receptor antagonist)	24 months
Secondary	Odor hedonic appreciation.	The pleasantness of the odors presented will be assessed on a scale of 1 to 9.	24 months
Secondary	Functional brain connectivity.	Resting-state functional connectivity assessed with fMRI.	24 months
Secondary	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