Clinical trial NCT05825677: Investigating Stress-Induced Dopamine Release: a fMRI-PET Study
Official title: Investigating Stress-Induced Dopamine Release: a fMRI-PET Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Stress Response
Lead sponsor: Hôpital le Vinatier
Sponsor class: OTHER
First posted: 2023-04-24
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: In a randomized controlled double-blind study, 30 healthy subjects, will be randomly assigned to 2 groups. A group of 15 participants will receive 30 minutes of active tDCS (1mA, 30 minutes with the anode at the left DLPFC and the cathode at the right DLPFC); a group of 15 participants will receive 30 minutes of placebo stimulation. All participant will be in a PET-MRI scanner for 110min, during which they will undergo the stimulation (either active or sham). During this stimulation session, all participants will undergo a standardized stress test combining psychosocial stress and physical stress.
Primary purpose: BASIC_SCIENCE

Brief summary: The stress response is mediated by the activation of the hypothalamo-pituitary-adrenal axis and the sympathetic nervous system, leading to glucocorticoid and catecholamines release respectively. This stress response is regulated by feedback loops, involving cortical and subcortical structures.

Non-invasive brain stimulation applied over the dorsolateral prefrontal cortex modulates the subcortical dopaminergic transmission at rest and can reduce the hormonal and cognitive alterations induced by stress. This study aims to investigate the Non-invasive brain stimulation -induced modulation of dopamine transmission in an acute stress situation.

Detailed description: Objective: to investigate the influence of Dorsolateral Prefrontal Cortex stimulation during acute stress on the subcortical dopamine transmission in healthy subjects.

Method: 30 healthy subjects will be enrolled and randomized into 2 parallel groups. 15 participants will receive active Transcranial direct current stimulation , the other 15 participants will receive sham Transcranial direct current stimulation.

Transcranial direct current stimulation procedure: active Transcranial direct current stimulation corresponds to 30min of stimulation at 1mA intensity . The sham stimulation corresponds to 30s of real stimulation.

Stress paradigm: In order to induce moderate stress in humans in laboratory condition, the investigators will use the Maastricht Acute Stress test . This test is a combination between physical, hand immersion in cold water and cognitive calculation stress. The test will start 5 minutes after the beginning of stimulation session.

Stress measures: the stress response will be evaluated at the following levels:

* Neurochemical level: dopamine transmission measured with positron emission tomography
* Functional brain connectivity: resting-state networks measured with functional magnetic resonance imaging
* Hormonal level: adrenocorticotropic hormone and cortisol levels measured with blood samples
* Cognitive level: decision-making and memory assessed with delay-discounting task and reality-monitoring task, respectively
* Molecular level: expression of genes involved in the glucocorticoid receptor signaling pathway measured through blood samples Exploratory measure: Brain-Derived Neurotrophic Factor and cytoplasmic catechol-O-methyltransferase polymorphisms of participants involved in differential Transcranial direct current stimulation response will be assessed.

Eligibility criteria: Inclusion Criteria:

* - Men and women aged between 18- and 30-year-old
* Non-smoker
* Non-psychotropic user

Exclusion Criteria:

* - Have a psychiatric or somatic disorder
* Have a first-degree family history of a psychiatric disorder
* Pregnant or nursing women
* Be on medication, with the exception of oral contraceptives
* Contraindications to tDCS or MRI examination
* Participants with pacemaker or cardiac or cerebral implant

Primary outcomes:
measure: Dopamine transmission measured with positron emission tomography
timeFrame: One year
Secondary outcomes:
measure: Functional brain connectivity
timeFrame: One year
measure: Hormonal stress reactivity
timeFrame: One year
measure: Cognitive stress reactivity
timeFrame: One year
measure: Expression of genes involved in the glucocorticoid receptor signaling pathway measured through blood samples
timeFrame: One year
measure: Assessment of brain-derived neurotrophic factor before and after transcranial direct current stimulation.
timeFrame: One year
measure: Hormonal stress reactivity
timeFrame: One year
measure: Assessment of Cytoplasmic catechol-O-methyltransferase polymorphisms before and after transcranial direct current stimulation.
timeFrame: One year
Other outcomes:
Locations:
city: Lyon
country: France
facility: Ch Le Vinatier
state: Rhone Alpes
Study officials:
affiliation: Vinatier Hospital PsyR2 Team
name: Jérôme BRUNELIN, PhD
role: STUDY_DIRECTOR
References: