Exercise Facilitation of Adolescent Fear Extinction, Frontolimbic Circuitry, and Endocannabinoids
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Wayne State University
- Enrollment
- 174
- Locations
- 2
- Primary Endpoint
- Fear extinction neural circuitry: Functional activation and coupling
Study Overview
Brief Summary
Anxiety disorders commonly begin during adolescence, and are characterized by deficits in the ability to inhibit or extinguish pathological fear. Recent research has provided new understanding of how fear is learned and can be regulated in the adolescent brain, and how the endocannabinoid system shapes these processes; however, these advances have not yet translated into improved therapeutic outcomes for adolescents with anxiety. This study will test whether a behavioral intervention, acute exercise, can help to improve fear regulation by enhancing brain activity and endocannabinoid signaling. This line of research may ultimately lead to more effect treatments for adolescent anxiety, and to new preventive strategies for at-risk youth.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 14 Years to 17 Years (Child)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Provision of signed and dated informed consent form
- •Stated willingness to comply with all study procedures and available for the duration of the study
- •14-17 years of age upon enrollment
- •Right-handed
- •In good general health as evidenced by medical history
- •Adolescent and parent/guardian are English-speaking, as study assessments are in English
- •Availability of a parent or legal guardian who is willing to provide consent and attend all study visits
Exclusion Criteria
- •Traumatic brain injury with ongoing symptoms
- •Sensory (e.g., hearing) or physical (e.g., motor, balance) impairment or significant developmental delay
- •MRI participants: MRI contraindication (e.g., braces, implants, claustrophobia)
- •Any condition that would contraindicate blood draws (e.g., hemophilia, sickle cell)
- •Past or current diagnosis or presence of likely neurological disorder (e.g., epilepsy), psychotic disorder (e.g., schizophrenia, schizoaffective disorder), or bipolar disorder
- •Severe/unstable medical condition (e.g., diabetes, rheumatoid arthritis)
- •Current (past 1-month) use of cannabis or cannabinoid products including CBD unless willing to stop for at least 4 weeks prior to entering the study
- •Currently pregnant, lactating, or positive pregnancy test at screening visit
- •Current homicidal thoughts or suicide attempt in the past year
- •Current suicidal thoughts requiring immediate intervention
- •Concurrent use (past 6 weeks) of oral contraceptives
- •Diagnosed or probable substance use disorder (past 1-month)
- •Positive drug test at baseline visit (e.g., THC, cocaine)
- •Moderate/severe drug or alcohol use in the past 8 weeks
- •Current or recent (past 1-month) COVID-19 diagnosis or febrile illness
- •Treatment with investigational drug or intervention (past 1-month)
- •Current smoker, vaper, or tobacco or nicotine use (past 1-month)
- •Ongoing exposure to abuse
Outcomes
Primary Outcomes
Fear extinction neural circuitry: Functional activation and coupling
Time Frame: Neuroimaging will occur during the fear extinction recall phase on Day 3
MRI eligible only: fMRI blood-oxygen-level-dependent (BOLD) response will be measured across the entire brain during a test of extinction recall. The investigators will focus on response in the hippocampus and ventromedial prefrontal cortex activation and coupling (gPPI) during recall (CS+E\>CS+U).
Skin Conductance Responding (SCR)
Time Frame: Throughout study completion (3 days)
To compare the effects of acute moderate-intensity exercise (vs. sedentary control) on extinction recall, the investigators will place three electrodes on participant's left hand to acquire SCR data using a BIOPAC MP160 Data Acquisition System (BIOPAC Systems, Inc.).
Unconditioned Stimulus (US) Expectancy Ratings
Time Frame: Throughout study completion (3 days)
US Expectancy Ratings will be measured during fear learning, extinction, and recall tasks
Endocannabinoid (eCB) Concentrations
Time Frame: eCB concentrations will be measured in plasma and saliva immediately before and after the exercise or control condition on Day 2
Plasma and saliva samples will be collected immediately before and after exercise or sedentary control condition. Samples will be analyzed using liquid chromatography-mass spectrometry to quantify concentrations of eCBs.
Secondary Outcomes
- Fear Ratings(Throughout study completion (3 days))
- Approach/Avoidance Behavior(Throughout study completion (3 days))
- Amygdala response during extinction recall(Neuroimaging will occur during the fear extinction recall phase on Day 3)
Investigators
Hilary Marusak
Assistant Professor
Wayne State University