Adolescence
Conditions
Keywords
anxiety, exercise, fear
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.
Interventions
BEHAVIORALModerate Intensity Exercise
Participants randomized to the active (moderate intensity) exercise condition will complete a 3-minute warm-up at low speed on a treadmill. Speed and incline will be increased in 3-minute increments until moderate-intensity exercise, defined as participants staying within a zone of 60-80% AAMHR with the target being to attain and maintain 70-75% AAMHR while briskly walking and/or jogging depending on current fitness status, is reached for a total of 30 min.
Sponsors
National Institute of Mental Health (NIMH)
Wayne State University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Years to 17 Years
Healthy volunteers
Yes
Inclusion criteria
1. Provision of signed and dated informed consent form 2. Stated willingness to comply with all study procedures and available for the duration of the study 3. 14-17 years of age upon enrollment 4. Right-handed 5. In good general health as evidenced by medical history 6. Adolescent and parent/guardian are English-speaking, as study assessments are in English 7. Availability of a parent or legal guardian who is willing to provide consent and attend all study visits
Exclusion criteria
1. Traumatic brain injury with ongoing symptoms 2. Sensory (e.g., hearing) or physical (e.g., motor, balance) impairment or significant developmental delay 3. MRI participants: MRI contraindication (e.g., braces, implants, claustrophobia) 4. Any condition that would contraindicate blood draws (e.g., hemophilia, sickle cell) 5. Past or current diagnosis or presence of likely neurological disorder (e.g., epilepsy), psychotic disorder (e.g., schizophrenia, schizoaffective disorder), or bipolar disorder 6. Severe/unstable medical condition (e.g., diabetes, rheumatoid arthritis) 7. 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 8. Currently pregnant, lactating, or positive pregnancy test at screening visit 9. Current homicidal thoughts or suicide attempt in the past year 10. Current suicidal thoughts requiring immediate intervention 11. Concurrent use (past 6 weeks) of oral contraceptives 12. Diagnosed or probable substance use disorder (past 1-month) 13. Positive drug test at baseline visit (e.g., THC, cocaine) 14. Moderate/severe drug or alcohol use in the past 8 weeks 15. Current or recent (past 1-month) COVID-19 diagnosis or febrile illness 16. Treatment with investigational drug or intervention (past 1-month) 17. Current smoker, vaper, or tobacco or nicotine use (past 1-month) 18. Ongoing exposure to abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Skin Conductance Responding (SCR) | 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 | Throughout study completion (3 days) | US Expectancy Ratings will be measured during fear learning, extinction, and recall tasks |
| Fear extinction neural circuitry: Functional activation and coupling | 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). |
| Endocannabinoid (eCB) Concentrations | 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
| Measure | Time frame | Description |
|---|---|---|
| Approach/Avoidance Behavior | Throughout study completion (3 days) | The investigators will quantify forward-to-backward response pad distance in virtual meters from the conditioned stimulus. |
| Amygdala response during extinction recall | 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. A secondary region of interest is amygdala response during recall (CS+E\>CS+U). |
| Fear Ratings | Throughout study completion (3 days) | Fear ratings to each CS will be captured at the beginning, middle, and end of each phase, using a response pad and a 1-5 visual analog scale (1 = not scary at all, 5 = very scary). |
Countries
United States
Outcome results
None listed