There are three peripheral SNS systems which are preferential to different catecholamine (i.e., EPI, NE, DOPA) release(s). These three systems include: 1) sympatho-adrenomedullary system; 2) sympatho-neural system; and 3) DOPA-dopamine autocrine/paracrine system. As such, we will use six sympathetic stressors to observe the catecholamine responses across these three peripheral systems in individuals with DS compared to age- and sex-matched individuals without DS. The six optional SNS stressors are 1) Cold Stress, 2) Fear via Virtual Reality, 3) Pain via Capsaicin Cream, 4) 12-Hour Fast, 5) Caffeine, and 6) Maximal Dynamic Exercise. Each of these stressors are optional.

Who can Participate

Individuals with and without DS Population: Individuals with and without DS Inclusion Criteria: - 18-50 yrs old and apparently healthy individuals - Ability to understand the study and give assent to participate - Has a study partner who can attend all visits for the individuals with DS, and answer questionnaires, provide consent when necessary - Corrected or non-existent congenital heart disease - Euthyroid or on stable thyroid medication dose for at least 6 months - Free from cardiovascular, pulmonary, inflammatory, or metabolic disease in the past 6 months that would prevent participation in study procedures - BMI <45kg/m2 - Ability to tolerate repeated blood draws / catheter placement Exclusion Criteria: - Hypertension (resting systolic blood pressure [SBP] >140 and/or diastolic blood pressure [DBP] >90 mmHg) this includes those on medications to treat hypertension - Hypotension (resting BP of <90/60 mmHg) - Cancer in the last six months - Any heart-rate-altering medications or any other medication that may modify metabolic responses - Self-reported diabetes or use of glucose-lowering medication - Tobacco products, including vaping, or marijuana use - Currently pregnant - Post-menopausal women Specific Exclusion Criteria for Certain Stressors: - Orthopedic limitations that would prohibit exercise or movement for exercise - Fracture of limb to be immersed for cold pressor test (CPT) - Open cut or sore on hand to be immersed for CPT - Raynauds syndrome for CPT - Chronic caffeine drinkers for caffeine stressor (consumption of caffeine in the last 7 days) Participants with and without DS will be grouped in a 1:1 fashion based on age and sex where possible, to minimize confounding effects and better isolate phenotype-specific differences associated with Trisomy 21.

Study ID