Sleep and Cardiovascular Health in Adolescence

Insomnia is highly prevalent in adolescence, particularly in post-pubertal girls and tends to
persist over time. Insomnia is considered a hyperarousal disorder, in which abnormally
elevated levels of cognitive and physiological activation, particularly evident at bed-time,
prevent individuals from falling asleep and having a restorative night's sleep. Hyperarousal
is a major pathophysiological mechanism linking insomnia with poor mental and physical
health, including cardiovascular (CV) disease. The investigators and others have shown
evidence of autonomic nervous system (ANS) dysfunction such as hyperactivation of the
sympathetic branch of the ANS - a major etiological factor in CV disease - in young and
midlife adults, both before and during sleep. It is unknown if ANS hyperarousal is evident in
adolescents with insomnia.

The biological basis for an emerging sex difference in insomnia prevalence in adolescence is
unknown. The investigators' pilot data reveal intriguing evidence of sex-differences in basic
and stress-dependent ANS modulation during sleep in adolescents with girls showing a greater
ANS response to stress. These data suggest the existence of a predisposing and
stress-dependent ANS vulnerability in female adolescents, a potential pathway to develop
insomnia. This study takes a novel approach to investigating the manifestation of
physiological ANS and CV hyperarousal in adolescents with insomnia by experimentally
manipulating the pre-sleep arousal state via stress-induced ANS up-regulation and
relaxation-driven ANS down-regulation. In addition, the study focuses on sex differences in
ANS and CV responses to pre-sleep ANS manipulation, potentially addressing the question of
why female sex is a major risk factor for insomnia.

The investigators aim to test 110 male and female high-school students (16-20y) with and
without DSM-5 Insomnia Disorder, during a regular in-lab polysomnographic night (baseline)
and under experimental pre-sleep stress (psychosocial stressor) and pre-sleep relaxation
(Virtual reality ANS bio-feedback) intervention nights, using state-of-the-art, noninvasive,
beat-to-beat ANS and CV measures, including blood pressure, to assess nocturnal ANS and CV
function in adolescents with insomnia (Aim 1); the impact of pre-sleep ANS arousal levels on
nocturnal ANS and CV function, and sleep in adolescents with and without insomnia,
considering possible sex differences (Aim 2), and the extent to which nocturnal ANS and CV
function mediate the effect of pre-sleep arousal levels on objective and perceived sleep
quality (Aim 3).

This study has the potential to elucidate pathophysiological ANS hyperarousal underlying
Insomnia Disorder in adolescence, including potential reasons for the vulnerability to
insomnia in girls, leading to better recognition and potentially new treatment strategies of
this disorder targeted at the state of ANS hyperarousal in the pre-sleep period.

Inclusion Criteria:

- Must be post-pubertal

- BMI <30 kg/m-2 to reduce the likelihood of obesity-related sleep-disordered breathing

Exclusion Criteria:

- Current use of drugs known to affect sleep and CV systems (e.g., Antidepressants,
stimulants, beta-blockers)

- Serious history of, or current medical conditions that could affect brain function, or
study participation, including Diabetes, cancer, neurological diseases (e.g., Seizure
disorders) recurrent migraine, cardiovascular diseases (e.g., Hypertension) and
traumatic brain injury with loss of consciousness >30 minutes

- Current DSM-5 diagnosis of Neurodevelopmental Disorders (e.g.,
Attention-Deficit/Hyperactivity Disorder)

- Current DSM-5 diagnosis of Schizophrenia Spectrum and Other Psychotic Disorders,
Bipolar and Related Disorders

- Current DSM-5 diagnosis of Depressive and Anxiety Disorders (e.g., Major Depressive
Disorder)

- Current DSM-5 diagnosis of Post-Traumatic Stress Disorder

- Current DSM-5 diagnosis of Substance-Related and Addictive Disorders (e.g., Alcohol
Use Disorder)

- History of and persistence in severe learning disorder, pervasive developmental
disorder, or other condition requiring repeated or persistent specialized education
(e.g., Estimated intellectual quotient (IQ) >2 standard deviations below mean)

- Current psychiatric disorders in both control and insomnia groups is exclusionary

- Past history of psychiatric disorders in controls is exclusionary (past history of
psychiatric disorders in the insomnia group is not exclusionary)

- Shift work in the previous year and no time-zone travel in the past month

- Evidence of other DSM-5 Sleep-Wake Disorders (e.g., Narcolepsy), Breathing-Related
Sleep Disorders (e.g., Obstructive Sleep Apnea Hypopnea, Circadian Rhythm Sleep-Wake
Disorders and particularly Delayed Sleep Phase Type), and Parasomnias (e.g., Non-Rapid
Eye Movement Sleep Arousal Disorders, Rapid Eye Movement Sleep Behavior Disorder and
Restless Legs Syndrome)

- Current pregnancy