Characteristics of Sleep Patterns in Young Adults With and Without Insomnia

The overall aim of this research study is to compare the symptoms, experiences and
laboratory sleep characteristics of young adults with and without insomnia. Insomnia is a
pattern of difficulty falling asleep, staying asleep or feeling poorly rested despite an
adequate amount of time for sleep, which occurs nearly every night for one month or longer.
For those with insomnia, we will look at the effects of an intervention with one of two
medications (escitalopram or zolpidem) or an inactive pill (placebo). This intervention will
be followed by re-evaluation of symptoms, experiences and laboratory sleep characteristics.
The three hypotheses being investigated are: compared to control subjects, those with
insomnia will demonstrate affective disturbance and heightened arousal; the different
medications will have different degrees of effect on the two dimensions being measured
(affective disturbance and heightened arousal); and PET scans will reveal different patterns
of activity in the brains of groups of people with insomnia.

We will specifically focus on the syndrome of Primary Insomnia (PI), defined by DSM-IV as
insomnia that lasts for at least one month and causes significant impairment or distress. PI
excludes insomnia that occurs exclusively during the course of another sleep, mental,
substance-induced, or medical disorder. Insomnia is a significant public health problem
because of its prevalence, morbidity, and the risk it poses for the development of
subsequent mental disorders, particularly depressive and anxiety disorders. Understanding
the psychobiology of primary insomnia is a critical step toward addressing questions
regarding its relationships with mood and anxiety disorders.

Our model of insomnia builds on two major concepts running through previous insomnia
research, affective disturbance and heightened arousal, as driving factors for the
sleep-wake disturbances that define PI. Implicit in this model is that individuals with PI
have different degrees of each dysfunction, which accounts for their heterogeneity of
clinical symptoms. Contemporary theories of affect structure suggest that these two
dimensions may be orthogonal in pure form, but are nevertheless related in clinical
conditions characterized by mixed anxiety-depression, such as PI. Measures of affective
disturbance and arousal in this study will include questionnaires, diary-based assessments,
and physiological measures.

Pharmacological treatment probes may help to further distinguish the roles of affective
disturbance and heightened arousal in insomnia. We will use a benzodiazepine receptor
agonist (BzRA), zolpidem, and an antidepressant, escitalopram. BzRA potentiate the effects
of GABA (1), but have minimal direct activity at any other receptor types. They are
efficacious treatments for insomnia (2-4), but have little effect on mood. We chose zolpidem
because it is relatively specific for hypnotic versus anxiolytic or other actions (5),
because it is the most widely-prescribed BzRA hypnotic, and because it is well-tolerated
(6). Clinically-effective doses of even "nonsedating" antidepressants can also improve
symptoms in PI (7), suggesting that direct sedation is not their only mechanism for
improving insomnia. We chose escitalopram because it is neither strongly alerting nor
sedating in clinical and polysomnographic studies. This "sleep-neutral" profile will allow
us to use it for its effects on affective disturbance, rather than its nonspecific sedating
properties. Escitalopram's specific effect on serotonin reuptake blockade and its lack of
affinity for Bz receptors distinguish it from zolpidem as a pharmacologic probe.

Functional neuroimaging studies in wakefulness and sleep may also help to identify the
substrate of affective disturbance and heightened arousal in insomnia. Affective disturbance
in the form of MDD is associated with alterations in both regional deactivation patterns
during NREM sleep, and regional activation patterns during REM sleep. These observations
suggest that a sleep-wake functional neuroimaging paradigm in insomnia patients, in
conjunction with behavioral measures, may help to identify which brain systems mediate
heightened arousal and affective disturbance, and how these systems interact.

Inclusion Criteria:

- Physically healthy

- Meets DSM-IV criteria for primary insomnia

- For subjects interested in PET study only: right-handedness

Exclusion Criteria:

- Currently taking antidepressants, antianxiety medications or medications for sleep
disorders

- Currently experiencing symptoms of psychiatric disorders such as major depressive
disorder, bipolar disorder, generalized anxiety disorder

- Significant or unstable acute or chronic medical conditions, such as seizure
disorder, tumor, liver disease, active peptic ulcer disease, arthritis, irritable
bowel disease

- Meets DSM-IV criteria for sleep apnea or periodic limb movement disorder