Sleep and Circadian Rhythms

•Sleep disorders and insomnia are very common and can lead to other medical problems

•Insufficient sleep syndrome-common in population - work demands, etc.

•Some psychopathologies are associated with sleep disorders

•Psychopathologies may also reflect circadian disorders

Why should patients ask their physician about sleep disturbances?

Who else are they going to ask?

Who else would know where to refer them?

Sleep behavior should be queried in a routine examination.

Circadian Rhythms, Entrainment and the SCNDark Light

M.U. Gillette and S.A. Tischkau. 1998. Recent Progress in Hormone Research. 5: 33-59

Circadian Rhythms

Some concepts:

“Circa” = about; “Dia” = day; about the day

In a steel mill, the blast furnaces are readied before the workers arrive

•Intrinsic rhythms

•Entrainment

•Free run

Circadian rhythms

Circadian rhythms ("circa," about; "dia," day) are those that occur on a 24 hour daily cycle.

A variety of studies in animals supported by human clinical studies indicate that the suprachiasmatic nucleus, in the hypothalamic region of the brain is the highest level pacemaker, with an intrinsic rhythm of about 24 hours' duration. This intrinsic rhythm in turn becomes entrained by environmental cues, typically the light-dark cycle.

The psychiatric disorder that appears to be most closely related to circadian rhythmicity is seasonal affective disorder (listed as bipolar 1 disorder, bipolar II disorder or major depressive disorder, recurrent, “with seasonal pattern”), a cyclothymic (depressive) disorder that tends to occur in the fall or winter as daylength shortens.

Seasonal affective disorder often goes into full remission (or a change from depression to mania or hypomania) as daylength increases in the spring. This is often diagnosed when there are regular seasonally-occuring depressive episodes (at least twice) and no other periods of depression. This disorder often responds to lithium treatment or lithium combined with other antidepressants.

However, it has also been shown that SAD can be treated by exposure to bright lights that contain the ultraviolet spectrum. As yet, the effects of light therapy on depressed patients with other etiologies have not been thoroughly evaluated, so specificity to this disorder is uncertain.

Things about circadian rhythms you need not know for the exam

•Jet lag arises from a dissociation of secondary endogenous rhythms. Adaptation is re-synchronization•Seasonal affective disorder is a mood (depressive) disorder that involves exposure to ultraviolet light•Mood disorder responsive to Lithium treatment is associated with an overly long intrinsic rhythm

Circadian Rhythm Sleep Disorder

A persistent or recurrent pattern of sleep disruption leading to excessive sleepiness or insomnia that is due to a mismatch between the sleep-wake schedule required by a person's environment and his or her circadian sleep-wake pattern.

The sleep disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.

The disturbance does not occur exclusively during the course of another Sleep Disorder or other mental disorder.

The disturbance is not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition.

EEG slide

Physiology and Behavior of Non-REM and REM Sleep

Autonomic Regulation:Cerebral Blood Flow Low HighBrain Temperature Reduced IncreasedBody Temperature Regulation Normal ImpairedRespiration Slow VariableHeart Rate Slow Variable

Skeletal Musculature:Muscle Tone Reduced GoneKnee Jerk Reflex Normal InhibitedBody Twitches Infrequent FrequentEye Movements Infrequent, slow, Rapid, conjugate

nonconjugate

Cognition: Wandering, vague Vivid dreams

Neural Activity:Cerebral Cortex Unit Reduced activity, Increased activity, phasic tonicEEG Slow large waves, High frequency, waking-like

delta

REM Sleep as a Percent of Total Sleep by Age

SLEEP DISORDERS

Dyssomnias: True disorders of sleeping

* Intrinsic (e.g., intrinsic insomnias, hypersomnias, narcolepsy, sleep apneas, limb movement disorder)

* Extrinsic (e.g., altitude insomnia, stimulant-dependent sleep disorder, alcohol-dependent sleep disorder)

* Circadian rhythm (e.g., time zone change (jet-lag), shift-work, delayed or advanced sleep phase syndrome)

Parasomnias: Abnormal behaviors that interrupt sleep

* Arousal disorders (e.g., sleep walking, sleep terrors [non-REM, vs. nightmares])

* Sleep-wake transition disorders (e.g., sleep talking, nocturnal leg cramps)

* Parasomnias of REM sleep (e.g., nightmares)

* Other parasomnias (e.g., sleep enuresis, SIDS)

Extended sleep disorders overhead

SLEEP DISORDERS (cont'd.)

Medical-Psychiatric Sleep Disorders:

* Associated with mental disorders (e.g., mood disorders, anxiety, schizophrenia)

* Associated with neurological disorders (e.g., Dementia, Parkonsonism, sleep-related epilepsy)

* Associated with other medical disorders (e.g., sleeping sickness, nocturnal cardiac ischemia)

CHRONIC INSOMNIA

* 20% to 30% of the adult population complains of trouble sleeping.* Most common: persistent difficulty in getting to sleep (>45 min., > 3 X / week, > 3 weeks)

Most Common Causes:

* Emotional style (anxiety, depression, hyperaroused-restless)

* Conditioned poor sleep: loss of "confidence" in the ability to sleep (often following events that disrupt sleep for several nights)

* Drugs: Use or withdrawal from cigarettes, alcohol (induces sleep but with "rebound" @ 3-4 hrs.), diet pills, prescription drugs (benzodiazepines can reduce delta sleep; cyclic antidepressents reduce REM sleep); consumption of coffee

* Medical-psychiatric disorders (Major Mood/Affective Disorders)

* Intrinsic sleep disorder (periodic limb movement disorder, sleep apnea)

If an intrinsic disorder is suspected, a polysomnogram (PSG) or clinical sleep recording from a sleep lab is warranted.* EEG, eye movements* Chin, limb EMG (tone; sleep movement disorders)* Respiration (sleep apneas)

TREATMENTS FOR SLEEP DISORDERS

* Psychotherapy (control of negative thoughts, etc.)

* Pharmacotherapy (short-term, not chronic!) (benzodiazepines: Halcion, Restoril)

* Behavioral (e.g., progressive relaxation, biofeedback, thought stopping)

* Sleep hygiene (regular schedule, minimize light and noise, eliminate non-prescription drugs, exercise, etc.)

Disorders of Excessive Daytime Somnolence

(Falling asleep at a desk or IN CLASS!)

Insufficient Sleep Syndrome: pressures of work, being on call, late partying. Treatment: induce common sense; revamp the practice of medicine.

Sleep Apneas: Daytime sleepiness due to sleep disturbance. Mostly middle-aged, older males with obstructive sleep apnea, a breathing disorder. May be associated with obesity, excess alcohol or drug use. Other apneas of central origin also are seen, but rare. Obstructive sleep apnea may be treated by sleep position training, weight loss, alcohol reduction, mechanical devices to improve breathing, or surgery (e.g., tonsillectomy).

Narcolepsy: Pathological daytime sleepiness. Diagnosed by absence of apneas, rapid onset of REM. Multiple sleep latency test (5 daytime naps at 2 hr intervals following the nighttime PSG) to see if REM onset is rapid during the day. Can be treated with stimulant drugs.

Parasomnias

Disorders such as sleepwalking and sleep terrors tend to occur in children and adolescents and to disappear in adulthood. Sleepwalking may occur/recur in adults under stress.

Sleep Deprivation Effects

Mild: increased irritability, difficulty in concentrating, disorientation (particularly in the morning), impaired sensory-motor coordination and performance.

Severe: Hallucinations, "bizarre" behaviors can result

Recovery from deprivation: Compensatory increases in REM and delta sleep occur during subsequent sleep cycles; "intensity" of rapid eye movements and other sleep characteristics may increase.

Intense exercise, e.g. marathons, increase sleep time, particularly deep non-REM delta sleep.

Learning and Sleep

Learning during sleep: it happens, especially in the lighter stages of sleep, but it is not a particularly efficient way to learn.

There is evidence for a relationship between REM sleep and memory formation:* REM sleep increases following learning and in rats in enriched environments* Material learned before a night's sleep is better remembered in the morning than

a list learned prior to 8 hours waking before recall testing.* REM deprivation in advance impairs learning* REM deprivation after learning: data equivocal