UNDERSTANDING SLEEP

Sleep is divided into a variety of stages. The major division is that between rapid eye movement (REM) sleep and non-REM sleep. Most, but not all, dreams occur during REM. Additionally, during REM, the body is essentially paralyzed. The paralysis is useful in that it prevents people from acting out their dreams. The brain waves in REM are very rapid and desynchronized. NonREM sleep is divided into three stages. Here, we look first at the third stage. It is the deepest sleep and is known as slowwave sleep (SWS), because the brain waves recorded during this type of sleep by electroencephalogram (EEG) are slow. They are also synchronized. It is thought that slow-wave sleep is the major restorative sleep. The amount of this sleep will determine whether you"

"feel you have obtained a good night's rest when you awake in the morning. Stage 1 and 2 sleep is intermediate between REM and slow-wave sleep with respect to rate and degree of synchronization. While the majority of dreaming occurs during REM, it also occurs during other stages, particularly if the sleep is light and the sleeper can be easily awakened.

UNDERSTANDING PTSD AND SLEEP

It is thought that PTSD is associated with a failure to process and neutralize frightening memories. This failure allows frightening memories to push in during waking and sleeping hours. Because processing normally occurs during sleep, particularly REM sleep, and nightmares disrupt sleep, a vicious cycle begins, in which the processing of frightening memories is compromised. This has led to the use of a variety of psychotherapies to enhance processing and neutralization of frightening memories to decrease their ability to disturb sleep and to enhance sleepmediated processing of disturbing thoughts. Alternatively, there are medications that decrease disturbing dreams. The effect of medications on processing frightening memories is unclear, but the two approaches may be complementary since medications may be helpful in breaking the vicious circle noted above."

ALL SYSTEMS NOT GO: SOME OF THE DIFFICULTIES

Stress in general, and PTSD, in particular, is thought to be associated with activation of the noradrenergic system (NAS). The noradrenergic system consists of the neurotransmitter norepinephrine and its receptors, which are found in the central nervous system and throughout the body—on nerves, blood vessels, and organs, including the heart. There are many types of noradrenergic receptors, alpha (alpha1 and alpha 2) and beta. The noradrenergic system is thought to play a role in the transition from acute stress disorders to chronic stress disorders and to be central to the symptoms in established cases of PTSD. Alpha receptors are believed to have the predominant role in these symptoms, including sleep disruption and intrusions of unwanted and frightening thoughts while patients are awake or asleep. The understanding of the role that the noradrenergic system plays has led to the use of medications that block the noradrenergic system as a way of treating sleep disorders and nightmares.

Evidence for the role that the noradrenergic system plays includes the following: Many of the areas of the brain thought to be associated with PTSD symptoms are heavily stimulated by noradrenergic (NA) neurons and express a high density of nordrenergic receptors. They are very responsive to activation of the system. Furthermore, concentrations of noradrenergic neurons in the cerebrospinal fluid (CSF) are highly correlated with the severity of symptoms of PTSD, and excretion by noradrenergic neurons of Norepinephrine and its metabolites are increased in the urine of patients with PTSD.

Laboratory studies show that increased noradrenergic activity has a variety of bad effects on a person's REM sleep. These include the diminishing of REM-associated paralysis, leading to increased movements during REM, which may lead to waking up. In addition, shifts from REM to other stages are increased. Thus, noradrenergic system activation is associated with REM fragmentation (waking up throughout the night, reducing the total amount of time spent in the deeper levels of sleep). Poorquality REM sleep, in addition to leading to awakenings, also prevents a person from processing stressful memories. This leads to waking up more often and decreased processing. In addition, NA stimulation is associated with the lightening of types of sleep other than REM and increased levels of corticotrophin releasing factor (CRF). Corticotrophin releasing factor is a hormone produced by the hypothalamus that leads to anxiety, including an increase in a person's primitive internal alarm system. Furthermore, it leads to release of Norepinephrine by noradrenergic neurons, which in turn leads to further release of corticotrophin releasing factor, again, increasing a person's anxiety level.

THE ROLE OF MEDICATIONS

All this suggests that medications that interfere with the noradrenergic system might be useful in PTSD. Clonidine is one such medication. It is an activator (agonist) of the type 2 alpha receptor, a receptor that decreases noradrenergic neuron release of Norepinephrine. Thus, clonidine causes the noradrenergic system to regulate down. Its major use in medicine is to treat hypertension – hence, hypotension is one of its side effects. Its peak effect occurs one to three hours after it is taken by mouth, and a usual dosage is .2 to.4 mg. Aside from hypotension, bad side effects are dry mouth, drowsiness, and constipation. The beneficial effects may wear off in time, requiring an increase in the dosage. There have been a number of reports of its successful use for those with PTSD, particularly in children.

Recently, most studies of medications to regulate the noradrenergic system have focused on prazosin, which blocks the alpha1 receptor. It is used for hypertension and urinary difficulties that are secondary to a non-life threatening enlargement of the prostate. Multiple studies of this medication have shown its use for the treatment of PTSD, particularly for the treatment of nightmares and sleep disturbances. Interestingly enough, it specifically decreases the abnormal nightmares that occur with PTSD. Normal nightmares and normal dreams have