Bedfellows: Insomnia and Depression

Sleep disturbances and unipolar depression are such intransigent
bedfellows that troubled sleep is considered a hallmark of the mood
disorder. At least 80% of depressed people experience
insomnia—difficulty falling asleep or, most often, staying asleep.
Indeed, early morning awakening is a virtual giveaway of depression.
Another 15% of the depressed sleep excessively.

But it may be that insomnia is more than just a symptom of
depression. It may in fact unleash the mood disorder. If sleep researcher
Michael Perlis, Ph.D., is right, insomnia may be an early harbinger of
depression. His longitudinal studies show that it appears to precede
episodes of depression by about five weeks. And sleep disorder
intensifies over the course of a new depressive episode or relapse, says
Perlis, associate professor of psychiatry and psychology at the
University of Rochester and director of the behavioral sleep medicine
service.

In a complex mix of chemistry and behavior, disordered sleep may
actually bring on depression, setting in motion an array of forces in the
nervous system that result, ultimately, in a frank depressive episode.
Most intriguing, treating the insomnia may forestall a first episode of
depression or recurrent disorder, or at least keep it from becoming
chronic.

It isn't just that depression sufferers wake up early and get less
sleep. The makeup of their sleep is shattered. Normal sleep has a
well-defined architecture. Four or five times a night we cycle through
periods of deepening, relaxing sleep, marked by slow waves if the brain
is monitored electronically. Then we burst into dream sleep, marked by
dramatic brain activity and rapid eye movements.

Depressed people lapse quickly into REM sleep, as if they were in a
hurry to get to the highly emotionally charged activity. "For some
reason, there is a lot of pressure to get into it," says Perlis. And it's
unusual both in duration and intensity, more dense, intense and
longer-lasting.

The fast track to dreamland is not a good thing. "There's something
about dreaming that is meaningful in depression," Perlis says, intriguing
the Freudian lurking in all of us.

But exactly what it is is not quite clear. "It certainly looks like
REM sleep represents an abnormality in the neurobiologic machinery of
dreaming," says Perlis. "But there is still something wrong with the way
that the depressed dream; the function of dreaming is undermined."

One of the functions of sleep is to facilitate the consolidation of
memory. REM sleep in particular is involved with affective, or emotional,
memory. "There's something wrong with the memories depressed people are
consolidating and the way that the REM system is mood-regulating," says
Perlis.

The intense activation of REM sleep in the depressed may lead to
the overconsolidation of negative memory, rendering the depressed overly
biased to remember bad things. They do not discharge negative feelings
over time.

Disordered REM sleep is a deep marker of depression. REM sleep
remains disordered even in persons whose depression has remitted, and it
is disordered among first-degree relatives of the depressed. It seems to
be related to depression vulnerability. Long-term monitoring of remitted
patients shows that their sleep disturbance becomes progressively worse
before they relapse into the full clinical syndrome of depression. Still,
it is the reduction in slow wave sleep, brought about by the rush to REM
sleep, that correlates most strongly with severity of current depression,
along with the density and duration of REM sleep.

The insomnia that occurs in major depression typically leaves
patients with six or more hours of sleep per night. That, however, is
enough to interfere with one of the primary functions of
sleep—consolidation of learning and memory.

The loss of slow-wave sleep and the rush to REM sleep have a
significant effect on information and memory processing. They enhance it,
and the revved-up ability to recall information appears to get in the way
of perceiving what is actually going on around the time of falling sleep.
As a result, patients with insomnia overestimate the time it takes them
to fall asleep and underestimate the amount of time they actually spend
sleeping.

It's entirely possible that the disturbed sleep that so typifies
depression is the body's own attempt to correct itself. Researchers have
evidence that in a certain proportion of sufferers insomnia has an
antidepressant effect. Evidence has long existed that extended
wakefulness improves the functioning of the serotonin neurotransmitter
system, one of the brain-chemical systems that goes awry in depression.
It may also beef up the release of dopamine, another neurotransmitter
linked to depression.

In fact, sleep deprivation has been used as a depression treatment.
Awakening patients early improves mood in 30% to 60% of cases. The
problem is, the effect is short-lived. Once patients sleep again, they
wake up depressed the next day. A variation of sleep deprivation called
phase advancing, is now used as treatment in some circumstances.

The sleep loss of insomnia may begin, says Perlis, as a
compensatory mechanism, a valiant attempt to enhance serotonin
production. It may also have other antidepressant effects not related to
serotonin. For example, the stress system of depressed people appears to
be in a chronically activated mode, and insomnia may dampen the
hyperarousal of body and brain created by the stress response.

But the insomnia doesn't work well enough to counteract depression.
Its effect on serotonin is not huge. In failing to fully offset the
serotonin deficiency and nervous system fallout from the extended stress
response, insomnia precipitates the other depressive symptoms.

Once a bout of insomnia occurs, most people experience a great deal
of frustration and anxiety about falling asleep and staying asleep. They
take behavioral steps to compensate for the sleep loss, napping during
the day or early evening. They go to bed early the next night. They stay
in bed later the next morning. Or they drink as a way to relax themselves
into sleep.

But these behaviors alter the sleep mechanism and wind up
perpetuating insomnia. And now the insomnia exists as a result of
behavioral contingencies. As a short term insomnia gets transformed into
a persisting state by behaviors intended to counteract it but that
backfire, the sleep loss builds.

Disordered sleep sets off a cascade of symptoms. It leads to
fatigue, irritability, memory and concentration problems, loss of
interest in social and other activities and the inability to draw
pleasure from them. The fatigue strips away libido. Weight loss could
follow extended sleep loss. Insomnia, in short, becomes
depression.

The depression is actually secondary to the insomnia. And in
disrupting the brain, and serving as a stressor itself, sleep loss
renders people even more neurobiologically vulnerable to depression and
precipitates onset of episodes.

Further, insomnia can wreak havoc with a person's capacity to cope
with stressors at home, on the job, or in social life. The sense of
feeling "out of control" can generate feelings of helplessness. And these
negative feelings may spread, dredging up negative memories and
amplifying negative thoughts, creating the cloud of pessimism that the
depressed typically dwell under.

Perlis believes that behavioral treatment specifically aimed at
curbing the insomnia of depression may rout the entire disorder.
Behavioral treatment during periods of remission may keep full-blown
depression at bay. But even in frank depressive episodes, behavioral
treatment targeted specifically at the insomnia may hasten recovery. And
cognitive-behavioral therapy of insomnia may be a way to augment standard
treatments of depression

"Maybe we can protect people by paying attention to their
insomnia," says Perlis. "If it is an unleashing factor, perhaps if we get
rid of the insomnia we can get rid of the depression risk."