cross-posted

hi all

this is the most important finding
i've seen about clinical depression (cd) in years

let's kiss that old stigma goodbye so long yer history!

janet

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Decade of Work Shows Depression Is Physical

Bethesda, Md - Psychiatrist and brain imaging researcher Wayne C. Drevets,
MD, recalls a patient dealing with breast cancer and unrelated episodes of
major depression. The woman found it easier to talk about the cancer
because, Drevets said, "with the depression there was nothing tangible to
point to or explain to people, even herself."

It turns out that there is something tangible. A decade of unusually
collaborative research by Drevets and a number of other researchers
dramatically illustrates that chronic major depression is as physical as
diabetes or heart disease.

Dysfunctional metabolism and blood flow in the brain's emotional centers
mark two physical manifestations of the mental disorder. Charted with
magnetic resonance imaging and positron emission tomography scans, these
findings have been replicated in dozens of studies.

More recently, Drevets and colleagues have detailed even more startling
findings: certain brain regions shrink in volume by nearly 40% during
depressive episodes, losing gray matter, mainly glial cells (Nature.
1997;386:824-827).

Neurons in these "emotion zones" also change, by cropping dendritic
connections to other parts of the brain, in effect short-circuiting an
individual's ability to deal with strong negative feelings (Nat Med.
2001;7:541-547).

A decade of imaging research points to specific, possibly irreversible,
changes in brain structures during and after episodes of major depression.
Here, transverse PET scans illustrate a recent finding, that brain
structures in individuals at nadir of depression cannot properly listen to
the neurotransmitter serotonin (5-hydroxytryptamine [HT]).

A series of scans using a radioactive tracer synthesized at the University
of Pittsburgh uncovered marked deficiency in 5-HT type 1A receptor activity
in depressed individuals.

The most pronounced deficits were seen in brain areas critical to emotional
stability, including the mesiotemporal cortex (home of the amygdala and the
hippocampus) and the midbrain raphe nucleus, which is densely packed with
serotonin-producing neurons (Biol Psychiatry. 1999;46:1375-1387).

Current antidepressant drugs, such as selective serotonin reuptake
inhibitors, appear to compensate for this effect in depressed individuals.

Other reports from this realm - namely, that these changes tend to persist
- explode the myth that people with serious depression "can just snap back
out of it," said Drevets, who is chief, Section on Neuroimaging in Mood and
Anxiety Disorders, Mood and Anxiety Disorders Program, at the National
Institute of Mental Health, during a recent "Director's Seminar Series"
talk here at the National Institutes of Health.

"It may be that ... it's not good enough to just 'tough it out,' avoid
treatment, and just hope for it to go away. You may be doing damage to some
structures."

AMYGDALA ABNORMALITIES

In particular, researchers describe physical abnormalities and functional
problems in the amygdala, part of the limbic system, and in the orbital
prefrontal cortex, a network above the eyes that receives signals from the
senses and helps regulate emotions.

While other areas of the brain have been implicated in depression, much
research has focused on these two, which together help orchestrate emotions
and subsequent behavior via a tangled web of connections with other vital
brain areas.

The amygdala plays a particularly stellar role in assigning emotional
significance to stimuli.

Monkeys with intentionally placed lesions in the amygdala, as well as
people with naturally occurring ones, cannot recognize facial expressions;
happy, sad, fearful, or ecstatic faces all look the same to them (Nature.
1994;372:669-672).

Electrical stimulation of the amygdala provokes strong reactions, instantly
triggering vivid recall of emotionally charged life events (Cortex.
1985;21:7-24).

And as shown in a well-known series of experiments by Antonio Damasio, MD,
PhD, at the University of Iowa College of Medicine, Iowa City, the amygdala
lights up with activity after mentally healthy individuals see a fearful or
sad face (Neuropsychologia. 1999;37:1111-1117).

In depressed individuals, these reactions are more pronounced, as seen on
various types of brain scans.

The amygdala may even get stuck in an overactive state, as it consumes more
glucose (a general sign of brain activity) in chronically depressed
patients than in controls (Pharmacol Biochem Behav. 2002;71:431-447).

Drevets said this hyperactivity apparently triggers symptoms via the
amygdala's extensive links with other parts of the brain, which originate
in a dense pack of output neurons called the central outflow nucleus.

"You can get a good idea of what depression syndrome looks like by going
through the list of what's impacted by [the central outflow] nucleus," said
Drevets, ticking off an inventory of symptoms including social withdrawal,
slowed metabolism, inactivity, decreased motivation, gastrointestinal
disturbances, and wakefulness in the middle of the night.

ROLE OF ORBITAL CORTEX

After the amygdala generates a strong emotion and the accompanying
autonomic reactions - say, fear followed by perspiration, tachycardia, and
a spike of adrenalin - the nearby orbital cortex keeps these mental and
physical manifestations from spiraling out of control.

It does this via its own network of connections, which stretch into nearly
all of the brain regions linked to the amygdala.

Together, the two areas comprise the yang (orbital cortex) and yin
(amygdala) of emotional responses, the existence of which were elucidated
5000 years ago in the founding text of traditional Chinese medicine, The
Yellow Emperor's Classic of Medicine: "Yang stands for peace and serenity;
Yin stands for confusion and turmoil. . . ." (Ebrey P. Chinese
Civilization: A Sourcebook. 2nd ed. New York, NY: Free Press; 1993:77).

Or as Drevets put it, "The more you activate your orbital cortex, the less
depressed you feel. The more you activate your amygdala, the more depressed
you feel."

Studies on healthy individuals in various emotional states, for example,
from the verge of tears to delighted, confirm the seesaw effect.

Curiously, though, imaging studies show that depressed individuals do have
more orbital cortex activity than healthy controls; it looks as if the area
is straining to suppress the emotional sparks thrown off by the amygdala.

Add that finding to the pathologic data that show the orbital cortex to be
shrunken in those who are depressed and "you get a sense that [the orbital
cortex] may not be working right," said Drevets.

"So, after looking at all of the data, the hypothesis is that dysfunction
of this area, rather than too much or too little activity, is responsible
for the depression."

More generally, these findings hold for other involved areas of the brain.

The regions responsible for regulating emotion have lost glial cells and
dendritic connections, rendering them dysfunctional.

In contrast, the regions that generate or express emotion are uninhibited
and overactive.

"ALL IN THE HEAD"

Exactly how or why these physical changes occur is unknown.

Most patients in imaging studies of major depression come from families
with a history of the disorder.

This has led some brain researchers on a search for genes that heighten
risk through, perhaps, a hypersensitivity to certain hormones or other
stimuli.

What is known is that once a person has survived his or her first bout with
depression, more will likely follow.

Drevets thinks that the odds for repairing the brain damage decrease with
each episode, making treatment with antidepressants, most of which appear
to confer some neuroprotective benefits, even more crucial.

"You still have this concept floating around ... that people must have
deep-seated psychological problems that they aren't dealing with, that's
why they're depressed," he said during a phone interview. "Some clinicians
think that the medicines just mask the underlying problem."

An ever-growing number of research reports refutes that notion, at least
for those with a family history of major depression.

The recent evidence also supports clinical impressions that go back to
earlier times. Even Sigmund Freud, in his 1917 essay, Mourning and
Melancholia, noted that some forms of depression suggest "somatic rather
than psychogenic affections."

The new brain imaging research thus gives a very different meaning to the
idea that the disorder is "all in the head."


Brian Vastag
2002 American Medical Association. All rights reserved.
http://jama.ama-assn.org/issues/v287n14/ffull/jmn0410-1.html

janet paterson: an akinetic rigid subtype, albeit perky, parky
pd: 55/41/37 cd: 55/44/43 tel: 613 256 8340 email: [log in to unmask]
smail: 375 Country Street, Almonte, Ontario, Canada, K0A 1A0
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