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DURHAM, N.C. -- They were depressed, but there was little to
illuminate why. There was no family history of depression, no
previous bouts of sadness, no obvious stressors and not a
single overt physical sign that would link them to the
multitude of depressed adults nationwide. These elderly
patients had only one apparent marker -- strange lesions in the
brain's frontal lobe detected through magnetic resonance
imaging -- that would lead doctors toward the eventual cause of
their symptoms.

It wasn't the first time Dr. Ranga Krishnan had noticed
them. In fact, so common were these black holes or "lacunes" in
the basal ganglia of older patients that they were widely
assumed to be normal indicators of the aging brain, the Duke
University Medical Center psychiatrist said.

Krishnan, however, believed otherwise. An expert in senile
dementia and depression, Krishnan was keenly attuned to the
subtle mood and cognitive changes that differentiated his
patients' seemingly similar conditions. So Krishnan probed
deeper, scrutinizing their medical histories and risk factors,
until he found a startling link: all the patients with brain
lesions had symptoms of both depression and heart disease.

Krishnan felt there was a link between the two.

"It's been quite well established that depression
contributes to heart disease – in fact, studies here have shown
that depressed patients have a 50 percent higher risk of
cardiac death than patients without depression," Krishnan said
in an interview. "But here we had evidence suggesting a two-way
street, with risk factors for heart disease influencing the
onset of depression in otherwise mentally healthy
patients."

While the link between the brain and the heart is certainly
not new, Krishnan's research is among the first in recent times
to describe the pathology of this little known condition --
which he named vascular depression -- and its potential
mechanisms of action.

Initially, he stumbled upon the notion while scanning the
literature for studies that would shed light on the strange
lesions. His interest was piqued when he came across
little-known German studies, dating back a hundred years, that
described similar lesions. Their apparent origins, to his great
interest, were small "silent" strokes in the brain -- events so
undetectable that the patient suffered no obvious motor,
cognitive or speech loss. The black lacunes, he determined,
were areas of the brain deprived of blood and thus oxygen --
vessels that had been cut off completely and had ceased to
function.

Because these strokes only occurred deep within the emotion
centers of the brain, doctors typically had been unable to
detect the subtle alterations in mood and cognition that happen
over time. The symptoms were so typical of age-related diseases
that determining their cause is nearly impossible without more
sophisticated testing, Krishnan said.

Armed with the latest imaging techniques that measure blood
flow in the brain, he embarked on a research journey to learn
how and why the strokes were occurring. In the patients who
exhibited the lesions, they also experienced restricted blood
flow in other vessels and arteries throughout the body.

"What we found among these patients were all the classical
risk factors for heart disease but none of the risk factors for
depression," he said "They all had a history of diabetes,
hypertension, clogged arteries, and many had undergone
angioplasty or bypass surgery. In other words, their
cardiovascular risk factors gave rise to their depression."
Krishnan labeled the condition vascular or "arteriosclerotic"
depression to connote the narrowing and eventual closure of
small blood vessels that resulted in the silent strokes.

So common is the condition that it accounts for 30 percent
to 40 percent of all depression in people over the age of 65.
Yet the data on vascular depression is so new -- only in the
past seven years has it gained prominence – that it isn't
readily understood nor is it recognized within the medical
community, Krishnan said.

What happens is more of a process than an event, researchers
say. Unlike a full blown stroke, which occurs outside the brain
when a large artery either bursts or is suddenly closed off,
the silent mini-strokes occur gradually, as the blood flow to
smaller vessels within the brain becomes increasingly
restricted by process of narrowing or clogging. That is the
same mechanism at work in the heart patients. But for reasons
unknown, the narrowing only occurs in the frontal or left areas
of the brain, where changes are likely to precipitate changes
in mood but little else.

And because the patients often have other medical
conditions, including some cognitive impairment and functional
disability, the subtle mood changes are often ignored or
overlooked, Krishnan said.

Once a diagnosis is made, vascular depression defies simple
treatment, in part because so little has been attempted. The
usual anti-depressants do not appear to be successful, perhaps
because the condition appears to be a biological alteration and
not a chemical one, or because the damage has reduced the
brain's ability to metabolize drugs.

Krishnan is hopeful that treatments to prevent vascular
depression could mirror those for managing heart disease,
including a low-fat, low-salt diet; blood pressure and
cholesterol medications; and surgical techniques to treat
atherosclerosis. But he says clinical studies are needed to
confirm that, and such therapy may not reverse existing
damage.

"Until the mechanism of damage is known, treatment cannot be
tailored to the unique needs of vascular depression patients,"
said Krishnan.