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.
In his most recent study, published in the April issue of The American Journal of Psychiatry, Krishnan suggested that the damage from lesions may cause depression either by means of directly disrupting the circuits that regulate mood, or by disrupting the serotonin and norepinephrine circuits that regulate this system. Additional functional imaging studies are underway to pinpoint the precise method of damage, he said.